Rapidly mineralizing injectable dense collagen gels simultaneously fibrillized and functionalized through bioactive...

Without functionalization, reconstituted collagen gels demonstrate poor mineralization in vitro and in vivo. Due to their high reactivity, bioactive sol-gel-derived borate-glasses (SGBGs) rapidly convert to carbonated hydroxyapatite (CHA) in vitro. This mineralization is associated with an increase in pH upon SGBG dissolution, a feature that can simultaneously fibrillize and functionalize injectable collagen hydrogels. In this study, a facile fabrication process was used to self-assemble acid-solubilized collagen molecules in the presence of rapidly dissolving SGBGs, generating highly hydrated collagen gels. These precursor fibrillar gels were compacted through gel aspiration-ejection to fabricate injectable SGBG-functionalized dense collagen gels. The resulting bone extracellular matrix-mimicking gels exhibited fibrillar mineralization within 2 hours in simulated body fluid, and by day 7, CHA formation approached native bone levels. In turn, the progressive increase in mineralization induced a significant increase in matrix stiffness. This in vitro rapid mineralization rate was reflected in vivo, when acellular SGBG-dense collagen gels were directly injected into unicortical critical-size defects in rat tibia and monitored over 2 weeks. Micro-CT analysis showed that bone volume fraction was significantly higher in functionalized gels compared to neat dense collagen gels. Complementary histological von Kossa, Toluidine blue, and alkaline phosphatase staining were performed on recovered tissue sections to investigate the early potential of nascent bone formation. Compared to neat gels, the histology of SGBG-dense collagen gels revealed higher levels of positive mineral staining, accompanied by increasing levels of host cell infiltration and osteoblastic activity. In summary, the immediate functionalization and rapid mineralization capacity endows these SGBG-dense collagen gels promise in bone tissue repair and engineering.