Immunosuppression-free electrospun macroencapsulation devices with immunoprotective features for cell transplantation therapies.

Immunoisolated cell transplantation offers a promising strategy for multiple endocrine insufficiencies by restoring physiological hormone secretion without systemic immunosuppression. It employs semi-permeable biomaterial encapsulation to permit the exchange of nutrients, oxygen, hormones, and growth factors, while preventing immune-mediated graft rejection. We developed electrospun polyethersulfone (ePES) macroencapsulation devices with controlled nanofibrous architecture to modulate host immune responses and enhance graft protection. Biocompatibility and immunoprotective properties of ePES-based macroencapsulation devices were first evaluated in rats over five weeks. To assess their potential for cell transplantation and immune isolation, ePES-based devices encapsulating allogeneic islets were implanted in vivo in rats. The ePES membranes exhibited immunomodulatory properties by suppressing monocyte-to-macrophage differentiation and limiting infiltration of activated macrophages, thereby mitigating early foreign body responses (FBRs). Encapsulated islets, maintained viability and exhibited glucose-responsive insulin secretion in vitro. Following peritoneal implantation in rats, ePES devices containing allogeneic islets demonstrated excellent biocompatibility, achieved effective immunoisolation, minimal fibrosis, and favorable host integration over five weeks without immunosuppression. Explanted devices retained functional insulin secretion, confirming graft survival. Collectively, these findings establish ePES-based macroencapsulation as a robust platform for immunoprotected endocrine cell transplantation.