An Injectable, Osteoconductive Gelatin-Enabled GelMA/HAp Hydrogel Scaffold for Minimally Invasive Bone Tissue Engineering

Despite extensive exploration of gelatin methacryloyl (GelMA)-based hydrogels for bone tissue engineering, their clinical translation is hindered by a critical trade-off: poor precursor stability leads to rapid sedimentation of bioactive fillers like hydroxyapatite (HAp), while formulations optimized for injectability often sacrifice mechanical integrity or handling precision. To overcome this challenge, we report a rheologically engineered, injectable composite hydrogel scaffold that integrates unmodified gelatin as a thermoresponsive viscosity modulator into a GelMA/HAp matrix. The incorporation of gelatin yields a stable, paste-like precursor at physiological temperature, which effectively prevents HAp sedimentation and enables precise, filamentous extrusion. Subsequent UV crosslinking locks the homogeneous structure in place, resulting in a mechanically robust scaffold with significantly enhanced compressive modulus. In vitro studies demonstrate that this biomimetic microenvironment not only supports high viability and proliferation of bone marrow stromal cells (BMSCs) but also potently enhances their osteogenic differentiation, as evidenced by upregulated alkaline phosphatase activity, Runx2 expression, and matrix mineralization. This simple, one-step strategy successfully reconciles injectability, structural fidelity, and bioactivity, offering a highly promising and clinically translatable platform for minimally invasive bone regeneration.