Hierarchically Structured Aquatic Collagen–Hydroxyapatite Matrices for Targeted Alveolar Ridge Regeneration

Alveolar ridge preservation (ARP) following tooth extraction often relies on bone graft materials to maintain ridge dimensions and support subsequent implant placement. While xenografts such as deproteinized bovine bone mineral are commonly used, they are characterized by slow resorption and limited biological activity. Herein, "AquaGraft" is introduced, a fully resorbable, bioactive bone graft composite derived from bullfrog skin collagen and fish-scale hydroxyapatite, engineered into a dual-crosslinked, hierarchically porous structure. Ex vivo whole-blood hemostasis assays revealed significantly faster clot formation with AquaGraft compared to Bio-Oss^® Collagen. In canine model, AquaGraft showed complete resorption within 16 weeks, and supported continuous, mineralized bone bridging with no observable graft remnants. AquaGraft demonstrated equivalent ridge preservation performance to Bio-Oss^® Collagen, while offering a distinct advantage in promoting 3D vascular network formation, important for long-term graft integration. Quantitative imaging revealed comparable buccal ridge preservation (AquaGraft: 86.08% ± 3.82%, Bio-Oss^® Collagen: 87.24% ± 3.87%) and new bone formation (AquaGraft: 44.90% ± 4.63%, Bio-Oss^® Collagen: 54.91% ± 3.66%), despite AquaGraft's lower hydroxyapatite content. This suggests a more efficient coupling of mineral reinforcement with biological remodeling, facilitated by its collagen-rich, pro-regenerative matrix. Overall, these findings position AquaGraft as a clinically translatable, bio-resorbable and bioinstructive scaffold capable of guiding bone tissue regeneration.