2022
S, Afewerki; S, Vargas Harb; T, Domingues Stocco; GU, Ruiz-Esparza; AO, Lobo
Polymers for surgical sutures Book Chapter
In: Advanced Technologies and Polymer Materials for Surgical Sutures, Elsevier, Cambridge, 2022.
@inbook{694631,
title = {Polymers for surgical sutures},
author = {Afewerki S and Vargas Harb S and Domingues Stocco T and Ruiz-Esparza GU and Lobo AO},
url = {https://www.elsevier.com/books/advanced-technologies-and-polymer-materials-for-surgical-sutures/thomas/978-0-12-819750-9},
year = {2022},
date = {2022-01-01},
booktitle = {Advanced Technologies and Polymer Materials for Surgical Sutures},
publisher = {Elsevier},
address = {Cambridge},
organization = {Elsevier},
abstract = {One of the biggest challenges within the medical practice is the innovation and improvements in technologies for the closure of wounds or sutures. The general technologies comprise physically perforating materials, for example, staples or sutures. These approaches have several limitations and challenges such as the risk of infections, cause continues pain, not always effective and in some cases can result in leakage at the site of closure. To overcome these challenges and limitations polymer-based sutures can be employed to hold body tissues together or ligate blood vessels, after a surgery or accidental injury. Depending on the damaged site, specific features are required to withstand the natural conditions of the body, but the utmost property for a suture material is its tensile strength, which can be tailored by the composition and thickness of the yarn. Aside the strength, other important properties to be considered are absorbability, sterility, high knot security, lack of allergic reaction, and ease of handling. In addition to these characteristics of biomaterials, in general, other criteria used for suture selection are based on the properties of the tissues involved, such as the specific healing rate; wound condition and general health of the patient, potential postoperative complications, personal preference and experience of the surgeon, and economic reasons. Among the extensive portfolio of materials currently available, synthetic and natural polymers have been the most frequently targeted.},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
One of the biggest challenges within the medical practice is the innovation and improvements in technologies for the closure of wounds or sutures. The general technologies comprise physically perforating materials, for example, staples or sutures. These approaches have several limitations and challenges such as the risk of infections, cause continues pain, not always effective and in some cases can result in leakage at the site of closure. To overcome these challenges and limitations polymer-based sutures can be employed to hold body tissues together or ligate blood vessels, after a surgery or accidental injury. Depending on the damaged site, specific features are required to withstand the natural conditions of the body, but the utmost property for a suture material is its tensile strength, which can be tailored by the composition and thickness of the yarn. Aside the strength, other important properties to be considered are absorbability, sterility, high knot security, lack of allergic reaction, and ease of handling. In addition to these characteristics of biomaterials, in general, other criteria used for suture selection are based on the properties of the tissues involved, such as the specific healing rate; wound condition and general health of the patient, potential postoperative complications, personal preference and experience of the surgeon, and economic reasons. Among the extensive portfolio of materials currently available, synthetic and natural polymers have been the most frequently targeted.
S, Afewerki; T, Domingues Stocco; A, Diniz Rosa Silva; A, Sales Aguiar Furtado; G, Fernandes Sousa; GU, Ruiz-Esparza; TJ, Webstere; FR, Marciano; M, Strømme; YS, Zhang; AO, Lobo
In vitro high-content tissue models to address precision medicine challenges Journal Article
In: Molecular Aspects of Medicine, 2022.
@article{692992,
title = {In vitro high-content tissue models to address precision medicine challenges},
author = {Afewerki S and Domingues Stocco T and Diniz Rosa Silva A and Sales Aguiar Furtado A and Fernandes Sousa G and Ruiz-Esparza GU and Webstere TJ and Marciano FR and Strømme M and Zhang YS and Lobo AO},
url = {https://www.sciencedirect.com/science/article/pii/S009829972200053X},
year = {2022},
date = {2022-01-01},
journal = {Molecular Aspects of Medicine},
abstract = {The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treat- ments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically repre- sentative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content in vitro tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treat- ments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically repre- sentative in vitro models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.
DO, Lopez-Cantu; X, Wang; H, Carrasco-Magallanes; S, Afewerki; X, Zhang; JV, Bonventre; GU, Ruiz-Esparza
From Bench to the Clinic: The Path to Translation of Nanotechnology-Enabled mRNA SARS-CoV-2 Vaccines Journal Article
In: Nano-Micro Letters, 2022.
@article{685737,
title = {From Bench to the Clinic: The Path to Translation of Nanotechnology-Enabled mRNA SARS-CoV-2 Vaccines},
author = {Lopez-Cantu DO and Wang X and Carrasco-Magallanes H and Afewerki S and Zhang X and Bonventre JV and Ruiz-Esparza GU},
url = {https://link.springer.com/article/10.1007/s40820-021-00771-8},
year = {2022},
date = {2022-01-01},
journal = {Nano-Micro Letters},
abstract = {During the last decades, the use of nanotechnology in medicine has effectively been translated to the design of drug delivery systems, nanostructured tissues, diagnostic platforms, and novel nanomaterials against several human diseases and infectious pathogens. Nanotechnology-enabled vaccines have been positioned as solutions to mitigate the pandemic outbreak caused by the novel pathogen severe acute respiratory syndrome coronavirus 2. To fast-track the development of vaccines, unprecedented industrial and academic collaborations emerged around the world, resulting in the clinical translation of effective vaccines in less than one year. In this article, we provide an overview of the path to translation from the bench to the clinic of nanotechnology-enabled messenger ribonucleic acid vaccines and examine in detail the types of delivery systems used, their mechanisms of action, obtained results during each phase of their clinical development and their regulatory approval process. We also analyze how nanotechnology is impacting global health and economy during the COVID-19 pandemic and beyond.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During the last decades, the use of nanotechnology in medicine has effectively been translated to the design of drug delivery systems, nanostructured tissues, diagnostic platforms, and novel nanomaterials against several human diseases and infectious pathogens. Nanotechnology-enabled vaccines have been positioned as solutions to mitigate the pandemic outbreak caused by the novel pathogen severe acute respiratory syndrome coronavirus 2. To fast-track the development of vaccines, unprecedented industrial and academic collaborations emerged around the world, resulting in the clinical translation of effective vaccines in less than one year. In this article, we provide an overview of the path to translation from the bench to the clinic of nanotechnology-enabled messenger ribonucleic acid vaccines and examine in detail the types of delivery systems used, their mechanisms of action, obtained results during each phase of their clinical development and their regulatory approval process. We also analyze how nanotechnology is impacting global health and economy during the COVID-19 pandemic and beyond.
2021
J, Hernandez; X, Wang; M, Vazquez-Segoviano; MF, Sobral-Reyes; A, Moran-Horowich; M, Sundberg; M, Lopez-Marfil; DO, Lopez-Cantu; C, Probst; GU, Ruiz-Esparza; K, Giannikou; E, Henske; D, Kwiatkowski; M, Sahin; DR, Lemos
A Tissue-Bioengineering Strategy for Modeling Rare Human Kidney Diseases In Vivo Journal Article
In: Nature Communications, 2021.
@article{683684,
title = {A Tissue-Bioengineering Strategy for Modeling Rare Human Kidney Diseases In Vivo},
author = {Hernandez J and Wang X and Vazquez-Segoviano M and Sobral-Reyes MF and Moran-Horowich A and Sundberg M and Lopez-Marfil M and Lopez-Cantu DO and Probst C and Ruiz-Esparza GU and Giannikou K and Henske E and Kwiatkowski D and Sahin M and Lemos DR},
url = {https://www.nature.com/articles/s41467-021-26596-y},
year = {2021},
date = {2021-01-01},
journal = {Nature Communications},
abstract = {The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2-/- hiPSCs but not from isogenic TSC2+/- or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2-/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2-/- hiPSCs but not from isogenic TSC2+/- or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2-/- renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.
GU, Ruiz-Esparza; X, Wang; X, Zhang; S, Jimenez-Vazquez; L, Diaz-Gomez; AM, Lavoie; S, Afewerki; A, Fuentes; R, Parra-Saldivar; N, Jiang; N, Annabi; B, Saleh; AK, Yetisen; A, Sheikhi; TH, Jozefiak; SR, Shin; N, Dong; A, Khademhosseini
Nanoengineered Shear-thinning Hydrogel Barrier for Preventing Postoperative Adhesions Journal Article
In: Nano-Micro Letters, 2021.
@article{570366,
title = {Nanoengineered Shear-thinning Hydrogel Barrier for Preventing Postoperative Adhesions},
author = {Ruiz-Esparza GU and Wang X and Zhang X and Jimenez-Vazquez S and Diaz-Gomez L and Lavoie AM and Afewerki S and Fuentes A and Parra-Saldivar R and Jiang N and Annabi N and Saleh B and Yetisen AK and Sheikhi A and Jozefiak TH and Shin SR and Dong N and Khademhosseini A},
url = {https://link.springer.com/article/10.1007/s40820-021-00712-5},
year = {2021},
date = {2021-01-01},
journal = {Nano-Micro Letters},
abstract = {More than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
More than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.
A, Mier; I, Maffucci; F, Merlier; E, Prost; E, Montagna; GU, Ruiz-Esparza; JV, Bonventre; PK, Dhal; B, Tse Sum Bui; P, Sakhaii; K, Haupt
In: Angewandte Chemie International Edition, 2021.
@article{678653,
title = {Molecularly Imprinted Polymer Nanogels for Protein Recognition: Direct Proof of Specific Binding Sites by Solution STD and WaterLOGSY NMR Spectroscopies},
author = {Mier A and Maffucci I and Merlier F and Prost E and Montagna E and Ruiz-Esparza GU and Bonventre JV and Dhal PK and Tse Sum Bui B and Sakhaii P and Haupt K},
url = {https://onlinelibrary.wiley.com/doi/10.1002/anie.202106507},
year = {2021},
date = {2021-01-01},
journal = {Angewandte Chemie International Edition},
abstract = {Molecularly imprinted polymers (MIPs) are tailor-made synthetic antibodies possessing specific binding cavities designed for a target molecule. Currently, MIPs for protein targets are synthesized by imprinting a short surface-exposed fragment of the protein, called epitope or antigenic determinant. However, finding the epitope par excellence that will yield a peptide ‘synthetic antibody’ cross-reacting exclusively with the protein from which it is derived, is not easy. We propose a computer-based rational approach to unambiguously identify the ‘best’ epitope candidate. Then, using Saturation Transfer Difference (STD) and WaterLOGSY NMR spectroscopies, we prove the existence of specific binding sites created by the imprinting of this peptide epitope in the MIP nanogel. The optimized MIP nanogel could bind the epitope and cognate protein with a high affinity and selectivity. The study was performed on Hepatitis A Virus Cell Receptor-1 protein, also known as KIM-1 and TIM-1, for its ubiquitous implication in numerous pathologies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Molecularly imprinted polymers (MIPs) are tailor-made synthetic antibodies possessing specific binding cavities designed for a target molecule. Currently, MIPs for protein targets are synthesized by imprinting a short surface-exposed fragment of the protein, called epitope or antigenic determinant. However, finding the epitope par excellence that will yield a peptide ‘synthetic antibody’ cross-reacting exclusively with the protein from which it is derived, is not easy. We propose a computer-based rational approach to unambiguously identify the ‘best’ epitope candidate. Then, using Saturation Transfer Difference (STD) and WaterLOGSY NMR spectroscopies, we prove the existence of specific binding sites created by the imprinting of this peptide epitope in the MIP nanogel. The optimized MIP nanogel could bind the epitope and cognate protein with a high affinity and selectivity. The study was performed on Hepatitis A Virus Cell Receptor-1 protein, also known as KIM-1 and TIM-1, for its ubiquitous implication in numerous pathologies.
X, Wang; Z, Liu; D, Sandoval-Salaiza; S, Afewerki; MG, Jimenez-Rodriguez; L, Sanchez-Melgar; G, Güemes-Aguilar; DG, Gonzalez-Sanchez; O, Noble; C, Lerma; R, Parra-Saldivar; DR, Lemos; GA, Llamas-Esperon; J, Shi; L, Li; AO, Lobo; AA, Fuentes-Baldemar; JV, Bonventre; N, Dong; GU, Ruiz-Esparza
Nanostructured Non-Newtonian Drug Delivery Barrier Prevents Postoperative Intrapericardial Adhesions Journal Article
In: ACS Applied Materials & Interfaces, 2021.
