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UV-cured collagen-based hydrogels hold promise in skeletal muscleregeneration due to their soft elastic properties and porous architecture.However, the complex triple helix conformation of collagen and environmentalconditions, i.e. molecular oxygen, pose risks to reaction controllability,wet-state integrity and reproducibility. To address this challenge, aphoto-click hydrogel platform is presented through an oxygen-insensitivethiol-ene reaction between 2-iminothiolane (2IT)-functionalized type I collagenand multi-arm, non-homopolymerizable norbornene-terminated polyethylene glycol(PEG). UV-induced network formation is demonstrated by oscillatory time sweepson the reacting thiol-ene mixture, so that significantly increased storagemoduli are measured and adjusted depending on the photo-initiatorconcentration. Variations in PEG functionality (4-arm and 8-arm) and PEGcontent generate hydrogels with skeletal muscle native stiffness (Ec= 1.3-11.5kPa), diffusion-controlled swelling behavior and erosion-driven degradability.In vitro, no cytotoxic effect is detected on C2C12 murine myoblasts, whilemyogenic differentiation is successfully accomplished on hydrogel-seeded cellsin low serum culture medium. In vivo, 7-day subcutaneous implantation ofselected thiol-ene hydrogel in rats reveal higher cell infiltration, bloodvessel formation, and denser tissue interface compared to a clinical goldstandard collagen matrix (Mucograft, Geistlich). These results thereforesupport the applicability and further development of this hydrogel platform forskeletal muscle regeneration.

A photo-click thiol-ene collagen-based hydrogel platform for skeletal muscle tissue engineering