Visible light-induced simultaneous bioactive amorphous calcium phosphate mineralization and in situ crosslinking of coacervate-based injectable underwater adhesive hydrogels for enhanced bone regeneration

The field of bone tissue engineering is vital due to increasing bone disorders and limitations of traditional grafts. Injectable hydrogels offer minimally invasive solutions but often lack mechanical integrity and biological functionality, including osteoinductive capacity and structural stability under physiological conditions. To address these issues, we propose a coacervate-based injectable adhesive hydrogel that utilizes the dual functionality of in situ photocrosslinking and osteoinductive amorphous calcium phosphate formation, both of which are activated simultaneously by visible light irradiation. The developed hydrogel formulation integrated a photoreactive agent with calcium ions and phosphonodiol in a matrix of tyramine-conjugated alginate and RGD peptide-fused bioengineered mussel adhesive protein, promoting rapid setting, robust underwater adhesion, and bioactive mineral deposition. The hydrogel also exhibited superior mechanical properties, including enhanced underwater tissue adhesive strength and compressive resistance. In vivo evaluation using a rat femoral tunnel defect model confirmed the efficacy of the developed adhesive hydrogel in facilitating easy application to irregularly shaped defects through injection, rapid bone regeneration without the addition of bone grafts, and integration within the defect sites. This injectable adhesive hydrogel system holds significant potential for advancing bone tissue engineering, providing a versatile, efficient, and biologically favorable alternative to conventional bone repair methodologies.