@article{678549,
title = {Nanostructured Non-Newtonian Drug Delivery Barrier Prevents Postoperative Intrapericardial Adhesions},
author = {Wang X and Liu Z and Sandoval-Salaiza D and Afewerki S and Jimenez-Rodriguez MG and Sanchez-Melgar L and Güemes-Aguilar G and Gonzalez-Sanchez DG and Noble O and Lerma C and Parra-Saldivar R and Lemos DR and Llamas-Esperon GA and Shi J and Li L and Lobo AO and Fuentes-Baldemar AA and Bonventre JV and Dong N and Ruiz-Esparza GU},
url = {https://pubs.acs.org/doi/abs/10.1021/acsami.0c20084},
year = {2021},
date = {2021-01-01},
journal = {ACS Applied Materials & Interfaces},
abstract = {With the increasing volume of cardiovascular surgeries and the rising adoption rate of new methodologies that serve as a bridge to cardiac transplantation and that require multiple surgical interventions, the formation of postoperative intrapericardial adhesions has become a challenging problem that limits future surgical procedures, causes serious complications, and increases medical costs. To prevent this pathology, we developed a nanotechnology-based self-healing drug delivery hydrogel barrier composed of silicate nanodisks and polyethylene glycol with the ability to coat the epicardial surface of the heart without friction and locally deliver dexamethasone, an anti-inflammatory drug. After the fabrication of the hydrogel, mechanical characterization and responses to shear, strain, and recovery were analyzed, confirming its shear-thinning and self-healing properties. This behavior allowed its facile injection (5.75 ± 0.15 to 22.01 ± 0.95 N) and subsequent mechanical recovery. The encapsulation of dexamethasone within the hydrogel system was confirmed by 1H NMR, and controlled release for 5 days was observed. In vitro, limited cellular adhesion to the hydrogel surface was achieved, and its anti-inflammatory properties were confirmed, as downregulation of ICAM-1 and VCAM-1 was observed in TNF-α activated endothelial cells. In vivo, 1 week after administration of the hydrogel to a rabbit model of intrapericardial injury, superior efficacy was observed when compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune infiltration of CD3+ lymphocytes and CD68+ macrophages, as well as NF-κβ downregulation. We presented a novel nanostructured drug delivery hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after a surgical intervention.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
With the increasing volume of cardiovascular surgeries and the rising adoption rate of new methodologies that serve as a bridge to cardiac transplantation and that require multiple surgical interventions, the formation of postoperative intrapericardial adhesions has become a challenging problem that limits future surgical procedures, causes serious complications, and increases medical costs. To prevent this pathology, we developed a nanotechnology-based self-healing drug delivery hydrogel barrier composed of silicate nanodisks and polyethylene glycol with the ability to coat the epicardial surface of the heart without friction and locally deliver dexamethasone, an anti-inflammatory drug. After the fabrication of the hydrogel, mechanical characterization and responses to shear, strain, and recovery were analyzed, confirming its shear-thinning and self-healing properties. This behavior allowed its facile injection (5.75 ± 0.15 to 22.01 ± 0.95 N) and subsequent mechanical recovery. The encapsulation of dexamethasone within the hydrogel system was confirmed by 1H NMR, and controlled release for 5 days was observed. In vitro, limited cellular adhesion to the hydrogel surface was achieved, and its anti-inflammatory properties were confirmed, as downregulation of ICAM-1 and VCAM-1 was observed in TNF-α activated endothelial cells. In vivo, 1 week after administration of the hydrogel to a rabbit model of intrapericardial injury, superior efficacy was observed when compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune infiltration of CD3+ lymphocytes and CD68+ macrophages, as well as NF-κβ downregulation. We presented a novel nanostructured drug delivery hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after a surgical intervention.
X, Wang; GU, Ruiz-Esparza
A Nanostructured Non-Newtonian Drug Delivery Barrier Prevents Postoperative Intrapericardial Adhesions Proceedings
vol. 77, no. 18, 2021.
@proceedings{678828,
title = {A Nanostructured Non-Newtonian Drug Delivery Barrier Prevents Postoperative Intrapericardial Adhesions},
author = {Wang X and Ruiz-Esparza GU},
url = {https://www.jacc.org/doi/full/10.1016/S0735-1097%2821%2904623-4},
year = {2021},
date = {2021-01-01},
journal = {Journal of the American College of Cardiology},
volume = {77},
number = {18},
pages = {(Supplement_1) 3269},
abstract = {Background: With the increasing volume of cardiovascular surgeries and the adoption of new methodologies as a bridge to cardiac transplantation, the formation of postoperative intrapericardial adhesions limits future surgical procedures, causes serious complications, and increases medical costs. Currently, no technology specifically designed to prevent intrapericardial adhesions exists.
Methods: Rheological analysis of hydrogel compositions was performed by an AR-G2 rheometer. The injection force was quantified by a mechanical tester. The 1H-Nuclear Magnetic Resonance (NMR) analysis was tested to confirm the hydrogel components. The cytotoxicity and cell-material interaction of hydrogel compositions were evaluated with NIH 3T3 fibroblasts and mouse brain endothelial cells. Rabbit intrapericardial adhesions model was used to test the therapeutic efficacy of the hydrogel formulations in vivo.
Results: Mechanical characterization and hydrogel response to shear, strain, and recovery confirmed its shear-thinning and self-healing properties. This behavior allowed its facile injection and subsequent mechanical recovery. Dexamethasone hydrogel encapsulation and controlled release for 5 days was achieved. In vitro, biocompatibility and limited fibroblast adhesion to the hydrogel surface was observed, and its anti-inflammatory properties were confirmed. In vivo, after one week of administration to a rabbit model of intrapericardial injury, the hydrogel showed superior efficacy compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune response. The echocardiographic assessment showed normal cardiac function after hydrogel administration.
Conclusion: We present a novel nanostructured hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after surgical intervention. This technology significantly reduces adhesion formation, resulting in a promising approach that could improve surgical cardiovascular outcomes.},
keywords = {},
pubstate = {published},
tppubtype = {proceedings}
}
Background: With the increasing volume of cardiovascular surgeries and the adoption of new methodologies as a bridge to cardiac transplantation, the formation of postoperative intrapericardial adhesions limits future surgical procedures, causes serious complications, and increases medical costs. Currently, no technology specifically designed to prevent intrapericardial adhesions exists.
Methods: Rheological analysis of hydrogel compositions was performed by an AR-G2 rheometer. The injection force was quantified by a mechanical tester. The 1H-Nuclear Magnetic Resonance (NMR) analysis was tested to confirm the hydrogel components. The cytotoxicity and cell-material interaction of hydrogel compositions were evaluated with NIH 3T3 fibroblasts and mouse brain endothelial cells. Rabbit intrapericardial adhesions model was used to test the therapeutic efficacy of the hydrogel formulations in vivo.
Results: Mechanical characterization and hydrogel response to shear, strain, and recovery confirmed its shear-thinning and self-healing properties. This behavior allowed its facile injection and subsequent mechanical recovery. Dexamethasone hydrogel encapsulation and controlled release for 5 days was achieved. In vitro, biocompatibility and limited fibroblast adhesion to the hydrogel surface was observed, and its anti-inflammatory properties were confirmed. In vivo, after one week of administration to a rabbit model of intrapericardial injury, the hydrogel showed superior efficacy compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune response. The echocardiographic assessment showed normal cardiac function after hydrogel administration.
Conclusion: We present a novel nanostructured hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after surgical intervention. This technology significantly reduces adhesion formation, resulting in a promising approach that could improve surgical cardiovascular outcomes.
Methods: Rheological analysis of hydrogel compositions was performed by an AR-G2 rheometer. The injection force was quantified by a mechanical tester. The 1H-Nuclear Magnetic Resonance (NMR) analysis was tested to confirm the hydrogel components. The cytotoxicity and cell-material interaction of hydrogel compositions were evaluated with NIH 3T3 fibroblasts and mouse brain endothelial cells. Rabbit intrapericardial adhesions model was used to test the therapeutic efficacy of the hydrogel formulations in vivo.
Results: Mechanical characterization and hydrogel response to shear, strain, and recovery confirmed its shear-thinning and self-healing properties. This behavior allowed its facile injection and subsequent mechanical recovery. Dexamethasone hydrogel encapsulation and controlled release for 5 days was achieved. In vitro, biocompatibility and limited fibroblast adhesion to the hydrogel surface was observed, and its anti-inflammatory properties were confirmed. In vivo, after one week of administration to a rabbit model of intrapericardial injury, the hydrogel showed superior efficacy compared to a commercial adhesion barrier, as histological and immunohistochemical examination revealed reduced adhesion formation and minimal immune response. The echocardiographic assessment showed normal cardiac function after hydrogel administration.
Conclusion: We present a novel nanostructured hydrogel system with unique mechanical and biological properties that act synergistically to prevent cellular infiltration while providing local immunomodulation to protect the intrapericardial space after surgical intervention. This technology significantly reduces adhesion formation, resulting in a promising approach that could improve surgical cardiovascular outcomes.
S, Afewerki; N, Bassous; S, Vargas Harb; MAF, Corat; S, Maharjan; GU, Ruiz-Esparza; MMM, Paula; TJ, Webster; CR, Tim; B, Cruz Viana; D, Wang; X, Wang; FR, Marciano; AO, Lobo
Engineering multifunctional bactericidal nanofibers for abdominal hernia repair Journal Article
In: Communications Biology, vol. 4, 2021.
@article{678545,
title = {Engineering multifunctional bactericidal nanofibers for abdominal hernia repair},
author = {Afewerki S and Bassous N and Vargas Harb S and Corat MAF and Maharjan S and Ruiz-Esparza GU and Paula MMM and Webster TJ and Tim CR and Cruz Viana B and Wang D and Wang X and Marciano FR and Lobo AO},
url = {https://www.nature.com/articles/s42003-021-01758-2},
year = {2021},
date = {2021-01-01},
journal = {Communications Biology},
volume = {4},
abstract = {The engineering of multifunctional surgical bactericidal nanofibers with inherent suitable mechanical and biological properties, through facile and cheap fabrication technology, is a great challenge. Moreover, hernia, which is when organ is pushed through an opening in the muscle or adjacent tissue due to damage of tissue structure or function, is a dire clinical challenge that currently needs surgery for recovery. Nevertheless, post-surgical hernia complications, like infection, fibrosis, tissue adhesions, scaffold rejection, inflammation, and recurrence still remain important clinical problems. Herein, through an integrated electrospinning, plasma treatment and direct surface modification strategy, multifunctional bactericidal nanofibers were engineered showing optimal properties for hernia repair. The nanofibers displayed good bactericidal activity, low inflammatory response, good biodegradation, as well as optimal collagen-, stress fiber- and blood vessel formation and associated tissue ingrowth in vivo. The disclosed engineering strategy serves as a prominent platform for the design of other multifunctional materials for various biomedical challenges.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The engineering of multifunctional surgical bactericidal nanofibers with inherent suitable mechanical and biological properties, through facile and cheap fabrication technology, is a great challenge. Moreover, hernia, which is when organ is pushed through an opening in the muscle or adjacent tissue due to damage of tissue structure or function, is a dire clinical challenge that currently needs surgery for recovery. Nevertheless, post-surgical hernia complications, like infection, fibrosis, tissue adhesions, scaffold rejection, inflammation, and recurrence still remain important clinical problems. Herein, through an integrated electrospinning, plasma treatment and direct surface modification strategy, multifunctional bactericidal nanofibers were engineered showing optimal properties for hernia repair. The nanofibers displayed good bactericidal activity, low inflammatory response, good biodegradation, as well as optimal collagen-, stress fiber- and blood vessel formation and associated tissue ingrowth in vivo. The disclosed engineering strategy serves as a prominent platform for the design of other multifunctional materials for various biomedical challenges.
2020
S, Afewerki; X, Wang; GU, Ruiz-Esparza; C, Tai; X, Kong; S, Zhou; K, Welch; P, Huang; R, Bengtsson; C, Xu; M, Strømme
Combined Catalysis for Engineering Bioinspired, Lignin-Based, Long-Lasting, Adhesive, Self-Mending, Antimicrobial Hydrogels Journal Article
In: ACS Nano, 2020.
