Introduction Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, requiring lifelong treatment. Macroencapsulation of pancreatic islets - whether of xenogeneic origin or stem cell-derived - offers a promising therapeutic approach for T1D by protecting transplanted cells from immune rejection while maintaining their viability and function. However, insufficient oxygen (hypoxia) and suboptimal biocompatibility remain significant challenges in closed encapsulation systems, restricting graft survival and overall transplantation success. This study proposes a modular encapsulation device design consisting of a microarrangement module, an oxygen-producing scaffold and a bioactive immunoisolating membrane. This strategy aims to improve islet oxygenation and implant engraftment to advance the long-term efficacy of cell-based T1D therapies.

Materials and Methods Pseudoislets of defined size were generated and microarranged in microwells fabricated by PDMS molding techniques. These microarranged pseudoislets were encapsulated in a modular 3D-printed device designed to reduce oxygen-diffusion distances containing an oxygen-releasing material consisting of calcium peroxide (CaO₂) embedded into poly(dimethylsiloxane) (PDMS), and sealed with a semipermeable membrane impregnated with bioactive molecules. To simulate physiological transplantation conditions, the devices were cultured under hypoxic oxygen levels (1% O₂). Oxygen measurements were performed at the membrane interface during culture. Pseudoislet function and viability were assessed via dynamic glucose-stimulated insulin secretion (GSIS) assays and fluorescein diacetate (FDA) and propidium iodide (PI) staining. For in vivo engraftment analysis, devices were implanted and vessel formation and macrophage response were evaluated.

Results Encapsulated pseudoislets maintained comparable viability and function under hypoxic conditions (1% O₂) compared to normoxia. In hypoxic culture conditions, oxygen-releasing disks increased oxygen levels to 4–11%, reaching values similar to the 6–12% measured in 20% O₂ cultures. Devices coated with glycosaminoglycan-starPEG hydrogel containing bioactive factors demonstrated good engraftment in vivo. CD31 staining confirmed successful vascularization in close proximity to the membrane surface.

Conclusions The proposed strategy of encapsulating size-homogeneous, evenly distributed pseudoislets in a modular device with integrated oxygen-producing material addresses the key limitations of current macroencapsulation systems for T1D treatment. The oxygen-producing scaffold supports islet oxygenation in early posttransplant time, while microarrangement improves islet survival at low oxygen conditions. The demonstrated favorable engraftment of the device further supports its potential to enhance islet survival and function.