Soft, curved and transparent fish scale biocornea for anterior lamellar keratoplasty

Due to structural and compositional similarities with human corneas, decellularized fish scale scaffolds have emerged as potential substitutes for donor corneas. However, to date, their effective use in anterior lamellar keratoplasty has rarely been reported, as their rigid texture and poor conformity to the curved corneal bed can cause graft-host mismatch and sustained mechanical irritation. To overcome these limitations, this study introduced a softening strategy to convert rigid decellularized fish scales into soft and curved matrices. A subsequent mild crosslinking treatment stabilized the softened structure and yielded fish scale biocorneas (FSBCs). The softening process was associated with partial weakening of noncovalent interactions within the extracellular matrix. This strategy simultaneously improved mechanical compliance, curvature conformity and optical transparency while preserving the ordered collagen framework. The resulting FSBCs exhibited compressive elastic modulus and light transmittance comparable to those of human corneas. Moreover, FSBCs demonstrated suitable nutrient permeability, supported corneal cell adhesion and proliferation and displayed improved tissue biocompatibility in subcutaneous implantation. In a three-month rabbit anterior lamellar keratoplasty model, FSBCs showed good conformity to the corneal bed and favorable graft-host integration, facilitated complete epithelialization and restored stromal thickness to near-normal levels. Overall, this study addresses the mechanical and morphological limitations of conventional fish scale scaffolds, offering a promising option for lamellar corneal transplantation. STATEMENT OF SIGNIFICANCE: Corneal transplantation is the gold standard for treating irreversible corneal blindness, but its use is limited by donor shortage. Fish scales exhibit compositional and structural similarities to the human corneas, but conventional decellularized fish scale scaffolds are mechanically rigid and morphologically mismatched with the curved corneal bed, which limits their application in anterior lamellar keratoplasty. This study presents a simple softening-and-shaping strategy to convert fish scales into soft and curved biocorneas. The resulting biocorneas showed cornea-like mechanical and optical properties and supported corneal repair in a rabbit model. This study provides a promising option for anterior lamellar keratoplasty and may also offer a useful reference for regulating the structure and mechanical properties of other collagen-based biomaterials.