@article{678544,
title = {Combined Catalysis for Engineering Bioinspired, Lignin-Based, Long-Lasting, Adhesive, Self-Mending, Antimicrobial Hydrogels},
author = {Afewerki S and Wang X and Ruiz-Esparza GU and Tai C and Kong X and Zhou S and Welch K and Huang P and Bengtsson R and Xu C and Strømme M},
url = {https://pubs.acs.org/doi/abs/10.1021/acsnano.0c06346},
year = {2020},
date = {2020-01-01},
journal = {ACS Nano},
abstract = {The engineering of multifunctional biomaterials using a facile sustainable methodology that follows the principles of green chemistry is still largely unexplored but would be very beneficial to the world. Here, the employment of catalytic reactions in combination with biomass-derived starting materials in the design of biomaterials would promote the development of eco-friendly technologies and sustainable materials. Herein, we disclose the combination of two catalytic cycles (combined catalysis) comprising oxidative decarboxylation and quinone-catechol redox catalysis for engineering lignin-based multifunctional antimicrobial hydrogels. The bioinspired design mimics the catechol chemistry employed by marine mussels in nature. The resultant multifunctional sustainable hydrogels (1) are robust and elastic, (2) have strong antimicrobial activity, (3) are adhesive to skin tissue and various other surfaces, and (4) are able to self-mend. A systematic characterization was carried out to fully elucidate and understand the facile and efficient catalytic strategy and the subsequent multifunctional materials. Electron paramagnetic resonance analysis confirmed the long-lasting quinone-catechol redox environment within the hydrogel system. Initial in vitrobiocompatibility studies demonstrated the low toxicity of the hydrogels. This proof-of-concept strategy could be developed into an important technological platform for the eco-friendly, bioinspired design of other multifunctional hydrogels and their use in various biomedical and flexible electronic applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The engineering of multifunctional biomaterials using a facile sustainable methodology that follows the principles of green chemistry is still largely unexplored but would be very beneficial to the world. Here, the employment of catalytic reactions in combination with biomass-derived starting materials in the design of biomaterials would promote the development of eco-friendly technologies and sustainable materials. Herein, we disclose the combination of two catalytic cycles (combined catalysis) comprising oxidative decarboxylation and quinone-catechol redox catalysis for engineering lignin-based multifunctional antimicrobial hydrogels. The bioinspired design mimics the catechol chemistry employed by marine mussels in nature. The resultant multifunctional sustainable hydrogels (1) are robust and elastic, (2) have strong antimicrobial activity, (3) are adhesive to skin tissue and various other surfaces, and (4) are able to self-mend. A systematic characterization was carried out to fully elucidate and understand the facile and efficient catalytic strategy and the subsequent multifunctional materials. Electron paramagnetic resonance analysis confirmed the long-lasting quinone-catechol redox environment within the hydrogel system. Initial in vitrobiocompatibility studies demonstrated the low toxicity of the hydrogels. This proof-of-concept strategy could be developed into an important technological platform for the eco-friendly, bioinspired design of other multifunctional hydrogels and their use in various biomedical and flexible electronic applications.
C, Adans-Dester; GU, Ruiz-Esparza; L, Williamson; P, Bonato
Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic? Journal Article
In: IEEE Open Journal of Engineering in Medicine and Biology, 2020.
@article{661550,
title = {Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?},
author = {Adans-Dester C and Ruiz-Esparza GU and Williamson L and Bonato P},
url = {https://ieeexplore.ieee.org/document/9162431},
year = {2020},
date = {2020-01-01},
journal = {IEEE Open Journal of Engineering in Medicine and Biology},
abstract = {Goal: The aim of the study herein reported was to review mobile health (mHealth) technologies and explore their use to monitor and mitigate the effects of the COVID-19 pandemic. Methods: A Task Force was assembled by recruiting individuals with expertise in electronic Patient-Reported Outcomes (ePRO), wearable sensors, and digital contact tracing technologies. Its members collected and discussed available information and summarized it in a series of reports. Results: The Task Force identified technologies that could be deployed in response to the COVID-19 pandemic and would likely be suitable for future pandemics. Criteria for their evaluation were agreed upon and applied to these systems. Conclusions: mHealth technologies are viable options to monitor COVID-19 patients and be used to predict symptom escalation for earlier intervention. These technologies could also be utilized to monitor individuals who are presumed non-infected and enable prediction of exposure to SARS-CoV-2, thus facilitating the prioritization of diagnostic testing.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Goal: The aim of the study herein reported was to review mobile health (mHealth) technologies and explore their use to monitor and mitigate the effects of the COVID-19 pandemic. Methods: A Task Force was assembled by recruiting individuals with expertise in electronic Patient-Reported Outcomes (ePRO), wearable sensors, and digital contact tracing technologies. Its members collected and discussed available information and summarized it in a series of reports. Results: The Task Force identified technologies that could be deployed in response to the COVID-19 pandemic and would likely be suitable for future pandemics. Criteria for their evaluation were agreed upon and applied to these systems. Conclusions: mHealth technologies are viable options to monitor COVID-19 patients and be used to predict symptom escalation for earlier intervention. These technologies could also be utilized to monitor individuals who are presumed non-infected and enable prediction of exposure to SARS-CoV-2, thus facilitating the prioritization of diagnostic testing.
S, Afewerki; GU, Ruiz-Esparza; AO, Lobo
Antimicrobial Electrospun Materials Book Chapter
In: Electrospun Materials and Their Allied Applications, pp. 243-264, John Wiley & Sons, 2020.
@inbook{652073,
title = {Antimicrobial Electrospun Materials},
author = {Afewerki S and Ruiz-Esparza GU and Lobo AO},
url = {https://books.google.com/books?hl=en&lr=&id=SFTdDwAAQBAJ&oi=fnd&pg=PA243&ots=pvGM_IElqs&sig=JButa2QifvGeAGApf1vKmnjuaig$#$v=onepage&q&f=false},
year = {2020},
date = {2020-01-01},
booktitle = {Electrospun Materials and Their Allied Applications},
pages = {243-264},
publisher = {John Wiley & Sons},
organization = {John Wiley & Sons},
abstract = {The fast-growing public health awareness and concern of the devastating problems with bacterial infections and the mounting resistance of bacteria to conventional antibiotic treatments have made this theme the top concern. At the same time the problem will not be solved through solely inventions of antimicrobial materials preventing the prevalence of bacteria resistance. Nevertheless, the fabrication and design of these materials are highly important to find its translational applications in our daily life. In this context, electrospun materials with their inimitable advantages and facile production make them a suitable candidate for various applications. The electrospinning technology represents a versatile and facile approach for the construction of ultrathin electrospun fibers from various materials. Then, it allows the fabrication of electrospun fibers with various and controlled dimensions such as nanosized fibers which have gained significant attention due to their valuable properties such as high surface area, large porosity, and lightweight. Through the combined electrospinning and antimicrobial material employment, a very powerful, robust, and vital strategy for engineered material can be generated. These materials can be employed in many areas such as healthcare (eg, tissue repair, drug delivery, and wound healing), environmental application (eg, filters and membranes), energy applications (solar and fuels cells), and in protecting clothing for medical and chemical workers.},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
The fast-growing public health awareness and concern of the devastating problems with bacterial infections and the mounting resistance of bacteria to conventional antibiotic treatments have made this theme the top concern. At the same time the problem will not be solved through solely inventions of antimicrobial materials preventing the prevalence of bacteria resistance. Nevertheless, the fabrication and design of these materials are highly important to find its translational applications in our daily life. In this context, electrospun materials with their inimitable advantages and facile production make them a suitable candidate for various applications. The electrospinning technology represents a versatile and facile approach for the construction of ultrathin electrospun fibers from various materials. Then, it allows the fabrication of electrospun fibers with various and controlled dimensions such as nanosized fibers which have gained significant attention due to their valuable properties such as high surface area, large porosity, and lightweight. Through the combined electrospinning and antimicrobial material employment, a very powerful, robust, and vital strategy for engineered material can be generated. These materials can be employed in many areas such as healthcare (eg, tissue repair, drug delivery, and wound healing), environmental application (eg, filters and membranes), energy applications (solar and fuels cells), and in protecting clothing for medical and chemical workers.
AIS, Morais; X, Wang; EG, Vieira; BC, Viana; EC, Silva-Filho; JA, Osajima; S, Afewerki; MAF, Corat; HS, Silva; FR, Marciano; GU, Ruiz-Esparza; TD, Stocco; MMM, Paula; AO, Lobo
Electrospraying Oxygen-Generating Microparticles for Tissue Engineering Applications Journal Article
In: International Journal of Nanomedicine, vol. 2020, no. 15, pp. 1173-1186, 2020.
@article{648547,
title = {Electrospraying Oxygen-Generating Microparticles for Tissue Engineering Applications},
author = {Morais AIS and Wang X and Vieira EG and Viana BC and Silva-Filho EC and Osajima JA and Afewerki S and Corat MAF and Silva HS and Marciano FR and Ruiz-Esparza GU and Stocco TD and Paula MMM and Lobo AO},
url = {https://www.dovepress.com/electrospraying-oxygen-generating-microparticles-for-tissue-engineerin-peer-reviewed-article-IJN},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Nanomedicine},
volume = {2020},
number = {15},
pages = {1173-1186},
abstract = {Background: The facile preparation of oxygen-generating microparticles (M) consisting of Polycaprolactone (PCL), Pluronic F-127, and calcium peroxide (CPO) (PCL-F-CPO-M) fabricated through an electrospraying process is disclosed. The biological study confirmed the positive impact from the oxygen-generating microparticles on the cell growth with high viability. The presented technology could work as a prominent tool for various tissue engineering and biomedical applications.Methods: The oxygen-generated microparticles fabricated through electrospraying processes were thoroughly characterization through various methods such as X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) analysis, and scanning electron microscopy (SEM)/SEM-Energy Dispersive Spectroscopy (EDS) analysis.Results: The analyses confirmed the presence of the various components and the porous structure of the microparticles. Spherical shape with spongy characteristic microparticles were obtained with negative charge surface (ζ = – 16.9) and a size of 17.00 ± 0.34 μm. Furthermore, the biological study performed on rat chondrocytes demonstrated good cell viability and the positive impact of increasing the amount of CPO in the PCL-F-CPO-M.Conclusion: This technological platform could work as an important tool for tissue engineering due to the ability of the microparticles to release oxygen in a sustained manner for up to 7 days with high cell viability.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The facile preparation of oxygen-generating microparticles (M) consisting of Polycaprolactone (PCL), Pluronic F-127, and calcium peroxide (CPO) (PCL-F-CPO-M) fabricated through an electrospraying process is disclosed. The biological study confirmed the positive impact from the oxygen-generating microparticles on the cell growth with high viability. The presented technology could work as a prominent tool for various tissue engineering and biomedical applications.Methods: The oxygen-generated microparticles fabricated through electrospraying processes were thoroughly characterization through various methods such as X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) analysis, and scanning electron microscopy (SEM)/SEM-Energy Dispersive Spectroscopy (EDS) analysis.Results: The analyses confirmed the presence of the various components and the porous structure of the microparticles. Spherical shape with spongy characteristic microparticles were obtained with negative charge surface (ζ = – 16.9) and a size of 17.00 ± 0.34 μm. Furthermore, the biological study performed on rat chondrocytes demonstrated good cell viability and the positive impact of increasing the amount of CPO in the PCL-F-CPO-M.Conclusion: This technological platform could work as an important tool for tissue engineering due to the ability of the microparticles to release oxygen in a sustained manner for up to 7 days with high cell viability.
S, Afewerki; Bassous, N; Harb, S; C, Palo-Nieto; GU, Ruiz-Esparza; FR, Marciano; TJ, Webster; AO, Lobo
Advances in Antimicrobial and Osteoinductive Biomaterials Book Chapter
In: Racing for the Surface: Antimicrobial and Interface Tissue Engineering, pp. 3-34, Springer, 2020.
