# Gamma Irradiation of Poly(lactide‐co‐glycolide) Scaffolds Reduces the Mechanical Stability and Function of Islet Grafts in Diabetic Nonhuman Primates

## TL;DR

Gamma irradiation weakens scaffolds used for islet transplantation in diabetic primates, affecting graft stability and function.

## Contribution

The study identifies how gamma irradiation impacts scaffold mechanical properties and proposes adjustments to improve islet graft outcomes.

## Key findings

- Gamma-irradiated scaffolds showed fragility during seeding and implantation.
- A PLG:NaCl ratio of 1.15:30 balanced mechanical stability and islet compatibility in mice.
- Scaffold porosity adjustments can mitigate sterilization effects on transplantation.

## Abstract

Clinical islet transplantation has long been investigated as a potential cure for type 1 diabetes (T1D), yet standard intrahepatic delivery leaves islets prone to an instant blood‐mediated inflammatory response. Herein, we investigated the design of microporous poly(d,l‐lactide‐co‐glycolide) (PLG) scaffolds for extrahepatic islet transplantation in mouse and nonhuman primate (NHP) models. Acellular scaffolds elicited only a mild inflammatory response following implantation into the omentum. On scaffold islet transplantation had extensive insulin staining at 4 weeks yet modest insulin requirement reductions in diabetic NHP recipients. Scaffolds were sterilized by irradiation and exhibited fragility during seeding and implantation, motivating an increase in the manufacturing ratio of PLG:NaCl from 1:30 to 1.25:30 w/w. These scaffolds exhibited no differences in porosity or interior geometry between sterilization conditions, and transplants in mice restored normoglycemia. We piloted a modified scaffold study in a fourth NHP, and although scaffold integrity was improved, the transplant outcome was similar. We subsequently tested intermediate PLG:NaCl ratios in mice, finding that a 1.15:30 ratio achieved a balance of mechanical stability and islet compatibility. Overall, these studies identify that scaffold porosity can be adjusted to account for the impact of sterilization on transplantation.