Introduction Even though the cornea is one of the most widely transplanted solid tissues, it is estimated that approximately 98% of patients requiring a transplant lack access to this sight-saving procedure. This critical gap is a direct consequence of a tremendous global donor shortage, highlighting the urgent need for bioengineered alternatives. Despite significant research efforts, creating a functional bioengineered cornea remains a major challenge. The present study investigates a novel biomimetic approach leveraging Plasma Rich in Growth Factors (PRGF) technology in combination with dental pulp stem cells.Material and methodsHuman dental pulp stem cells (hDPSCs) were isolated, characterized, and differentiated into epithelial, stromal, and endothelial corneal phenotypes. Two distinct types of corneal grafts were developed, categorized by the differentiation stage of the incorporated hDPSCs. The bioengineered constructs consisted of a central bioactive PRGF-fibrin core embedding cells and sandwiched between a trilaminar anterior layer and a posterior cell sheet. The PRGF-derived supernatant was utilized as a medium supplement. The resulting corneal substitutes were evaluated for their optical and rheological properties, as well as cellular viability. Finally, the structural stability and remodeling kinetics of the bioengineered grafts were histologically examined and quantified.ResultsCorneal grafts incorporating undifferentiated hDPSCs exhibited superior elasticity and transparency, while maintaining a higher cell density following the fabrication process. The more pronounced mass reduction observed in these constructs was concomitant with accelerated fibrin degradation and enhanced de novo collagen synthesis.ConclusionBioengineered grafts comprising a central PRGF membrane fibrin core integrated with hDPSCs to mimetically replicate the trilaminar cellular architecture of the cornea, represent a dynamic biomimetic candidate for future clinical applications in corneal transplantation surgery.