@inbook{652074,
title = {Advances in Antimicrobial and Osteoinductive Biomaterials},
author = {Afewerki S and N Bassous and S Harb and Palo-Nieto C and Ruiz-Esparza GU and Marciano FR and Webster TJ and Lobo AO},
url = {https://link.springer.com/chapter/10.1007/978-3-030-34471-9_1},
year = {2020},
date = {2020-01-01},
booktitle = {Racing for the Surface: Antimicrobial and Interface Tissue Engineering},
pages = {3-34},
publisher = {Springer},
organization = {Springer},
abstract = {The enormous growing problem with antibiotic resistance in pathogenic microbes is one of the greatest threats we are facing today. In the context of orthopedic applications, infections also lead to the limited healing ability of infected and defected bone. Generally, these problems are treated with a load of antibiotics or surgical intervention. Therefore, having antibacterial properties integrated with a biomaterial would reduce the time of healing and treatment, amount of antibiotic needed, and total cost. Currently, there exists several strategies and materials with the potential of tackling these challenges. Some materials with antibacterial properties currently employed are silver nanoparticles (AgNPs), cerium oxide nanoparticles (CeO2NPs), selenium nanoparticles (SeNPs), copper nanoparticles (CuNPs), antimicrobial peptides (AMPs), biopolymers (such as chitosan), and carbon nanostructures. On the other hand, osteoinductive and osteoconductive materials are important to promote bone healing and regeneration. Within this framework, materials which have been employed widely are bioactive glasses (BG), calcium phosphates (CaPs) (e.g., hydroxyapatite (HA), tricalcium β-phosphate (β-TCP), and biphasic calcium phosphate (BCP)), peptides, growth factors, and other elements (e.g., magnesium (Mg), zinc (Zn), strontium (Sr), silicon (Si), selenium (Se), and Cu, to name a few). Some of the current technological solutions that have been employed are, for instance, the use of a co-delivery system, where both the antibacterial and the osteoinducing agents are delivered from the same delivery system. However, this approach requires overcoming challenges with local delivery in a sustained and prolonged way, thus avoiding tissue toxicity. To address these challenges and promote novel biomaterials with dual action, sophisticated thinking and approaches have to be employed. For this, it is of the utmost importance to have a solid fundamental understanding of current technologies, bacteria behavior and response to treatments, and also a correlation between the material of use, the host tissue and bacteria. We hope by highlighting these aspects, we will promote the invention of the next generation of smart biomaterials with dual action ability to both inhibit infection and promote tissue growth.},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
The enormous growing problem with antibiotic resistance in pathogenic microbes is one of the greatest threats we are facing today. In the context of orthopedic applications, infections also lead to the limited healing ability of infected and defected bone. Generally, these problems are treated with a load of antibiotics or surgical intervention. Therefore, having antibacterial properties integrated with a biomaterial would reduce the time of healing and treatment, amount of antibiotic needed, and total cost. Currently, there exists several strategies and materials with the potential of tackling these challenges. Some materials with antibacterial properties currently employed are silver nanoparticles (AgNPs), cerium oxide nanoparticles (CeO2NPs), selenium nanoparticles (SeNPs), copper nanoparticles (CuNPs), antimicrobial peptides (AMPs), biopolymers (such as chitosan), and carbon nanostructures. On the other hand, osteoinductive and osteoconductive materials are important to promote bone healing and regeneration. Within this framework, materials which have been employed widely are bioactive glasses (BG), calcium phosphates (CaPs) (e.g., hydroxyapatite (HA), tricalcium β-phosphate (β-TCP), and biphasic calcium phosphate (BCP)), peptides, growth factors, and other elements (e.g., magnesium (Mg), zinc (Zn), strontium (Sr), silicon (Si), selenium (Se), and Cu, to name a few). Some of the current technological solutions that have been employed are, for instance, the use of a co-delivery system, where both the antibacterial and the osteoinducing agents are delivered from the same delivery system. However, this approach requires overcoming challenges with local delivery in a sustained and prolonged way, thus avoiding tissue toxicity. To address these challenges and promote novel biomaterials with dual action, sophisticated thinking and approaches have to be employed. For this, it is of the utmost importance to have a solid fundamental understanding of current technologies, bacteria behavior and response to treatments, and also a correlation between the material of use, the host tissue and bacteria. We hope by highlighting these aspects, we will promote the invention of the next generation of smart biomaterials with dual action ability to both inhibit infection and promote tissue growth.
2019
S, Afewerki; N, Bassous; S, Harb; C, Palo-Nieto; GU, Ruiz-Esparza; FR, Marciano; TJ, Webster; AS, Aguiar Furtado; AO, Lobo
Advances in Dual Functional Antimicrobial and Osteoinductive Biomaterials for Orthopedic Applications Journal Article
In: Nanomedicine: Nanotechnology, Biology and Medicine, 2019.
@article{645752,
title = {Advances in Dual Functional Antimicrobial and Osteoinductive Biomaterials for Orthopedic Applications},
author = {Afewerki S and Bassous N and Harb S and Palo-Nieto C and Ruiz-Esparza GU and Marciano FR and Webster TJ and Aguiar Furtado AS and Lobo AO},
url = {https://www.sciencedirect.com/science/article/abs/pii/S1549963419302278},
year = {2019},
date = {2019-01-01},
journal = {Nanomedicine: Nanotechnology, Biology and Medicine},
abstract = {A vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prothesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A vast growing problem in orthopaedic medicine is the increase of clinical cases with antibiotic resistant pathogenic microbes, which is predicted to cause higher mortality than all cancers combined by 2050. Bone infectious diseases limit the healing ability of tissues and increase the risk of future injuries due to pathologic tissue remodelling. The traditional treatment for bone infections has several drawbacks and limitations, such as lengthy antibiotic treatment, extensive surgical interventions, and removal of orthopaedic implants and/or prothesis, all of these resulting in long-term rehabilitation. This is a huge burden to the public health system resulting in increased healthcare costs. Current technologies e.g. co-delivery systems, where antibacterial and osteoinductive agents are delivered encounter challenges such as site-specific delivery, sustained and prolonged release, and biocompatibility. In this review, these aspects are highlighted to promote the invention of the next generation biomaterials to prevent and/or treat bone infections and promote tissue regeneration.
2018
JH, Ramirez-Leyva; G, Vitale; A, Hethnawi; A, Hassan; MJ, Perez Zurita; GU, Ruiz-Esparza; NN, Nassar
In: ACS Applied Nano Materials, 2018.
@article{609470,
title = {Mechanism of hierarchical porosity development in hexagonal boron nitride nanocrystalline microstructures for biomedical and industrial applications},
author = {Ramirez-Leyva JH and Vitale G and Hethnawi A and Hassan A and Perez Zurita MJ and Ruiz-Esparza GU and Nassar NN},
url = {https://cdn-pubs.acs.org/doi/10.1021/acsanm.8b00765},
year = {2018},
date = {2018-01-01},
journal = {ACS Applied Nano Materials},
abstract = {A well-known ceramic material, hexagonal boron nitride (h-BN) has a number of unique properties, including structural and porosity features, that make it suitable for a wide range of industrial applications. Hierarchical porosity and high specific surface area are desirable properties for adsorption processes such as water and air cleaning, hydrogen storage and drug delivery. These characteristics could be controlled and optimized by synthesis procedures, however this process requires an understanding of the factors and mechanisms of nanocrystalline h-BN porosity development and textural properties. In this study we demonstrate that hierarchical porosity displays evidence of the consecutive h-BN synthesis steps and thermal decomposition of intermediants. In addition, evidence shows that h-BN nanosheets can be folded as a result of Van der Waals forces interactions at elevated temperatures, which is corroborated by a computational modeling. Biocompatibility of the prepared h-BN was also evaluated to confirm the non-toxicity of the material.The results of this research could aid in the optimization and scaling up of an environmentally friendly h-BN synthesis process, and assist in the development of new methods for the production of h-BN at a commercial level.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A well-known ceramic material, hexagonal boron nitride (h-BN) has a number of unique properties, including structural and porosity features, that make it suitable for a wide range of industrial applications. Hierarchical porosity and high specific surface area are desirable properties for adsorption processes such as water and air cleaning, hydrogen storage and drug delivery. These characteristics could be controlled and optimized by synthesis procedures, however this process requires an understanding of the factors and mechanisms of nanocrystalline h-BN porosity development and textural properties. In this study we demonstrate that hierarchical porosity displays evidence of the consecutive h-BN synthesis steps and thermal decomposition of intermediants. In addition, evidence shows that h-BN nanosheets can be folded as a result of Van der Waals forces interactions at elevated temperatures, which is corroborated by a computational modeling. Biocompatibility of the prepared h-BN was also evaluated to confirm the non-toxicity of the material.The results of this research could aid in the optimization and scaling up of an environmentally friendly h-BN synthesis process, and assist in the development of new methods for the production of h-BN at a commercial level.
N, Annabi; Y, Zhang; A, Assmann; E, Shirzaei Sani; A, Vegh; G, Cheng; B, Dehghani; GU, Ruiz-Esparza; X, Wang; AS, Lassaletta; S, Gangadharan; AS, Weiss; A, Khademhosseini
Engineering a highly elastic and adhesive surgical sealant Conference
8th World Congress of Biomechanics, Dublin, Ireland, 2018.
@conference{619451,
title = {Engineering a highly elastic and adhesive surgical sealant},
author = {Annabi N and Zhang Y and Assmann A and Shirzaei Sani E and Vegh A and Cheng G and Dehghani B and Ruiz-Esparza GU and Wang X and Lassaletta AS and Gangadharan S and Weiss AS and Khademhosseini A},
url = {https://app.oxfordabstracts.com/stages/123/programme-builder/submission/14213?backHref=/events/123/programme-builder/view/sort/programme-code},
year = {2018},
date = {2018-01-01},
booktitle = {8th World Congress of Biomechanics},
address = {Dublin, Ireland},
abstract = {Approximately 114 million surgical and procedure-based wounds occur annually worldwide, including 36 million from surgeries in the US. Post-operative reconnection of tissues is crucial for restoring adequate function and structure. Sutures, wires, and staples are widely used for this purpose. Despite their common use in the clinic, these methods exhibit limitations when being applied to fragile and soft tissues, especially if the sealing is intended to prevent liquid or air leakage against high pressure, as e.g. in vascular and lung surgeries. Various types of surgical materials have been used for sealing, and reconnecting tissues, or attaching devices to tissues. However, these biomaterials often suffer from low adhesion strength, insufficient mechanical stability and strength, cytotoxic degradation products, and weak performance in biological environments. Therefore, in this study we aimed to engineer a photocrosslinked and highly elastic sealant with tunable mechanical and adhesion properties using tropoelastin, as a genetically modified human protein. We tuned the degree of methacrylation of tropoelastin and prepolymer concentration to optimize the physical properties and adhesion strength of the methacryloyl-substituted tropoelastin (MeTro) hydrogel for sealing of elastic and soft tissues. Following ASTM standard tests, the MeTro hydrogels revealed superior adhesive strength and burst pressure values compared to the commercially available sealants. The subcutaneous implantation of the engineered MeTro hydrogels in rats exhibited minimal inflammatory host responses and slow biodegradation of sealant. The in vivo and ex vivo burst pressure resistance of bioengineered MeTro sealants was tested on lungs and arteries in small as well as translational large animal models. Our results proved MeTro sealant to effectively seal lung and artery leakages without the need for sutures or staples, presenting a significant improvement compared to the commercially available clinical sealants and sutures only. Combining these results, we envision that the engineered MeTro sealant has the potential to be commercialized due to its remarkable mechanical strength, biocompatibility, biodegradability and strong adhesion to the tissues without the need for suturing.},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
Approximately 114 million surgical and procedure-based wounds occur annually worldwide, including 36 million from surgeries in the US. Post-operative reconnection of tissues is crucial for restoring adequate function and structure. Sutures, wires, and staples are widely used for this purpose. Despite their common use in the clinic, these methods exhibit limitations when being applied to fragile and soft tissues, especially if the sealing is intended to prevent liquid or air leakage against high pressure, as e.g. in vascular and lung surgeries. Various types of surgical materials have been used for sealing, and reconnecting tissues, or attaching devices to tissues. However, these biomaterials often suffer from low adhesion strength, insufficient mechanical stability and strength, cytotoxic degradation products, and weak performance in biological environments. Therefore, in this study we aimed to engineer a photocrosslinked and highly elastic sealant with tunable mechanical and adhesion properties using tropoelastin, as a genetically modified human protein. We tuned the degree of methacrylation of tropoelastin and prepolymer concentration to optimize the physical properties and adhesion strength of the methacryloyl-substituted tropoelastin (MeTro) hydrogel for sealing of elastic and soft tissues. Following ASTM standard tests, the MeTro hydrogels revealed superior adhesive strength and burst pressure values compared to the commercially available sealants. The subcutaneous implantation of the engineered MeTro hydrogels in rats exhibited minimal inflammatory host responses and slow biodegradation of sealant. The in vivo and ex vivo burst pressure resistance of bioengineered MeTro sealants was tested on lungs and arteries in small as well as translational large animal models. Our results proved MeTro sealant to effectively seal lung and artery leakages without the need for sutures or staples, presenting a significant improvement compared to the commercially available clinical sealants and sutures only. Combining these results, we envision that the engineered MeTro sealant has the potential to be commercialized due to its remarkable mechanical strength, biocompatibility, biodegradability and strong adhesion to the tissues without the need for suturing.
J, Paez-Mayorga; G, Hernández-Vargas; GU, Ruiz-Esparza; HMN, Iqbal; X, Wang; YS, Zhang; R, Parra-Saldivar; A, Khademhosseini
Bioreactors for cardiac tissue engineering Journal Article
In: Advanced Healthcare Materials, 2018.
@article{562846,
title = {Bioreactors for cardiac tissue engineering},
author = {Paez-Mayorga J and Hernández-Vargas G and Ruiz-Esparza GU and Iqbal HMN and Wang X and Zhang YS and Parra-Saldivar R and Khademhosseini A},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.201701504},
year = {2018},
date = {2018-01-01},
journal = {Advanced Healthcare Materials},
abstract = {The advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate their natural counterparts. Heart disease, one of the leading causes of death in modern society, has attracted particular attention in the field of tissue engineering. To avoid incorrect prognosis of patients suffering from heart disease, or from adverse consequences of classical therapeutic approaches, as well as to address the shortage of heart donors, new solutions are urgently needed. Biotechnological advances in cardiac tissue engineering from a bioreactor perspective, in which recapitulation of functional, biochemical, and physiological characteristics of the cardiac tissue can be used to recreate its natural microenvironment, are reviewed. Detailed examples of functional and preclinical applications of engineered cardiac constructs and the state-of-the-art systems from a bioreactor perspective are provided. Finally, the current trends and future directions of the field for its translation to clinical settings are discussed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The advances in biotechnology, biomechanics, and biomaterials can be used to develop organ models that aim to accurately emulate their natural counterparts. Heart disease, one of the leading causes of death in modern society, has attracted particular attention in the field of tissue engineering. To avoid incorrect prognosis of patients suffering from heart disease, or from adverse consequences of classical therapeutic approaches, as well as to address the shortage of heart donors, new solutions are urgently needed. Biotechnological advances in cardiac tissue engineering from a bioreactor perspective, in which recapitulation of functional, biochemical, and physiological characteristics of the cardiac tissue can be used to recreate its natural microenvironment, are reviewed. Detailed examples of functional and preclinical applications of engineered cardiac constructs and the state-of-the-art systems from a bioreactor perspective are provided. Finally, the current trends and future directions of the field for its translation to clinical settings are discussed.
