Design and characterization of ferulic acid-releasing alginate dialdehyde-gelatin hydrogel for islet cell encapsulation.

Diabetes treatment faces significant challenges due to immune rejection and oxidative stress that impair islet cell viability and function after transplantation. This study presents the development and in vitro evaluation of an injectable ferulic acid (FA)-loaded alginate dialdehyde-gelatin (ADAG) hydrogel designed to enhance islet cell survival and functionality by providing a protective, bioactive microenvironment. FA was incorporated at an optimized concentration (2500 μM) into the ADAG hydrogel matrix, and its successful integration was confirmed by Raman spectroscopy. The FA/ADAG hydrogel demonstrated rapid gelation within 4-5 min, a crucial feature for minimally invasive injectable delivery and in situ scaffold formation. Its porous, interconnected microstructure supports efficient nutrient and oxygen diffusion, essential for maintaining islet viability. With high water uptake capacity, the hydrogel sustains a hydrated environment conducive to cell survival, while its compressive strength of 420 ± 32 kPa provides mechanical stability to protect encapsulated islets without compromising tissue compliance. Importantly, the hydrogel enables sustained FA release, offering continuous antioxidant protection to counteract oxidative stress, a major challenge in islet transplantation. The FA/ADAG system also exhibited excellent cytocompatibility, immunocompatibility, and hemocompatibility. Consequently, MIN6 cells encapsulated within the FA/ADAG hydrogel showed significantly enhanced proliferation and survival over seven days, along with improved glucose-stimulated insulin secretion compared to FA-free ADAG hydrogels. Furthermore, the hydrogel displayed strong free radical scavenging activity, indicating its potential to mitigate oxidative stress in islet transplantation. These findings suggest that FA/ADAG hydrogels offer a promising injectable platform for islet encapsulation with protective properties beneficial for diabetes therapy.