Harnessing Starch for Next-Generation Corneal Tissue Engineering

Corneal transplantation is the gold-standard treatment for end-stage corneal disease. However, its clinical use is limited by the global shortage of donor tissue, risks of immune rejection, and postoperative complications. Corneal tissue engineering (CTE) has emerged as a promising alternative strategy, focusing on the development of biocompatible scaffolds that support cellular regeneration while maintaining the critical optical clarity and biomechanical properties of the native cornea. Starch (ST), a naturally derived and abundant polysaccharide, has garnered significant interest as a biomaterial for this application due to its inherent biocompatibility, tunable biodegradability, and amenability to chemical modification. Its physicochemical properties, including controllable hydration, intrinsic optical transparency, and modifiable mechanical strength, are highly conducive to corneal scaffold design. ST can be processed via various techniques such as hydrogel formation, electrospinning, and three-dimensional (3D) bioprinting, to generate structures tailored for specific corneal repair applications. Recent advances focus on functionalizing ST-based scaffolds with bioactive molecules to enhance cellular adhesion and proliferation, improve biomechanical performance, and better recapitulate the native corneal extracellular matrix (ECM). Moreover, ST offers considerable economic and environmental advantages over synthetic polymers due to its cost-effectiveness and sustainable sourcing. Notwithstanding its potential, key challenges persist in optimizing its long-term mechanical stability, controlling its degradation profile to match tissue ingrowth, and ensuring seamless biointegration with host corneal cells. This review provides a comprehensive analysis of the fabrication methodologies, structure-property relationships, and in vitro and in vivo performance of ST-based biomaterials in the context of CTE. Given its versatility and favorable characteristics, ST represents a highly promising substrate for advancing next-generation corneal regenerative therapies.