Nanofibrous Bioabsorbable Functionalized Scaffolds Augment Subcutaneous Islet Engraftment and Function in Mice

The subcutaneous (SQ) space is a promising site for islet transplantation to treat type 1 diabetes. We hypothesize that nanofibrous bioabsorbable functionalized scaffolds (BAFS) implanted in the SQ space will create a highly vascularized niche that will support islet engraftment. Electrospun poly(lactic-co-glycolic acid) (PLGA) and gelatin (G) (PLGA + G) scaffolds functionalized with vascular endothelial growth factor (V) and laminin (L) were wrapped around a nylon catheter and implanted into the SQ space of immunodeficient mice. Experimental groups included PLGA, PLGA + G, PLGA + G + V + L, and the device-less catheter alone. The degree of vascularization in these sites was assessed 4 weeks after implantation, and in a separate cohort of mice, neonatal porcine islets (NPIs) were transplanted subcutaneously into diabetic mice. NPIs transplanted under the kidney capsule served as controls. PLGA + G + V + L recipients showed enhanced vascularization, with a higher number of cells positive for lectin, smooth muscle actin, and CD31 compared with other groups (P < 0.05). Recipients of PLGA + G + V + L scaffolds and NPIs achieved normoglycemia faster (P < 0.05) and exhibited higher serum porcine insulin levels (P < 0.05) compared with all other groups. Our nanofibrous BAFS (PLGA + G + V + L) significantly vascularized the SQ space and supported long-term islet graft survival, suggesting a clinically relevant and tunable alternative site for β-cell replacement therapies.

This study highlights how bioabsorbable functionalized scaffolds (BAFS) create a subcutaneous vascularized niche that supports islet graft function. BAFS exhibit sustained release of vascular endothelial growth factor and laminin, which promoted enhanced vascularization in the subcutaneous space. Additionally, these vessels are mature and patent as evidenced by intraluminal cells positive for lectin and smooth muscle actin. BAFS transplanted with neonatal porcine islets achieved normoglycemia faster and exhibited higher serum porcine insulin levels than all other groups. Overall, BAFS transplanted with neonatal porcine islets facilitates long-term islet graft function and corrects diabetes in mice, suggesting a clinically relevant and tunable alternative site for β-cell replacement therapies.