@article{714a828a683f48cdb5d84f1b5bb902aa,
title = "Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation",
abstract = "Cell encapsulation is an attractive transplantation strategy to treat endocrine disorders. Transplanted cells offer a dynamic and stimulus-responsive system that secretes therapeutics based on patient need. Despite significant advancements, a challenge in allogeneic cell encapsulation is maintaining sufficient oxygen and nutrient exchange, while providing protection from the host immune system. To this end, we developed a subcutaneously implantable dual-reservoir encapsulation system integrating in situ prevascularization and local immunosuppressant delivery, termed NICHE. NICHE structure is 3D-printed in biocompatible polyamide 2200 and comprises of independent cell and drug reservoirs separated by a nanoporous membrane for sustained local release of immunosuppressant. Here we present the development and characterization of NICHE, as well as efficacy validation for allogeneic cell transplantation in an immunocompetent rat model. We established biocompatibility and mechanical stability of NICHE. Further, NICHE vascularization was achieved with the aid of mesenchymal stem cells. Our study demonstrated sustained local elution of immunosuppressant (CTLA4Ig) into the cell reservoir protected transcutaneously-transplanted allogeneic Leydig cells from host immune destruction during a 31-day study, and reduced systemic drug exposure by 12-fold. In summary, NICHE is the first encapsulation platform achieving both in situ vascularization and immunosuppressant delivery, presenting a viable strategy for allogeneic cell transplantation.",
keywords = "CTLA4Ig, Leydig cells, Local immunosuppression, Subcutaneous implant, Vascularization",
author = "Jesus Paez-Mayorga and Simone Capuani and Nathanael Hernandez and Marco Farina and Chua, {Corrine Ying Xuan} and Ryan Blanchard and Antons Sizovs and Liu, {Hsuan Chen} and Fraga, {Daniel W.} and Niles, {Jean A.} and Salazar, {Hector F.} and Bruna Corradetti and Sikora, {Andrew G.} and Malgorzata Kloc and Li, {Xian C.} and Gaber, {A. Osama} and Nichols, {Joan E.} and Alessandro Grattoni",
note = "Funding Information: Funding support was received from the Juvenile Diabetes Research Foundation (1-INO-2018-595-A) (A.G.), the Vivian L. Smith Foundation (A.G.), and the Houston Methodist Research Institute (A.G.). Additional support was received from Frank J. and Jean Raymond Centennial Chair Endowment (A.G.). J.P. received funding support from Tecnologico de Monterrey and Consejo Nacional de Ciencia y Tecnologia. We thank Dr. Jianhua (James) Gu from the electron microscopy core of Houston Methodist Research Institute, Dr. Andreana L. Rivera, Yuelan Ren, and Sandra Steptoe from the research pathology core of Houston Methodist Research Institute, and Jack Ratliff of Ratliff Histology for processing of samples. We also thank Fernanda Paola Pons-Faudoa and Dixita Viswanath for their assistance in implantation surgeries. Funding Information: Funding support was received from the Juvenile Diabetes Research Foundation (1-INO-2018-595-A) (A.G.), the Vivian L. Smith Foundation (A.G.), and the Houston Methodist Research Institute (A.G.). Additional support was received from Frank J. and Jean Raymond Centennial Chair Endowment (A.G.). J.P. received funding support from Tecnologico de Monterrey and Consejo Nacional de Ciencia y Tecnologia. We thank Dr. Jianhua (James) Gu from the electron microscopy core of Houston Methodist Research Institute, Dr. Andreana L. Rivera, Yuelan Ren, and Sandra Steptoe from the research pathology core of Houston Methodist Research Institute, and Jack Ratliff of Ratliff Histology for processing of samples. We also thank Fernanda Paola Pons-Faudoa and Dixita Viswanath for their assistance in implantation surgeries. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = oct,
doi = "10.1016/j.biomaterials.2020.120232",
language = "English (US)",
volume = "257",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
}