Tri‐Layer Citrate‐Based Hydroxyapatite Composite Scaffold Promoting Osteogenesis and Gingival Tissue Regeneration for Periodontal Bone Defect Repair

Periodontal bone defect (PBD) treatment involving oral soft and hard tissues is complicated and high requirements for regenerated materials. Besides osteogenic effects, the materials are also required to have the function of barrier soft tissues and promote wound healing. Citrate is reported to promote bone formation through enhanced osteoinductivity and facilitate wound healing by enabling phased angiogenesis. Herein, a novel tri-layered citrate-based hydroxyapatite (Ci-HA) composite scaffold that serves as a bone substitute is developed by "one-pot" method for PBD treatment. It is found that Ci-HA degradation products can promote the osteoblastic differentiation of rat bone mesenchymal stem cells and human periodontal ligament stem cells and upregulate angiogenesis-related gene expression in human gingival fibroblasts. Moreover, 3D remodeling in vitro shows that an intermediate layer of tri-layered Ci-HA composite scaffold acts as an optimal barrier. In vivo evaluation of Ci-HA in a rat periodontal intrabony three-wall defect model shows significantly increased bone formation with markedly enhanced osseointegration and better wound healing properties similarly with commercial Bio-Oss bone powder and Bio-Gide membrane. Thus, the novel tri-layered Ci-HA composite scaffold with high biocompatibility may represent a promising biomaterial with multi-effective bone regeneration, barrier effect, and wound healing capacity in the treatment of PBD.