Rapidly mineralizing injectable dense collagen gels simultaneously fibrillized and functionalized through bioactive sol–gel borate-glass hybridization

This study developed injectable dense collagen gels that simultaneously undergo collagen fibrillization and functionalization through incorporation of highly reactive sol-gel-derived borate glass particles for bone tissue repair. B46-SGBG particles were mixed directly with acidic type I collagen solutions, where rapid glass dissolution increased local pH and induced collagen fibrillization without conventional NaOH neutralization. The resulting highly hydrated precursor gels were compacted using gel aspiration-ejection to create dense, injectable collagen scaffolds that mimic aspects of bone extracellular matrix. Hybrid gels mineralized rapidly when immersed in simulated body fluid, with carbonated hydroxyapatite formation detectable within 2 hours. Mineral accumulation progressed over time, and by day 7 the inorganic content of the hybrid gels approached approximately 70 wt%, comparable to the mineral fraction of native bone and dentin. This mineralization substantially altered scaffold mechanics: Hybrid-7.4 gels showed significant increases in compressive modulus of approximately 48% after 7 days and 137% after 14 days in simulated body fluid, whereas Neat-7.4 collagen controls showed no significant stiffness change. In vivo, acellular Hybrid-7.4 and neat collagen gels were directly injected into critical-size unicortical rat tibial defects. Micro-CT and histological analyses showed greater mineralization in the borate-glass-functionalized gels, with significantly higher bone volume by week 2 and significantly greater von Kossa-positive mineral deposition at both one and two weeks. Host cell infiltration increased over time in both materials, and osteoblastic activity was observed at the gel-defect interface. Overall, the study demonstrates that borate-glass hybridization can simultaneously fibrillize, functionalize, rapidly mineralize, and mechanically reinforce injectable dense collagen scaffolds for bone regeneration.