Engineering tunable structure–property relationships in collagen/chitosan scaffolds via 3-glycidoxypropyltrimethoxysilane-mediated dual crosslinking for cartilage regeneration

Three-dimensional scaffolds for cartilage tissue engineering require mechanical integrity and controlled degradation while maintaining a bioactive microenvironment. Herein, 3-glycidoxypropyltrimethoxysilane was employed as a multifunctional organosilane crosslinker to construct collagen/chitosan hybrid scaffolds through epoxy ring-opening and siloxane condensation reactions, generating a covalently integrated organic–inorganic network. This dual crosslinking mechanism enabled tunable regulation of network connectivity and scaffold architecture. Silane incorporation significantly enhanced structural organization and thermal stability, reduced swelling and enzymatic degradation, and increased compressive stiffness in a controllable manner. Spectroscopic analysis confirmed the formation of Si–O–Si networks and polymer–silane linkages, establishing a direct correlation between crosslink density and mechanical reinforcement. Among the tested formulations, the hybrid scaffold exhibited an optimized structure–property profile, supporting sustained proliferation of human bone marrow-derived mesenchymal stem cells and human chondrocytes. Under chondrogenic induction, the engineered scaffold upregulated cartilage-specific markers and maintained elevated sulfated glycosaminoglycan production in a cell-type-dependent manner, demonstrating effective coupling between mechanical adaptation and biological functionality. This work establishes an engineering-oriented framework linking GPTMS-mediated hybrid network regulation with tunable structure–property–biofunction relationships, providing a rational strategy for designing mechanically adaptive organic–inorganic hybrid scaffolds for cartilage tissue engineering. The present study primarily focuses on establishing the fundamental structure–property–biofunction relationships of the hybrid scaffolds through comprehensive physicochemical and in vitro biological evaluations, thereby providing a mechanistic basis for subsequent in vivo investigation and translational development.