Biomimetic Gelatin‐Based 3D Scaffolds for Enhanced Islet Microencapsulation and Functionality in Diabetes Therapy

Tissue-engineered scaffolds are increasingly important for improving pancreatic islet transplantation, as conventional transplantation disrupts the pancreas's native vasculature and extracellular matrix, reducing islet viability and function. This underscores the need to develop a three-dimensional porous microencapsulation scaffold system that can replicate a supportive microenvironment, providing both mechanical stability and biological cues vital to preserving islet viability and function. This study investigated the potential of two freeze-dried and crosslinked gelatin-based scaffolds: Gelatin vinyl acetate copolymer (GeVAc) and gelatin with oxidized dextran dialdehyde (GELDEX), for supporting pancreatic islet culture. Their physicochemical properties, architecture, and wettability were analyzed using scanning electron microscopy and contact angle measurements. Both scaffolds exhibited hydrophilic, biocompatible, and structurally stable characteristics. Mouse pancreatic MIN6 cells were cultured on the scaffolds for 7 days to evaluate islet viability, extracellular matrix deposition and functionality through immunocytochemistry, glucose-stimulated insulin secretion (GSIS), and gene expression analysis. MIN6 cells adhered well to both scaffolds, forming dense monolayers and multicellular spheroids that resembled native islet clusters. GeVAc scaffolds showed significantly higher glucose sensitivity and glucose stimulation index (GSI) compared to GELDEX. While INS1 and PDX1 expression levels were comparable in both scaffolds, NKX6.1 expression was significantly higher in GeVAc. These findings indicate that scaffold architecture and surface characteristics play a crucial role in creating a supportive microenvironment for islet cluster formation, highlighting the potential of gelatin-based scaffolds as microencapsulation platforms for clinical islet transplantation in diabetes therapy.