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