Osteoarthritis (OA) is a leading cause of physical disability among aging populations, with no available drugs able to efficiently restore the balance between cartilage matrix synthesis and degradation. Also, OA has not been accurately classified into subpopulations, hindering the development toward personalized precision medicine.In the present study, we identified a subpopulation of OA patients displaying high activation level of epidermal growth factor receptor (EGFR). With Col2a1-creERT2; Egfrf/f mice, it was found that the activation of EGFR, indicated by EGFR phosphorylation (pEGFR), led to the destruction of joints. Excitingly, EGFR inhibition prohibited cartilage matrix degeneration and promoted cartilage regeneration. The Food and Drug Administration (FDA)-approved drug gefitinib could efficiently inhibit EGFR functions in OA joints and restore cartilage structure and function in the mouse model as well as the clinical case report.Overall, our findings suggested the concept of the EGFR activated OA subpopulation and illustrated the mechanism of EGFR signaling in regulating cartilage homeostasis. Gefitinib could be a promising disease-modifying drug for this OA subpopulation treatment.

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Corneal transplantation is the widely accepted treatment to restore sight for corneal blindness. To date, because of the global donor cornea shortage, there is a need for alternatives to human donor corneas. Biocompatible collagen is an excellent candidate material for corneal repair in the view of biomimetics. Herein a class of polyrotaxane multiple aldehyde (PRA) crosslinkers based on the host−guest supramolecules of α-cyclodextrins and poly(ethylene glycol) is prepared to cross-link with collagen to fabricate materials for corneal repair. Aldehyde groups from rotaxanes and α-cyclodextrin units can synergistically improve the mechanical and optical properties of PRA cross-linked collagen membranes (Col-PRAs). Compared with counterparts cross-linked by traditional a cross-linker of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide and N-hydroxy-succinimide, Col-PRAs have better mechanical properties, especially suture resistance as well as optical properties. In vivo lamellar keratoplasty results indicate that Col-PRAs not only can bear tight suturing on a rabbit cornea but also are prone to the remodeling of the epithelium and stroma of the cornea due to the outstanding cell adhesion and proliferation. These novel Col-PRAs exhibit great potential for use in the corneal regeneration.