Bacterial synthesis of personalized biomimetic biological cornea.

Abstract

Corneal transplantation is one of the most effective treatments for corneal blindness. However, aside from clinical donor shortage, matching the transparency, curvature, and mechanical properties of artificial corneal materials with autologous corneas is challenging. This study employs bacterial synthetic biology, combining a curvature-customized model with an aldehyde modification system to develop a personalized biomimetic biological cornea (DBC@L-Cel) with a nanofiber network structure and customizable curvature and morphology. Dialdehyde bacterial nanocellulose (DBC) achieves a transmittance of 91.91 %, with optical and mechanical properties matching those of natural corneas. The incorporation of human-derived corneal lenticule microparticles (L) and Celastrol (Cel) significantly enhances the biocompatibility, adhesiveness, and anti-scarring capabilities of DBC. <i>In vitro</i>, DBC@L-Cel reduces stromal fibrosis by inhibiting the AGE/RAGE/NF-κB and PI3K/AKT pathway and activates epithelial proliferation and adhesion by upregulating the Wnt/β-catenin pathway. <i>In vivo</i>, transplantation of DBC@L-Cel significantly promotes the repair and regeneration of both the corneal stroma and epithelium, enabling rapid scarless reconstruction of the damaged cornea in a large-scale rabbit corneal defect model. This bacterially synthesized, curvature-customized, and highly transparent biomimetic cornea offers an innovative alternative for personalized transplantation therapy in corneal blindness.