AK, Miri; D, Nieto; L, Iglesias; HG, Hosseinabadi; S, Maharjan; GU, Ruiz-Esparza; P, Khoshakhlagh; A, Manbachi; MR, Dokmeci; S, Chen; SR, Shin; YS, Zhang; A, Khademhosseini
Microfluidics-Enabled Multi-Material Maskless Stereolithographic Bioprinting Journal Article
In: Advanced Materials, 2018.
@article{605578,
title = {Microfluidics-Enabled Multi-Material Maskless Stereolithographic Bioprinting},
author = {Miri AK and Nieto D and Iglesias L and Hosseinabadi HG and Maharjan S and Ruiz-Esparza GU and Khoshakhlagh P and Manbachi A and Dokmeci MR and Chen S and Shin SR and Zhang YS and Khademhosseini A},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201800242},
year = {2018},
date = {2018-01-01},
journal = {Advanced Materials},
abstract = {A stereolithography-based bioprinting platform for multimaterial fabrication of heterogeneous hydrogel constructs is presented. Dynamic patterning by a digital micromirror device, synchronized by a moving stage and a microfluidic device containing four on/off pneumatic valves, is used to create 3D constructs. The novel microfluidic device is capable of fast switching between different (cell-loaded) hydrogel bioinks, to achieve layer-by-layer multimaterial bioprinting. Compared to conventional stereolithography-based bioprinters, the system provides the unique advantage of multimaterial fabrication capability at high spatial resolution. To demonstrate the multimaterial capacity of this system, a variety of hydrogel constructs are generated, including those based on poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacryloyl (GelMA). The biocompatibility of this system is validated by introducing cell-laden GelMA into the microfluidic device and fabricating cellularized constructs. A pattern of a PEGDA frame and three different concentrations of GelMA, loaded with vascular endothelial growth factor, are further assessed for its neovascularization potential in a rat model. The proposed system provides a robust platform for bioprinting of high-fidelity multimaterial microstructures on demand for applications in tissue engineering, regenerative medicine, and biosensing, which are otherwise not readily achievable at high speed with conventional stereolithographic biofabrication platforms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
A stereolithography-based bioprinting platform for multimaterial fabrication of heterogeneous hydrogel constructs is presented. Dynamic patterning by a digital micromirror device, synchronized by a moving stage and a microfluidic device containing four on/off pneumatic valves, is used to create 3D constructs. The novel microfluidic device is capable of fast switching between different (cell-loaded) hydrogel bioinks, to achieve layer-by-layer multimaterial bioprinting. Compared to conventional stereolithography-based bioprinters, the system provides the unique advantage of multimaterial fabrication capability at high spatial resolution. To demonstrate the multimaterial capacity of this system, a variety of hydrogel constructs are generated, including those based on poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacryloyl (GelMA). The biocompatibility of this system is validated by introducing cell-laden GelMA into the microfluidic device and fabricating cellularized constructs. A pattern of a PEGDA frame and three different concentrations of GelMA, loaded with vascular endothelial growth factor, are further assessed for its neovascularization potential in a rat model. The proposed system provides a robust platform for bioprinting of high-fidelity multimaterial microstructures on demand for applications in tissue engineering, regenerative medicine, and biosensing, which are otherwise not readily achievable at high speed with conventional stereolithographic biofabrication platforms.
2017
N, Annabi; A, Assmann; A, Vegh; M, Ghasemi-Rad; S, Bagherifard; G, Cheng; GU, Ruiz-Esparza; X, Wang; I, Noshadi; A, Lassaletta; S, Gangadharan; A, Khademhosseini
Engineering a highly elastic human protein-based sealant for surgical applications. Journal Article
In: Science Translational Medicine, vol. 9, no. 410, 2017.
@article{562836,
title = {Engineering a highly elastic human protein-based sealant for surgical applications.},
author = {Annabi N and Assmann A and Vegh A and Ghasemi-Rad M and Bagherifard S and Cheng G and Ruiz-Esparza GU and Wang X and Noshadi I and Lassaletta A and Gangadharan S and Khademhosseini A},
url = {http://stm.sciencemag.org/content/9/410/eaai7466},
year = {2017},
date = {2017-01-01},
journal = {Science Translational Medicine},
volume = {9},
number = {410},
abstract = {Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.
J, Leijten; J, Seo; K, Yue; G, Trujillo-de Santiago; A, Tamayol; GU, Ruiz-Esparza; SR, Shin; R, Sharifi; I, Noshadi; MM, Álvarez; YS, Zhang; A, Khademhosseini
Spatially and temporally controlled hydrogels for tissue engineering. Journal Article
In: Materials Science and Engineering: R: Reports, 2017.
@article{562831,
title = {Spatially and temporally controlled hydrogels for tissue engineering.},
author = {Leijten J and Seo J and Yue K and Trujillo-de Santiago G and Tamayol A and Ruiz-Esparza GU and Shin SR and Sharifi R and Noshadi I and Álvarez MM and Zhang YS and Khademhosseini A},
url = {http://www.sciencedirect.com/science/article/pii/S0927796X17300499},
year = {2017},
date = {2017-01-01},
journal = {Materials Science and Engineering: R: Reports},
abstract = {Recent years have seen tremendous advances in the field of hydrogel-based biomaterials. One of the most prominent revolutions in this field has been the integration of elements or techniques that enable spatial and temporal control over hydrogels’ properties and functions. Here, we critically review the emerging progress of spatiotemporal control over biomaterial properties towards the development of functional engineered tissue constructs. Specifically, we will highlight the main advances in the spatial control of biomaterials, such as surface modification, microfabrication, photo-patterning, and bioprinting, as well as advances in the temporal control of biomaterials, such as controlled release of molecules, photocleaving of proteins, and controlled hydrogel degradation. We believe that the development and integration of these techniques will drive the evolution of next-generation engineered tissues.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recent years have seen tremendous advances in the field of hydrogel-based biomaterials. One of the most prominent revolutions in this field has been the integration of elements or techniques that enable spatial and temporal control over hydrogels’ properties and functions. Here, we critically review the emerging progress of spatiotemporal control over biomaterial properties towards the development of functional engineered tissue constructs. Specifically, we will highlight the main advances in the spatial control of biomaterials, such as surface modification, microfabrication, photo-patterning, and bioprinting, as well as advances in the temporal control of biomaterials, such as controlled release of molecules, photocleaving of proteins, and controlled hydrogel degradation. We believe that the development and integration of these techniques will drive the evolution of next-generation engineered tissues.
A, Assmann; A, Vegh; M, Ghasemi-Rad; S, Bagherifard; G, Cheng; ES, Sani; GU, Ruiz-Esparza; I, Noshadi; AD, Lassaletta; S, Gangadharan; A, Tamayol; A, Khademhosseini; N, Annabi
A highly adhesive and naturally derived sealant. Journal Article
In: Biomaterials, 2017.
@article{562826,
title = {A highly adhesive and naturally derived sealant.},
author = {Assmann A and Vegh A and Ghasemi-Rad M and Bagherifard S and Cheng G and Sani ES and Ruiz-Esparza GU and Noshadi I and Lassaletta AD and Gangadharan S and Tamayol A and Khademhosseini A and Annabi N},
url = {http://www.sciencedirect.com/science/article/pii/S0142961217303964},
year = {2017},
date = {2017-01-01},
journal = {Biomaterials},
abstract = {Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration.
L, Elizondo-Montemayor; C, Silva-Platas; A, Torres-Quintanilla; C, Rodriguez-Lopez; GU, Ruiz-Esparza; E, Reyes-Mendoza; G, Garcia-Rivas
Association of Irisin Plasma Levels with Anthropometric Parameters in Children with Underweight, Normal Weight, Overweight, and Obesity. Journal Article
In: Biomed Research International, 2017.
@article{562821,
title = {Association of Irisin Plasma Levels with Anthropometric Parameters in Children with Underweight, Normal Weight, Overweight, and Obesity.},
author = {Elizondo-Montemayor L and Silva-Platas C and Torres-Quintanilla A and Rodriguez-Lopez C and Ruiz-Esparza GU and Reyes-Mendoza E and Garcia-Rivas G},
url = {https://www.hindawi.com/journals/bmri/2017/2628968/},
year = {2017},
date = {2017-01-01},
journal = {Biomed Research International},
abstract = {The correlations between irisin levels, physical activity, and anthropometric measurements have been extensively described in adults with considerable controversy, but little evidence about these relationships has been found in children. The objective of this study is to correlate the plasma levels of irisin in underweight, normal weight, overweight, and obese children with anthropometric parameters and physical activity levels. A cross-sample of 40 children was divided into the following groups on the basis of body mass index (BMI) percentile. The correlations of plasma irisin levels with physical activity, anthropometric, and metabolic measurements were determined. Plasma irisin levels (ng/mL) were lower for the underweight group (164.2 ± 5.95) than for the normal weight and obese groups (182.8 ± 5.58; ). Irisin levels correlated positively with BMI percentile (0.387), waist circumference (0.373), and fat-free mass (0.353; ), but not with body muscle mass (-0.027). After a multiple linear regression analysis, only BMI percentile (0.564; ) showed a positive correlation with irisin. Our results indicated no association with metabolic parameters. A negative correlation with physical activity was observed. Interrelationships among body components might influence irisin levels in children.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The correlations between irisin levels, physical activity, and anthropometric measurements have been extensively described in adults with considerable controversy, but little evidence about these relationships has been found in children. The objective of this study is to correlate the plasma levels of irisin in underweight, normal weight, overweight, and obese children with anthropometric parameters and physical activity levels. A cross-sample of 40 children was divided into the following groups on the basis of body mass index (BMI) percentile. The correlations of plasma irisin levels with physical activity, anthropometric, and metabolic measurements were determined. Plasma irisin levels (ng/mL) were lower for the underweight group (164.2 ± 5.95) than for the normal weight and obese groups (182.8 ± 5.58; ). Irisin levels correlated positively with BMI percentile (0.387), waist circumference (0.373), and fat-free mass (0.353; ), but not with body muscle mass (-0.027). After a multiple linear regression analysis, only BMI percentile (0.564; ) showed a positive correlation with irisin. Our results indicated no association with metabolic parameters. A negative correlation with physical activity was observed. Interrelationships among body components might influence irisin levels in children.
AK, Yetisen; N, Jiang; A, Tamayol; GU, Ruiz-Esparza; YS, Zhang; S, Medina-Pando; A, Gupta; JS, Wolffsohn; H, Butt; A, Khademhosseini; SH, Yun
Paper-based microfluidic system for tear electrolyte analysis. Journal Article
In: Lab on a Chip, 2017.
@article{562816,
title = {Paper-based microfluidic system for tear electrolyte analysis.},
author = {Yetisen AK and Jiang N and Tamayol A and Ruiz-Esparza GU and Zhang YS and Medina-Pando S and Gupta A and Wolffsohn JS and Butt H and Khademhosseini A and Yun SH},
url = {http://pubs.rsc.org/en/content/articlelanding/2017/lc/c6lc01450j$#$!divAbstract},
year = {2017},
date = {2017-01-01},
journal = {Lab on a Chip},
abstract = {The analysis of tear constituents at point-of-care settings has a potential for early diagnosis of ocular disorders such as dry eye disease, low-cost screening, and surveillance of at-risk subjects. However, current minimally-invasive rapid tear analysis systems for point-of-care settings have been limited to assessment of osmolarity or inflammatory markers and cannot differentiate between dry eye subclassifications. Here, we demonstrate a portable microfluidic system that allows quantitative analysis of electrolytes in the tear fluid that is suited for point-of-care settings. The microfluidic system consists of a capillary tube for sample collection, a reservoir for sample dilution, and a paper-based microfluidic device for electrolyte analysis. The sensing regions are functionalized with fluorescent crown ethers, o-acetanisidide, and seminaphtorhodafluor that are sensitive to mono- and divalent electrolytes, and their fluorescence outputs are measured with a smartphone readout device. The measured sensitivity values of Na+, K+, Ca2+ ions and pH in artificial tear fluid were matched with the known ion concentrations within the physiological range. The microfluidic system was tested with samples having different ionic concentrations, demonstrating the feasibility for the detection of early-stage dry eye, differential diagnosis of dry eye sub-types, and their severity staging.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The analysis of tear constituents at point-of-care settings has a potential for early diagnosis of ocular disorders such as dry eye disease, low-cost screening, and surveillance of at-risk subjects. However, current minimally-invasive rapid tear analysis systems for point-of-care settings have been limited to assessment of osmolarity or inflammatory markers and cannot differentiate between dry eye subclassifications. Here, we demonstrate a portable microfluidic system that allows quantitative analysis of electrolytes in the tear fluid that is suited for point-of-care settings. The microfluidic system consists of a capillary tube for sample collection, a reservoir for sample dilution, and a paper-based microfluidic device for electrolyte analysis. The sensing regions are functionalized with fluorescent crown ethers, o-acetanisidide, and seminaphtorhodafluor that are sensitive to mono- and divalent electrolytes, and their fluorescence outputs are measured with a smartphone readout device. The measured sensitivity values of Na+, K+, Ca2+ ions and pH in artificial tear fluid were matched with the known ion concentrations within the physiological range. The microfluidic system was tested with samples having different ionic concentrations, demonstrating the feasibility for the detection of early-stage dry eye, differential diagnosis of dry eye sub-types, and their severity staging.
