Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation

Jesus Paez-Mayorga, Simone Capuani, Nathanael Hernandez, Marco Farina, Ying Xuan Chua, Ryan Blanchard, Antons Sizovs, Hsuan Chen Liu, Daniel W. Fraga, Jean A. Niles, Hector F. Salazar, Bruna Corradetti, Andrew G. Sikora, Malgorzata Kloc, Xian C. Li, A. Osama Gaber, Joan Nichols, Alessandro Grattoni

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Article number120232
JournalBiomaterials
Volume257
DOIs
StatePublished - Oct 2020

Keywords

  • CTLA4Ig
  • Leydig cells
  • Local immunosuppression
  • Subcutaneous implant
  • Vascularization

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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