*Purpose: Maintenance of human islet viability and function ex vivo can be a significant bottleneck for both regenerative medicine as well as tissue engineering applications. A strategy that seeks to combine the biophysical and mechanical properties of inert encapsulation materials like alginate with the peri-islet niche provided by extracellular matrix (ECM)-derived biomaterials, could provide a physiomimetic pancreatic microenvironment for maintaining long-term human islet viability and function in culture.

*Methods: We have recently developed an innovative, detergent-free, DI water-based protocol for the decellularization of human pancreas and production of human pancreatic decellularized extracellular matrix (dECM). This decellularization method is adept at retaining the matrisome, while clearing out cellular proteins. In order to test the effect of the resulting dECM on the viability and function of pancreatic cells, primary human islets were embedded in dECM-alginate capsules and cultured for 58 days. Glucose-Stimulated Insulin Secretion (GSIS), morphology and live/dead imaging were performed on days 5, 9, 19, 33, 44 and 58 of culture.

*Results: It was found that incorporating dECM (0.1 mg/ml) within alginate microcapsules provides biochemical cues essential for maintaining long-term islet morphology, viability and function. Results indicated a significant increase in Glucose Stimulation Index (GSI) and total secreted insulin in islets encapsulated in dECM-alginate capsules, compared to control groups – free islets and islets encapsulated in dECM-free alginate, starting on day 33 of culture. Moreover, islets in dECM-alginate capsules maintained GSI levels similar to that observed in free islets at the first time point. The dECM was also tested in vitro with respect to nanosafety and it was found to exhibit excellent hemocompatibility, immunocompatibility and cytocompatibility.

*Conclusions: Therefore, it can be concluded that the human pancreatic dECM is biocompatible and its addition within alginate capsules preserves the ability of human islets to produce insulin in a glucose-responsive manner over long-term culture.

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