Decellularized corneal-based 3D scaffolds: methods decellularization, characterization, mechanical properties, and species source.

Corneal blindness is a significant worldwide health issue owing to low number of global corneal donors. Decellularized corneal scaffolds intend to be a promising choice for corneal repair by maintaining the native extracellular matrix (ECM) while minimizing immune reactions. This effort comprehensively reviews various decellularization strategies such as physical, chemical, and biological methods and their impact on ECM integrity, transparency, and mechanical strength. We explored source tissues such as porcine, human, and SMILE-derived lenticules based on their structure similarity and clinical suitability. Characterization techniques including immunohistochemical, histological, mechanical, and in vivo assessments are reviewed to evaluate scaffold quality and biocompatibility. Recellularization approaches which restore corneal functionality, using epithelial, stromal, and endothelial cells also have been investigated. Additionally, progresses in composite biomaterials and 3D bioprinting utilizing decellularized corneal matrices are highlighted, showing enhanced transparency, adhesion, and regenerative potential. Despite clinical progress which is evidenced by successful preclinical studies and clinical trials, some challenges such as protocols optimization, large-scale production, and integration with host tissue remain. Further integrated research is essential to optimize scaffold design, ensure long-term safety, and establish decellularized corneas as a possible solution to the scarcity of donor tissues for transplantation.