Background: Intrahepatic islet transplantation restores insulin independence but is limited by donor scarcity, immunosuppression, and poor engraftment due to instant blood-mediated inflammatory reaction and inadequate vascularization. Subcutaneous transplantation is safer but hindered by hypoxia and slow revascularization. Hydrogels provide structural support but restrict cell migration, while cryogels, with large, interconnected pores, show promise but struggle to replicate native extra-cellular matrix (ECM) and support vascularization. Placenta-derived cryogels can closely mimic islet ECM, offering a promising alternative.

Methods: This study tested whether placenta-derived cryogels enhance islet transplantation outcomes by supporting islet survival and function. Hydrogels from human placenta were blended in varying ratios and crosslinked at subzero temperature into cryogels. Quality assessments included DNA quantification, structural integrity, and LC-MS/MS protein analysis. Pore interconnectivity, porosity, density, and water swelling capacity were measured. Rat (100 IEQ, n=4) or human islets (50 IEQ, n=3) were seeded on cryogels, function was assessed using static incubation.

Results: Cryogels showed DNA removal, successful decellularization, and intact structure. Composition analysis revealed collagen and glycoproteins comparable to commercialized Matrigel®. Different hydrogel ratios showed no differences in interconnectivity, density, porosity, though higher Collagen I content increased water uptake significantly. By Day 14, islets on cryogels showed improved or stable stimulation index (SI) values (1.54±0.57 to 2.18±0.4), while conventional cultures declined (1.15 to 0.90) and Matrigel dropped sharply (2.12 to 0.60).

Conclusion: These results highlight human placenta-derived cryogels as a sustainable, biocompatible, and functional promising scaffold for improving islet transplantation outcomes, providing an animal-free alternative to matrices like Matrigel®.