AK, Yetisen; N, Jiang; A, Fallahi; Y, Montelongo; GU, Ruiz-Esparza; A, Tamayol; YS, Zhang; I, Mahmood; SA, Yang; KS, Kim; H, Butt; A, Khademhosseini; SH, Yun
Glucose-Sensitive Hydrogel Optical Fibers Functionalized with Phenylboronic Acid. Journal Article
In: Advanced Materials, 2017.
@article{562811,
title = {Glucose-Sensitive Hydrogel Optical Fibers Functionalized with Phenylboronic Acid.},
author = {Yetisen AK and Jiang N and Fallahi A and Montelongo Y and Ruiz-Esparza GU and Tamayol A and Zhang YS and Mahmood I and Yang SA and Kim KS and Butt H and Khademhosseini A and Yun SH},
url = {http://onlinelibrary.wiley.com/doi/10.1002/adma.201606380/abstract},
year = {2017},
date = {2017-01-01},
journal = {Advanced Materials},
abstract = {Hydrogel optical fibers are utilized for continuous glucose sensing in real time. The hydrogel fibers consist of poly(acrylamide-co-poly(ethylene glycol) diacrylate) cores functionalized with phenylboronic acid. The complexation of the phenylboronic acid and cis-diol groups of glucose enables reversible changes of the hydrogel fiber diameter. The analyses of light propagation loss allow for quantitative glucose measurements within the physiological range.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hydrogel optical fibers are utilized for continuous glucose sensing in real time. The hydrogel fibers consist of poly(acrylamide-co-poly(ethylene glycol) diacrylate) cores functionalized with phenylboronic acid. The complexation of the phenylboronic acid and cis-diol groups of glucose enables reversible changes of the hydrogel fiber diameter. The analyses of light propagation loss allow for quantitative glucose measurements within the physiological range.
K, Brinegar; AK, Yetisen; S, Choi; E, Vallillo; GU, Ruiz-Esparza; AM, Prabhakar; A, Khademhosseini; SH, Yun
The commercialization of genome-editing technologies. Journal Article
In: Critical Reviews in Biotechnology, pp. 1-12, 2017.
@article{562806,
title = {The commercialization of genome-editing technologies.},
author = {Brinegar K and Yetisen AK and Choi S and Vallillo E and Ruiz-Esparza GU and Prabhakar AM and Khademhosseini A and Yun SH},
url = {http://www.tandfonline.com/doi/full/10.1080/07388551.2016.1271768},
year = {2017},
date = {2017-01-01},
journal = {Critical Reviews in Biotechnology},
pages = {1-12},
abstract = {The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance. Although most of the gene-editing technologies originated from the industry, CRISPR has been pioneered by academic research institutions. The spinout of CRISPR biotechnology companies from academic institutions demonstrates a shift in entrepreneurship strategies that were previously led by the industry. These academic institutions, and their subsequent companies, are competing to generate comprehensive intellectual property portfolios to rapidly commercialize CRISPR products. Our analysis shows that the emergence of CRISPR has resulted in a fivefold increase in genome-editing bioenterprise investment over the last year. This entrepreneurial movement has spurred a global biotechnology revolution in the realization of novel gene-editing technologies. This global shift in bioenterprise will continue to grow as the demand for personalized medicine, genetically modified crops and environmentally sustainable biofuels increases. However, the monopolization of intellectual property, negative public perception of genetic engineering and ambiguous regulatory policies may limit the growth of these market segments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance. Although most of the gene-editing technologies originated from the industry, CRISPR has been pioneered by academic research institutions. The spinout of CRISPR biotechnology companies from academic institutions demonstrates a shift in entrepreneurship strategies that were previously led by the industry. These academic institutions, and their subsequent companies, are competing to generate comprehensive intellectual property portfolios to rapidly commercialize CRISPR products. Our analysis shows that the emergence of CRISPR has resulted in a fivefold increase in genome-editing bioenterprise investment over the last year. This entrepreneurial movement has spurred a global biotechnology revolution in the realization of novel gene-editing technologies. This global shift in bioenterprise will continue to grow as the demand for personalized medicine, genetically modified crops and environmentally sustainable biofuels increases. However, the monopolization of intellectual property, negative public perception of genetic engineering and ambiguous regulatory policies may limit the growth of these market segments.
Annabi, N; Zhang, Y.; Assmann, A; Sani, E Shirzaei; Vegh, A; Cheng, G.; Dehghani, B; Ruiz-Esparza, GU; Wang, X.; Lassaletta, AS; Gangadharan, S; Weiss, AS; A, Khademhosseini
Development of an Elastic and Adhesive Sealant for Surgical Applications Conference
Tissue Engineering Part A, vol. 23, 2017.
@conference{595711,
title = {Development of an Elastic and Adhesive Sealant for Surgical Applications},
author = {N Annabi and Y. Zhang and A Assmann and E Shirzaei Sani and A Vegh and G. Cheng and B Dehghani and GU Ruiz-Esparza and X. Wang and AS Lassaletta and S Gangadharan and AS Weiss and Khademhosseini A},
url = {http://online.liebertpub.com/doi/pdf/10.1089/ten.tea.2017.29003.abstracts},
year = {2017},
date = {2017-01-01},
booktitle = {Tissue Engineering Part A},
volume = {23},
pages = {S123-S123},
abstract = {Conventional surgical sealants have been used for sealing or repairing defects often suffer from low adhesion strength, insufficient mechanical stability and strength, cytotoxic degradation products, and weak performance in biological environments. Therefore, in this study we aimed to engineer a photocrosslinked and highly biocompatible sealant with tunable mechanical and adhesion properties using tropoelastin, as a genetically modified human protein. We tuned the degree of methacrylation of tropoelastin and prepolymer concentration to optimize the physical properties and adhesion strength of the methacryloyl-substituted tropoelastin (MeTro) hydrogel for sealing of elastic and soft tissues. Following ASTM standard tests, the MeTro hydrogels revealed superior adhesive strength and burst pressure values compared to the commercially available sealants. The subcutaneous implantation of the engineered MeTro hydrogels in rats exhibited minimal inflammatory host responses and slow biodegradation of sealant. The in vivo and ex vivo burst pressure resistance of bioengineered MeTro sealants was tested on lungs and arteries in small as well as translational large animal models. Our results proved MeTro sealant to effectively seal lung and artery leakages without the need for sutures or staples, presenting a significant improvement compared to the commercially available clinical sealants (Evicel and ProgelTM) and sutures only. Combining these results, we envision that the engineered MeTro sealant has the potential to be commercialized due to its remarkable mechanicalstrength, biocompatibility, biodegradability and strong adhesive interaction between the sealant and the wound tissue without the need for suturing.},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
Conventional surgical sealants have been used for sealing or repairing defects often suffer from low adhesion strength, insufficient mechanical stability and strength, cytotoxic degradation products, and weak performance in biological environments. Therefore, in this study we aimed to engineer a photocrosslinked and highly biocompatible sealant with tunable mechanical and adhesion properties using tropoelastin, as a genetically modified human protein. We tuned the degree of methacrylation of tropoelastin and prepolymer concentration to optimize the physical properties and adhesion strength of the methacryloyl-substituted tropoelastin (MeTro) hydrogel for sealing of elastic and soft tissues. Following ASTM standard tests, the MeTro hydrogels revealed superior adhesive strength and burst pressure values compared to the commercially available sealants. The subcutaneous implantation of the engineered MeTro hydrogels in rats exhibited minimal inflammatory host responses and slow biodegradation of sealant. The in vivo and ex vivo burst pressure resistance of bioengineered MeTro sealants was tested on lungs and arteries in small as well as translational large animal models. Our results proved MeTro sealant to effectively seal lung and artery leakages without the need for sutures or staples, presenting a significant improvement compared to the commercially available clinical sealants (Evicel and ProgelTM) and sutures only. Combining these results, we envision that the engineered MeTro sealant has the potential to be commercialized due to its remarkable mechanicalstrength, biocompatibility, biodegradability and strong adhesive interaction between the sealant and the wound tissue without the need for suturing.
2016
GU, Ruiz-Esparza; V, Segura-Ibarra; AM, Cordero-Reyes; KA, Youker; RE, Serda; AS, Cruz-Solbes; J, Amione-Guerra; K, Yokoi; DK, Kirui; FE, Cara; J, Paez-Mayorga; JH, Flores-Arredondo; CE, Guerrero-Beltran; G, Garcia-Rivas; M, Ferrari; E, Blanco; G, Torre-Amione
In: European Journal of Heart Failure, vol. 18, no. 2, pp. 169-78, 2016.
@article{562791,
title = {A specifically designed nanoconstruct associates, internalizes, traffics in cardiovascular cells, and accumulates in failing myocardium: a new strategy for heart failure diagnostics and therapeutics.},
author = {Ruiz-Esparza GU and Segura-Ibarra V and Cordero-Reyes AM and Youker KA and Serda RE and Cruz-Solbes AS and Amione-Guerra J and Yokoi K and Kirui DK and Cara FE and Paez-Mayorga J and Flores-Arredondo JH and Guerrero-Beltran CE and Garcia-Rivas G and Ferrari M and Blanco E and Torre-Amione G},
url = {http://onlinelibrary.wiley.com/doi/10.1002/ejhf.463/full},
year = {2016},
date = {2016-01-01},
journal = {European Journal of Heart Failure},
volume = {18},
number = {2},
pages = {169-78},
abstract = {Aims
Ongoing inflammation and endothelial dysfunction occurs within the local microenvironment of heart failure, creating an appropriate scenario for successful use and delivery of nanovectors. This study sought to investigate whether cardiovascular cells associate, internalize, and traffic a nanoplatform called mesoporous silicon vector (MSV), and determine its intravenous accumulation in cardiac tissue in a murine model of heart failure.
Methods and results
In vitro cellular uptake and intracellular trafficking of MSVs was examined by scanning electron microscopy, confocal microscopy, time-lapse microscopy, and flow cytometry in cardiac myocytes, fibroblasts, smooth muscle cells, and endothelial cells. The MSVs were internalized within the first hours, and trafficked to perinuclear regions in all the cell lines. Cytotoxicity was investigated by annexin V and cell cycle assays. No significant evidence of toxicity was found. In vivo intravenous cardiac accumulation of MSVs was examined by high content fluorescence and confocal microscopy, with results showing increased accumulation of particles in failing hearts compared with normal hearts. Similar to observations in vitro, MSVs were able to associate, internalize, and traffic to the perinuclear region of cardiomyocytes in vivo.
Conclusions
Results show that MSVs associate, internalize, and traffic in cardiovascular cells without any significant toxicity. Furthermore, MSVs accumulate in failing myocardium after intravenous administration, reaching intracellular regions of the cardiomyocytes. These findings represent a novel avenue to develop nanotechnology-based therapeutics and diagnostics in heart failure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aims
Ongoing inflammation and endothelial dysfunction occurs within the local microenvironment of heart failure, creating an appropriate scenario for successful use and delivery of nanovectors. This study sought to investigate whether cardiovascular cells associate, internalize, and traffic a nanoplatform called mesoporous silicon vector (MSV), and determine its intravenous accumulation in cardiac tissue in a murine model of heart failure.
Methods and results
In vitro cellular uptake and intracellular trafficking of MSVs was examined by scanning electron microscopy, confocal microscopy, time-lapse microscopy, and flow cytometry in cardiac myocytes, fibroblasts, smooth muscle cells, and endothelial cells. The MSVs were internalized within the first hours, and trafficked to perinuclear regions in all the cell lines. Cytotoxicity was investigated by annexin V and cell cycle assays. No significant evidence of toxicity was found. In vivo intravenous cardiac accumulation of MSVs was examined by high content fluorescence and confocal microscopy, with results showing increased accumulation of particles in failing hearts compared with normal hearts. Similar to observations in vitro, MSVs were able to associate, internalize, and traffic to the perinuclear region of cardiomyocytes in vivo.
