High-Resolution 3D Bioprinted Hydrogel Scaffolds Enable Sustained Intraperitoneal Cell Delivery

Intraperitoneal (I.P.) delivery of cell-based therapeutics represents a promising strategy for treating regional peritoneal diseases; however, rapid cellular clearance severely limits therapeutic durability. A critical unmet need is the development of implantable biomaterial platforms that can both mechanically integrate within the dynamic I.P. cavity and sustain viable cell persistence in vivo. Here, we establish a Continuous Liquid Interface Production (CLIP)-based 3D bioprinting strategy to engineer transplantable, cell-laden hydrogel scaffolds optimized for I.P. implantation. Through systematic bioresin design, we identify a GelMA-PEGDA formulation that achieves a balance between high-resolution printability, tissue-matched mechanical characteristics (Young's modulus 10-15 kPa), and controlled biodegradation (~75% mass loss over 14 days). The resulting constructs support sustained cell viability and proliferation for over 30 days in vitro. Importantly, in an animal study conducted in 6-8 weeks of female nude mice, in vivo I.P. implantation demonstrates a ~10-fold extension in cellular persistence compared to direct cell injection, prolonging the time to 50% signal decay from ~3 days to ~30 days, with detectable cell retention approaching two months in select animals. The platform further accommodates multiple clinically relevant cell types, including human mesenchymal stem cells and neural stem cells, highlighting its translational versatility. Collectively, this work defines key material and architectural parameters required for I.P. implantable cell therapeutics and establishes CLIP-based bioprinting as a scalable strategy for regional delivery of living therapeutics.