Simona Casarella, Nicoletta Palmeri, Agata Grazia D’Amico, Assunta Virtuoso, Salvatore Saccone, Elisabetta Pricoco, Davide Scollo, Antonio Longo, Michele Papa, Francesca Boccafoschi, Velia D’Agata, Grazia Maugeri
Diabetes mellitus, a global epidemic, is a leading cause of blindness due to its detrimental effects on the retina, lens, and cornea. Diabetic keratopathy (DK), a significant ocular complication, severely compromises the corneal epithelium structure, barrier function, and healing capacity, largely driven by hyperglycemia-induced oxidative stress and apoptosis. Current therapeutic strategies for DK are limited and primarily symptomatic, failing to address underlying cellular deficits. This study investigates a novel regenerative approach utilizing a decellularized extracellular matrix (dECM) hydrogel functionalized with the neuroprotective peptide NAP (dECM hydrogel-NAP). Both dECM hydrogels and NAP have demonstrated promising regenerative and protective properties in various tissues, though their combined efficacy for diabetic corneal repair remains unexplored. Using a three-dimensional (3D) organotypic human corneal epithelium model of DK, we evaluated the therapeutic potential of dECM hydrogel-NAP to promote epithelial wound healing, restore barrier function, mitigate apoptotic responses, and support cellular viability under diabetic conditions. Our findings suggest that dECM hydrogel-NAP holds significant promise as a therapeutic strategy for supporting corneal epithelial regeneration in diabetic keratopathy.