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bioRxiv · 10.64898/2026.04.13.718180

Photocrosslinkable silk fibroin-hyaluronic acid hybrid hydrogels enable chondrocyte-driven matrix deposition and mechanical maturation for cartilage tissue engineering

Rasoulian, F.·Ghaffari-Bohlouli, P.·Otahal, A.·Bauer, C.·Shahabi Nejad, M.·Klein, M.·Shavandi, A.·Heydari, A.·Nehrer, S.
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Abstract

Articular cartilage has limited self-repair capacity, and current treatments fail to fully restore its structure and function. 3D hydrogels that support chondrocyte viability and extracellular matrix (ECM) deposition offer a promising strategy for cartilage regeneration. Here, we developed a photo-crosslinkable silk fibroin-hyaluronic acid hydrogel for 3D encapsulation of primary human chondrocytes. Hydrogels were formulated with varying silk fibroin methacrylate (SilMA, 10-20% w/v) and hyaluronic acid methacrylate (HAMA, 1-2% w/v) concentrations and characterized for rheological, mechanical, and morphological properties. All SilMA-HAMA hydrogel formulations exhibited shear-thinning behavior and rapidly gelled (<20 s) under UV irradiation while maintaining high porosity, thereby ensuring injectability and efficient nutrient diffusion. Notably, the Youngs modulus of the cell-laden scaffolds increased from [~]18 kPa to [~]1200 kPa over culture, indicating mechanical maturation driven by chondrocyte-mediated matrix deposition. This maturation was further confirmed by histological analysis and qPCR, which demonstrated enhanced ECM production and chondrogenic gene expression. Taken together, these results highlight SilMA-HAMA hydrogels as a promising biomimetic platform that couples mechanical reinforcement with biological functionality for cartilage tissue engineering.

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Rasoulian, F., Ghaffari-Bohlouli, P., Otahal, A., Bauer, C., Shahabi Nejad, M., Klein, M., Shavandi, A., Heydari, A., Nehrer, S.. 2026-04-15. Photocrosslinkable silk fibroin-hyaluronic acid hybrid hydrogels enable chondrocyte-driven matrix deposition and mechanical maturation for cartilage tissue engineering. https://doi.org/10.64898/2026.04.13.718180

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