Gelatin scaffold with multifunctional curcumin-loaded lipid-PLGA hybrid microparticles for regenerating corneal endothelium

Highlights: • Lipid-PLGA hybrid microparticles can release curcumin in a sustained manner. • Curcumin exhibits a pro-proliferative effect on corneal endothelial cells. • Curcumin protects corneal endothelial cells against oxidative stress. • Scaffold with curcumin-loaded microparticles supports corneal endothelium formation. Corneal transplantation is currently the only approach to cure corneal blindness. Cell-based strategies that employ corneal endothelial cells (CECs) grown on supporting biomaterials hold great promise as possible alternative therapies for treating corneal endothelial dysfunction. Nevertheless, most biomaterials are used merely because of their robust mechanical properties, providing passive physical support for the transplantation of CEC monolayers. Based on the versatility of curcumin in ophthalmic applications, this study aims to develop a multifunctional scaffold system that can not only support the function and transplantation of CECs but also prevents post-engraftment complications by sustained curcumin release, thus enhancing the long-term success of CEC engraftment. Curcumin-loaded lipid-poly(lactic-co-glycolic acid) (PLGA; Cur@MPs) hybrid microparticles (MPs) fabricated using an oil-in-water single emulsion method are embedded into gelatin-based scaffolds. The anti-inflammatory, antioxidative, and anti-angiogenic potentials of the developed scaffolds and their capacity in supporting CEC monolayer formation are evaluated. The Cur@MPs are capable of promoting CEC proliferation, protecting CECs from oxidative stress-induced cell death via modulating Nrf2/HO-1 signaling axis, suppressing the secretion of pro-inflammatory cytokines by macrophages, and inhibiting the migration and angiogenesis of vascular endothelial cells. By incorporating the Cur@MPs into a thin gelatin membrane, the fabricated scaffold is able to support the growth and organization of CECs into a polygonal morphology with tight junctions. These experimental results demonstrate the potential of the Cur@MPs-loaded gelatin scaffold for actively supporting the survival and function of CEC monolayers after transplantation.