Bioinspired Tissue Transparency: Achieving Sclera-to-Cornea Transplantation

Human soft tissues have significant clinical potential for corneal repair, yet their therapeutic efficacy is limited by inherent opacity. This study introduces a bio-inspired decellularization-compression-locking tactic (DCLT) for tissue clearing. The DCLT leads to long-term transparency (>80% light transmittance) of biological soft tissues while preserving native bioactivity by removing light-scattering subcellular structures and regulating extracellular matrix fiber density. This distinguishes it from traditional reagent-mediated tissue-clearing approaches. Using DCLT, transparent decellularized human sclera (hTDS) is fabricated as a corneal substitute, integrating advantages of optical clarity, mechanical reinforcement, and resistance to swelling and enzymatic degradation. hTDS promotes wound healing and restores optical function in models of complex corneal injuries, including alkali burns, acute edematous-phase keratoconus, and open-globe injuries. Notably, its anti-angiogenic and anti-fibrotic efficacy are superior to those of donor corneas in ocular surface with chronic inflammation. This study establishes a simple, effective, and safe tissue-clearing strategy and provides a promising tissue engineering solution for allogeneic corneal transplantation.