Conclusions
Results show that MSVs associate, internalize, and traffic in cardiovascular cells without any significant toxicity. Furthermore, MSVs accumulate in failing myocardium after intravenous administration, reaching intracellular regions of the cardiomyocytes. These findings represent a novel avenue to develop nanotechnology-based therapeutics and diagnostics in heart failure.
Ongoing inflammation and endothelial dysfunction occurs within the local microenvironment of heart failure, creating an appropriate scenario for successful use and delivery of nanovectors. This study sought to investigate whether cardiovascular cells associate, internalize, and traffic a nanoplatform called mesoporous silicon vector (MSV), and determine its intravenous accumulation in cardiac tissue in a murine model of heart failure.
Methods and results
In vitro cellular uptake and intracellular trafficking of MSVs was examined by scanning electron microscopy, confocal microscopy, time-lapse microscopy, and flow cytometry in cardiac myocytes, fibroblasts, smooth muscle cells, and endothelial cells. The MSVs were internalized within the first hours, and trafficked to perinuclear regions in all the cell lines. Cytotoxicity was investigated by annexin V and cell cycle assays. No significant evidence of toxicity was found. In vivo intravenous cardiac accumulation of MSVs was examined by high content fluorescence and confocal microscopy, with results showing increased accumulation of particles in failing hearts compared with normal hearts. Similar to observations in vitro, MSVs were able to associate, internalize, and traffic to the perinuclear region of cardiomyocytes in vivo.
Conclusions
Results show that MSVs associate, internalize, and traffic in cardiovascular cells without any significant toxicity. Furthermore, MSVs accumulate in failing myocardium after intravenous administration, reaching intracellular regions of the cardiomyocytes. These findings represent a novel avenue to develop nanotechnology-based therapeutics and diagnostics in heart failure.
2015
GU, Ruiz Esparza; A, Cordero-Reyes; Youker, KA; M, Ferrari; E, Blanco; G, Torre-Amione
European Society of Cardiology, Seville, Spain, 2015.
@proceedings{562876,
title = {Nanotechnology-based delivery system for the transport of therapeutic and diagnostic molecules to the failing heart.},
author = {Ruiz Esparza GU and Cordero-Reyes A and KA Youker and Ferrari M and Blanco E and Torre-Amione G},
url = {http://spo.escardio.org/SessionDetails.aspx?eevtid=1077&sessId=16359$#$.Wbtpe7pFygk},
year = {2015},
date = {2015-01-01},
journal = {Heart Failure 2015 / World Congress on Acute Heart Failure},
publisher = {European Society of Cardiology},
address = {Seville, Spain},
abstract = {Background: Treatment of heart failure has been limited by the inability to deliver high drug concentrations within the myocardium without significant systemic side effects and by the lack of efficient non-invasive methods for gene delivery into the myocardium. Nanotechnology platforms represent a potential strategy to transport drugs and genes in heart failure. We hypothesized that the changes present in the failing myocardium, result in increased vascular permeability due to endothelial dysfunction, allowing migration of intravenously administered silicon nanoconstructs from the vasculature to within the myocardium. Methods: Male C57BL/6 mice with normal and failing hearts were administered intravenously with silicon nanoconstructs (109, 0.2 mg). After 24 h, mice were sacrificed and heart tissues were extracted and sectioned. To examine accumulation and homogeneity of the nanoconstructs in different cardiac regions, sections of normal and failing hearts were captured using wield field high content fluorescence imaging system. Cellular and sub-cellular localization of nanoconstructs was evaluated via immunofluorescence using confocal microscopy and z-stacking. Area fraction analysis and particle number was determined and quantified analyzing the fluorescence emitted by the nanoconstructs and the tissue. Results: Passive intra-cardiac accumulation of high concentrations of nanocarriers occurred after a single application during the course of 24 h. Image analysis of the cardiac tissue showed intracellular uptake and transport of the nanoconstructs to the perinuclear region of cardiomyoctes. Control hearts showed slight green fluorescence associated with the nanoconstructs, whereas failing heart sections were highly enriched with fluorescence within different regions, indicating a 14-fold increase in accumulation of nanoconstructs. The highest levels of accumulation and co-localization of the nanoconstructs were present in cardiomyocytes. Conclusions: In summary, silicon nanoconstructs successfully accumulated in higher amounts in failing hearts compared to normal hearts, reaching the perinuclear region of the cardiomyocytes. The use of nanotechnology in heart failure, has the potential to achieve cardiac delivery of several moieties such as hydrophobic drugs, proteins, genetic material, or imaging and diagnostic agents in a safe, non-invasive, stable and protected fashion without degradation.},
keywords = {},
pubstate = {published},
tppubtype = {proceedings}
}
Background: Treatment of heart failure has been limited by the inability to deliver high drug concentrations within the myocardium without significant systemic side effects and by the lack of efficient non-invasive methods for gene delivery into the myocardium. Nanotechnology platforms represent a potential strategy to transport drugs and genes in heart failure. We hypothesized that the changes present in the failing myocardium, result in increased vascular permeability due to endothelial dysfunction, allowing migration of intravenously administered silicon nanoconstructs from the vasculature to within the myocardium. Methods: Male C57BL/6 mice with normal and failing hearts were administered intravenously with silicon nanoconstructs (109, 0.2 mg). After 24 h, mice were sacrificed and heart tissues were extracted and sectioned. To examine accumulation and homogeneity of the nanoconstructs in different cardiac regions, sections of normal and failing hearts were captured using wield field high content fluorescence imaging system. Cellular and sub-cellular localization of nanoconstructs was evaluated via immunofluorescence using confocal microscopy and z-stacking. Area fraction analysis and particle number was determined and quantified analyzing the fluorescence emitted by the nanoconstructs and the tissue. Results: Passive intra-cardiac accumulation of high concentrations of nanocarriers occurred after a single application during the course of 24 h. Image analysis of the cardiac tissue showed intracellular uptake and transport of the nanoconstructs to the perinuclear region of cardiomyoctes. Control hearts showed slight green fluorescence associated with the nanoconstructs, whereas failing heart sections were highly enriched with fluorescence within different regions, indicating a 14-fold increase in accumulation of nanoconstructs. The highest levels of accumulation and co-localization of the nanoconstructs were present in cardiomyocytes. Conclusions: In summary, silicon nanoconstructs successfully accumulated in higher amounts in failing hearts compared to normal hearts, reaching the perinuclear region of the cardiomyocytes. The use of nanotechnology in heart failure, has the potential to achieve cardiac delivery of several moieties such as hydrophobic drugs, proteins, genetic material, or imaging and diagnostic agents in a safe, non-invasive, stable and protected fashion without degradation.
2014
GU, Ruiz-Esparza; S, Wu; V, Segura-Ibarra; FE, Cara; KW, Evans; M, Milosevic; A, Ziemys; M, Kojic; F, Meric-Bernstam; M, Ferrari; E, Blanco
Polymer Nanoparticles Encased in a Cyclodextrin Complex Shell for Potential Site- and Sequence-Specific Drug Release. Journal Article
In: Advanced Functional Materials, vol. 24, no. 30, pp. 4753-61, 2014.
@article{562796,
title = {Polymer Nanoparticles Encased in a Cyclodextrin Complex Shell for Potential Site- and Sequence-Specific Drug Release.},
author = {Ruiz-Esparza GU and Wu S and Segura-Ibarra V and Cara FE and Evans KW and Milosevic M and Ziemys A and Kojic M and Meric-Bernstam F and Ferrari M and Blanco E},
url = {http://onlinelibrary.wiley.com/doi/10.1002/adfm.201400011/abstract},
year = {2014},
date = {2014-01-01},
journal = {Advanced Functional Materials},
volume = {24},
number = {30},
pages = {4753-61},
abstract = {Time-staggered combination chemotherapy strategies show immense potential in cell culture systems, but fail to successfully translate clinically due to different routes of administration and disparate formulation parameters that preclude a specific order of drug presentation. A novel platform consisting of drug-containing PLGA polymer nanoparticles, stably fashioned with a shell composed of drug complexed with cationic cyclodextrin, capable of releasing drugs time- and sequence-specifically within tumors is designed. Morphological examination of nanoparticles measuring 150 nm highlight stable and distinct compartmentalization of model drugs, rhodamine and bodipy, within the core and shell, respectively. Sequential release is observed in vitro, owing to cyclodextrin shell displacement and subsequent sustained release of core-loaded drug, kinetics preserved in breast cancer cells following internalization. Importantly, time-staggered release is corroborated in a murine breast cancer model following intravenous administration. Precise control of drug release order, site-specifically, potentially opens novel avenues in polychemotherapy for synergy and chemosensitization strategies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Time-staggered combination chemotherapy strategies show immense potential in cell culture systems, but fail to successfully translate clinically due to different routes of administration and disparate formulation parameters that preclude a specific order of drug presentation. A novel platform consisting of drug-containing PLGA polymer nanoparticles, stably fashioned with a shell composed of drug complexed with cationic cyclodextrin, capable of releasing drugs time- and sequence-specifically within tumors is designed. Morphological examination of nanoparticles measuring 150 nm highlight stable and distinct compartmentalization of model drugs, rhodamine and bodipy, within the core and shell, respectively. Sequential release is observed in vitro, owing to cyclodextrin shell displacement and subsequent sustained release of core-loaded drug, kinetics preserved in breast cancer cells following internalization. Importantly, time-staggered release is corroborated in a murine breast cancer model following intravenous administration. Precise control of drug release order, site-specifically, potentially opens novel avenues in polychemotherapy for synergy and chemosensitization strategies.
E, Blanco; T, Sangai; S, Wu; A, Hsiao; GU, Ruiz-Esparza; CA, Gonzalez-Delgado; FE, Cara; S, Granados-Principal; KW, Evans; A, Akcakanat; Y, Wang; KA, Do; F, Meric-Bernstam; M, Ferrari
Colocalized Delivery of Rapamycin and Paclitaxel to Tumors Enhances Synergistic Targeting of the PI3K/Akt/mTOR Pathway Journal Article
In: Molecular Therapy, vol. 22, no. 7, pp. 1310-9, 2014.
@article{562801,
title = {Colocalized Delivery of Rapamycin and Paclitaxel to Tumors Enhances Synergistic Targeting of the PI3K/Akt/mTOR Pathway},
author = {Blanco E and Sangai T and Wu S and Hsiao A and Ruiz-Esparza GU and Gonzalez-Delgado CA and Cara FE and Granados-Principal S and Evans KW and Akcakanat A and Wang Y and Do KA and Meric-Bernstam F and Ferrari M},
url = {http://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(16)30722-5},
year = {2014},
date = {2014-01-01},
journal = {Molecular Therapy},
volume = {22},
number = {7},
pages = {1310-9},
abstract = {Ongoing clinical trials target the aberrant PI3K/Akt/mammalian target of rapamycin (mTOR) pathway in breast cancer through administration of rapamycin, an allosteric mTOR inhibitor, in combination with paclitaxel. However, synergy may not be fully exploited clinically because of distinct pharmacokinetic parameters of drugs. This study explores the synergistic potential of site-specific, colocalized delivery of rapamycin and paclitaxel through nanoparticle incorporation. Nanoparticle drug loading was accurately controlled, and synergistic drug ratios established in vitro. Precise drug ratios were maintained in tumors 48 hours after nanoparticle administration to mice, at levels twofold greater than liver and spleen, yielding superior antitumor activity compared to controls. Simultaneous and preferential in vivo delivery of rapamycin and paclitaxel to tumors yielded mechanistic insights into synergy involving suppression of feedback loop Akt phosphorylation and its downstream targets. Findings demonstrate that a same time, same place, and specific amount approach to combination chemotherapy by means of nanoparticle delivery has the potential to successfully translate in vitro synergistic findings in vivo. Predictive in vitro models can be used to determine optimum drug ratios for antitumor efficacy, while nanoparticle delivery of combination chemotherapies in preclinical animal models may lead to enhanced understanding of mechanisms of synergy, ultimately opening several avenues for personalized therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ongoing clinical trials target the aberrant PI3K/Akt/mammalian target of rapamycin (mTOR) pathway in breast cancer through administration of rapamycin, an allosteric mTOR inhibitor, in combination with paclitaxel. However, synergy may not be fully exploited clinically because of distinct pharmacokinetic parameters of drugs. This study explores the synergistic potential of site-specific, colocalized delivery of rapamycin and paclitaxel through nanoparticle incorporation. Nanoparticle drug loading was accurately controlled, and synergistic drug ratios established in vitro. Precise drug ratios were maintained in tumors 48 hours after nanoparticle administration to mice, at levels twofold greater than liver and spleen, yielding superior antitumor activity compared to controls. Simultaneous and preferential in vivo delivery of rapamycin and paclitaxel to tumors yielded mechanistic insights into synergy involving suppression of feedback loop Akt phosphorylation and its downstream targets. Findings demonstrate that a same time, same place, and specific amount approach to combination chemotherapy by means of nanoparticle delivery has the potential to successfully translate in vitro synergistic findings in vivo. Predictive in vitro models can be used to determine optimum drug ratios for antitumor efficacy, while nanoparticle delivery of combination chemotherapies in preclinical animal models may lead to enhanced understanding of mechanisms of synergy, ultimately opening several avenues for personalized therapy.
