Photocrosslinkable injectable glycol chitosan/gelatin biohybrid thermogel as a localized delivery platform for bone regeneration.

Abstract

Injectable thermogels provide a minimally invasive strategy for localized biomaterial delivery, but insufficient mechanical stability and limited cell-adhesive properties often hinder regenerative performance. Here, we developed a photocrosslinkable injectable biohybrid thermogel by blending methacrylated glycol chitosan (MGC) with gelatin methacryloyl (GM). The MGC/GM precursor exhibited a flowable temperature window for syringe injection, followed by thermo-induced gelation at physiological temperature and UV-triggered covalent crosslinking for in situ mechanical stabilization. The photocrosslinked hydrogels showed enhanced compressive strength (39-71 kPa) compared to MGC alone (28-34 kPa), reduced swelling, and prolonged degradation (∼54-58% mass remaining after 30 days). The biohybrid system maintained high cell viability (>90%) and promoted spheroid outgrowth due to GM-mediated cell-adhesive functionality. In a subcutaneous mouse model, the precursor was injected beneath intact dorsal skin and stabilized by transdermal UV irradiation, enabling stable gel retention without significant apoptosis or chronic inflammation. In a critical-size calvarial defect model, MGC/GM hydrogel was placed into the surgically exposed defect and photocrosslinked in situ as a localized delivery platform for hBMSCs and AB204, an activin A/BMP-2 chimera. This treatment enhanced bone regeneration, increasing bone volume fraction and mineralized tissue formation. These results demonstrate an injectable, mechanically tunable, and biofunctional thermogel platform for localized regenerative delivery.