Granular polyrotaxane microgels as injectable hydrogels for corneal tissue regeneration

Corneal diseases, a leading cause of global vision impairment, present challenges in treatment due to corneal tissue donor scarcity and transplant rejection. Hydrogel biomaterials in the form of corneal implants for tissue regeneration, while promising, have faced obstacles related to cellular and tissue integration. This study develops and investigates the potential of granular polyrotaxane (GPR) hydrogels as a scaffold for corneal keratocyte growth and transparent tissue generation. Employing host-guest driven supramolecular interactions, we developed injectable, cytocompatible hydrogels. By optimizing cyclodextrin (CD) concentrations in thiol-ene crosslinked PEG microgels, we observed improved mechanical properties and thermoresponsiveness while preserving injectability. These microgels, adaptable for precise defect filling, 3D printing or tissue culture facilitate enhanced cellular integration with corneal keratocytes and exhibit tissue-like structures in culture. Our findings demonstrate the promise of GPR hydrogels as a minimally invasive avenue for corneal tissue regeneration. These results have the potential to address transplantation challenges, enhance clinical outcomes, and restore vision.