2013
GU, Ruiz-Esparza; E, Blanco; S, Shamsdueen; JH, Flores-Arredondo; R, Serda; M, Ferrari; G, Torre-Amione
Cellular association of nanocarriers in cardiac cells. Conference
Journal of the American College of Cardiology, vol. 61, ACC.13 – American College of Cardiology 62nd Annual Scientific Session & Expo ACC.13 – American College of Cardiology 62nd Annual Scientific Session & Expo, San Francisco, California, USA, 2013.
@conference{562861,
title = {Cellular association of nanocarriers in cardiac cells.},
author = {Ruiz-Esparza GU and Blanco E and Shamsdueen S and Flores-Arredondo JH and Serda R and Ferrari M and Torre-Amione G},
url = {https://www.infona.pl/resource/bwmeta1.element.elsevier-4c4a42da-09b1-3019-8e82-e8d0094824c5/tab/summary},
year = {2013},
date = {2013-01-01},
booktitle = {Journal of the American College of Cardiology},
volume = {61},
pages = {E1834},
publisher = {ACC.13 – American College of Cardiology 62nd Annual Scientific Session & Expo},
address = {San Francisco, California, USA},
edition = {10},
organization = {ACC.13 – American College of Cardiology 62nd Annual Scientific Session & Expo},
abstract = {Background: Mesoporous silicon particles (MSVs) offer delivery of nanotherapeutics in a sustained fashion, while biofunctionalization with targeting ligands enhances accumulation in target tissues. We hypothesize MSVs can be internalized by cardiac cells, after which they can deliver powerful payloads of therapeutics including siRNA and genes. Intracellular uptake of MSVs was investigated in cardiac myocytes (CM), cardiac fibroblasts (CF), cardiac smooth muscle cells (CSMC) and cardiac endothelial cells (CEC).Methods: Negatively charged fluorescent nanoparticles (10nm) were loaded within pores of positively charged MSVs (1μmx400nm). In vitro uptake in a ratio of 25 MSVs per cell was evaluated after 3 hours of incubation via image stream analysis, as well as confocal and scanning electron microscopy.Results: MSVs underwent cellular uptake, resulting in intracellular trafficking. Data obtained by image stream analysis allowed for quantification of MSV uptake rate as a function of cell area. The mean uptake count per cell was 18, 16 and 4 for CEC, CSMC and CF respectively. CM were subjectively quantified via microscopy resulting in a 25% enhancement of MSV capture compared with CSMC.Conclusions: Cardiac cells can effectively internalize MSVs, with differences arising from cellular morphology and intracellular trafficking. Multifunctional delivery systems, molecularly targeted with high affinity ligands, could have vast potential in personalized delivery of therapeutics to cardiac cells.},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
Background: Mesoporous silicon particles (MSVs) offer delivery of nanotherapeutics in a sustained fashion, while biofunctionalization with targeting ligands enhances accumulation in target tissues. We hypothesize MSVs can be internalized by cardiac cells, after which they can deliver powerful payloads of therapeutics including siRNA and genes. Intracellular uptake of MSVs was investigated in cardiac myocytes (CM), cardiac fibroblasts (CF), cardiac smooth muscle cells (CSMC) and cardiac endothelial cells (CEC).Methods: Negatively charged fluorescent nanoparticles (10nm) were loaded within pores of positively charged MSVs (1μmx400nm). In vitro uptake in a ratio of 25 MSVs per cell was evaluated after 3 hours of incubation via image stream analysis, as well as confocal and scanning electron microscopy.Results: MSVs underwent cellular uptake, resulting in intracellular trafficking. Data obtained by image stream analysis allowed for quantification of MSV uptake rate as a function of cell area. The mean uptake count per cell was 18, 16 and 4 for CEC, CSMC and CF respectively. CM were subjectively quantified via microscopy resulting in a 25% enhancement of MSV capture compared with CSMC.Conclusions: Cardiac cells can effectively internalize MSVs, with differences arising from cellular morphology and intracellular trafficking. Multifunctional delivery systems, molecularly targeted with high affinity ligands, could have vast potential in personalized delivery of therapeutics to cardiac cells.
GU, Ruiz-Esparza; JH, Flores-Arredondo; V, Segura-Ibarra; G, Torre-Amione; M, Ferrari; E, Blanco; RE, Serda
The physiology of cardiovascular disease and innovative liposomal platforms for therapy. Journal Article
In: International Journal of Nanomedicine., vol. 8, pp. 629-40, 2013.
@article{562756,
title = {The physiology of cardiovascular disease and innovative liposomal platforms for therapy.},
author = {Ruiz-Esparza GU and Flores-Arredondo JH and Segura-Ibarra V and Torre-Amione G and Ferrari M and Blanco E and Serda RE},
url = {https://www.dovepress.com/the-physiology-of-cardiovascular-disease-and-innovative-liposomal-plat-peer-reviewed-article-IJN},
year = {2013},
date = {2013-01-01},
journal = {International Journal of Nanomedicine.},
volume = {8},
pages = {629-40},
abstract = {Heart disease remains the major cause of death in males and females, emphasizing the need for novel strategies to improve patient treatment and survival. A therapeutic approach, still in its infancy, is the development of site-specific drug-delivery systems. Nanoparticle-based delivery systems, such as liposomes, have evolved into robust platforms for site-specific delivery of therapeutics. In this review, the clinical impact of cardiovascular disease and the pathophysiology of different subsets of the disease are described. Potential pathological targets for therapy are introduced, and promising advances in nanotherapeutic cardiovascular applications involving liposomal platforms are presented.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Heart disease remains the major cause of death in males and females, emphasizing the need for novel strategies to improve patient treatment and survival. A therapeutic approach, still in its infancy, is the development of site-specific drug-delivery systems. Nanoparticle-based delivery systems, such as liposomes, have evolved into robust platforms for site-specific delivery of therapeutics. In this review, the clinical impact of cardiovascular disease and the pathophysiology of different subsets of the disease are described. Potential pathological targets for therapy are introduced, and promising advances in nanotherapeutic cardiovascular applications involving liposomal platforms are presented.
2012
E, Blanco; S, Takafumi; A, Hsiao; GU, Ruiz-Esparza; M, Ferrari; F, Meric-Bernstam
Cancer Research, vol. 72, Thirty-Fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium Thirty-Fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, 2012.
@conference{562856,
title = {Site-Specific, Concomitant Delivery of Rapamycin and Paclitaxel in Breast Cancer: Consequent Synergistic Efficacy Enhancement},
author = {Blanco E and Takafumi S and Hsiao A and Ruiz-Esparza GU and Ferrari M and Meric-Bernstam F},
url = {http://cancerres.aacrjournals.org/content/72/24_Supplement/P6-11-03},
year = {2012},
date = {2012-01-01},
booktitle = {Cancer Research},
volume = {72},
pages = {P6-11-03-P6-11-03},
publisher = {Thirty-Fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium},
address = {San Antonio, Texas, USA},
edition = {24 Supplement},
organization = {Thirty-Fifth Annual CTRC-AACR San Antonio Breast Cancer Symposium},
abstract = {
Background: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) (PI3k/Akt/mTOR) pathway is dysregulated in certain breast cancers. Ongoing clinical trials aim to therapeutically exploit this pathway through administration of rapamycin (RAP), an mTOR inhibitor, in combination with paclitaxel (PTX). However, actual drug synergy in clinical settings may not be fully realized due to disparate pharmacokinetic parameters of individual drug formulations, wherein drugs or their effects may never be present in the tumor at the same time. Our objective was to generate a nanoparticle platform capable of site-specifically delivering precise amounts of rapamycin and paclitaxel to breast tumors with hopes of increasing synergistic targeting of the PI3k/Akt/mTOR pathway. Materials and Methods: Drug-containing nanoparticles composed of amphiphilic block copolymers of pegylated poly(∈-caprolactone) (PEG-PCL},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
Background: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) (PI3k/Akt/mTOR) pathway is dysregulated in certain breast cancers. Ongoing clinical trials aim to therapeutically exploit this pathway through administration of rapamycin (RAP), an mTOR inhibitor, in combination with paclitaxel (PTX). However, actual drug synergy in clinical settings may not be fully realized due to disparate pharmacokinetic parameters of individual drug formulations, wherein drugs or their effects may never be present in the tumor at the same time. Our objective was to generate a nanoparticle platform capable of site-specifically delivering precise amounts of rapamycin and paclitaxel to breast tumors with hopes of increasing synergistic targeting of the PI3k/Akt/mTOR pathway. Materials and Methods: Drug-containing nanoparticles composed of amphiphilic block copolymers of pegylated poly(∈-caprolactone) (PEG-PCL
2011
CH, Loo; IM, Meraz; HA, Anderson; G, Qin; J, DeLaCerda; GU, Ruiz-Esparza; V, Rubio-Calva; LA, Diaz; KC, Li; RE, Serda
Mesoporous Silicon-Based Antigen Delivery Constructs for Cancer Vaccine Prevention and Therapy. Conference
BMES Annual Meeting 2011, Biomedical Engineering Society Biomedical Engineering Society, Hartford, Connecticut, USA, 2011.
@conference{562866,
title = {Mesoporous Silicon-Based Antigen Delivery Constructs for Cancer Vaccine Prevention and Therapy.},
author = {Loo CH and Meraz IM and Anderson HA and Qin G and DeLaCerda J and Ruiz-Esparza GU and Rubio-Calva V and Diaz LA and Li KC and Serda RE},
year = {2011},
date = {2011-01-01},
booktitle = {BMES Annual Meeting 2011},
publisher = {Biomedical Engineering Society},
address = {Hartford, Connecticut, USA},
organization = {Biomedical Engineering Society},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
E, Blanco; A, Hsiao; GU, Ruiz-Esparza; MG, Landry; F, Meric-Bernstam; M, Ferrari
Molecular-targeted nanotherapies in cancer: enabling treatment specificity. Journal Article
In: Molecular Oncology, vol. 5, no. 6, pp. 492-503, 2011.
@article{562751,
title = {Molecular-targeted nanotherapies in cancer: enabling treatment specificity.},
author = {Blanco E and Hsiao A and Ruiz-Esparza GU and Landry MG and Meric-Bernstam F and Ferrari M},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528328/},
year = {2011},
date = {2011-01-01},
journal = {Molecular Oncology},
volume = {5},
number = {6},
pages = {492-503},
abstract = {Chemotherapy represents a mainstay and powerful adjuvant therapy in the treatment of cancer. The field has evolved from drugs possessing all-encompassing cell-killing effects to those with highly targeted, specific mechanisms of action; a direct byproduct of enhanced understanding of tumorigenic processes. However, advances regarding development of agents that target key molecules and dysregulated pathways have had only modest impacts on patient survival. Several biological barriers preclude adequate delivery of drugs to tumors, and remain a formidable challenge to overcome in chemotherapy. Currently, the field of nanomedicine is enabling the delivery of chemotherapeutics, including repositioned drugs and siRNAs, by giving rise to carriers that provide for protection from degradation, prolonged circulation times, and increased tumor accumulation, all the while resulting in reduced patient morbidity. This review aims to highlight several innovative, nanoparticle-based platforms with the potential of providing clinical translation of several novel chemotherapeutic agents. We will also summarize work regarding the development of a multistage drug delivery strategy, a robust carrier platform designed to overcome several biological barriers while en route to tumors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chemotherapy represents a mainstay and powerful adjuvant therapy in the treatment of cancer. The field has evolved from drugs possessing all-encompassing cell-killing effects to those with highly targeted, specific mechanisms of action; a direct byproduct of enhanced understanding of tumorigenic processes. However, advances regarding development of agents that target key molecules and dysregulated pathways have had only modest impacts on patient survival. Several biological barriers preclude adequate delivery of drugs to tumors, and remain a formidable challenge to overcome in chemotherapy. Currently, the field of nanomedicine is enabling the delivery of chemotherapeutics, including repositioned drugs and siRNAs, by giving rise to carriers that provide for protection from degradation, prolonged circulation times, and increased tumor accumulation, all the while resulting in reduced patient morbidity. This review aims to highlight several innovative, nanoparticle-based platforms with the potential of providing clinical translation of several novel chemotherapeutic agents. We will also summarize work regarding the development of a multistage drug delivery strategy, a robust carrier platform designed to overcome several biological barriers while en route to tumors.