Thermoplastic silk-plasticizer membranes for biodegradable artificial corneal endothelium

Corneal endothelial dysfunction (CED) induces stromal edema through aqueous influx, disrupting collagen organization and causing corneal opacity, with chronic cases progressing to fibrosis. As a major cause of corneal blindness, CED currently requires corneal transplantation for treatment. However, the scarcity of human donors necessitates the urgent development of artificial corneal endothelial transplant materials. Previously reported non-biodegradable polymer materials suffer from inadequate adhesion and poor water barrier efficiency, with long-term implantation potentially causing foreign-body reactions. To address these issues, we developed a silk fibroin (SF)-plasticizer composite membrane using spin coating and water-annealing techniques. Glycerol-plasticized SF membranes exhibit excellent transparency and flexibility, with water-annealing further enhancing mechanical strength for intraocular surgical implantation. The addition of glycerol imparts thermoplasticity to SF membranes, enabling the fabrication of membranes with appropriate intraocular curvature through thermoforming. In vitro hydrostatic pressure tests demonstrated that SF membranes can withstand pressures equivalent to maximum intraocular pressure for over 75 days without rupture or leakage. Ethylene oxide sterilization of SF membranes did not affect their cytocompatibility and transparency. When implanted in CED rabbit models, SF membranes adhered tightly to the corneal stroma, effectively preventing aqueous humor penetration while allowing nutrient diffusion. During the three-month observation period, minimal inflammatory and foreign-body reactions were observed, with peripheral endothelial cells migrating onto the SF membrane surface. Transcriptomic sequencing revealed that SF membranes maintain corneal transparency by suppressing inflammatory pathways, inhibiting fibrosis, and regulating extracellular matrix remodeling. As a novel biodegradable artificial corneal endothelial layer, SF membranes demonstrate significant clinical potential as a temporary treatment for CED, to buy time until a cell-based transplant can be performed, owing to their excellent transparency, surgical manipulability, aqueous humor barrier, and low foreign-body reaction.