Biodegradable Cu/Sr Co-Doped Hydroxyapatite Composite for Bone Defect Reconstruction: An In Vivo Study

Abstract Bone defect repair remains a significant challenge in the clinic, particularly in complex ischemic situations. Conventional bone substitutes typically fail due to defect geometries, impaired blood supply, or unbalanced degradation in coordination with new bone formation. To address these limitations, we developed a bioactive, injectable bone void filler. It consists of a poly(vinyl alcohol)/sodium alginate (PVA/SA) composite loaded with copper (Cu), strontium (Sr), and codoped with low-crystallinity hydroxyapatite (HA) granules. Specifically, HA codoped with 1 mol % Cu and 4 mol % Sr was hydrothermally synthesized at 120 °C and incorporated into a double-network PVA/SA hydrogel. The regenerative capacity of this composite was then evaluated by implanting preformed cylinders into a nonload-bearing rat femoral defect model for 4 and 8 weeks. Bone regeneration and neovascularization were assessed using micro-CT and immunohistology. In vivo tests demonstrated that this composite is replaced by bone. Micro-CT and histological evaluations of the in vivo results showed that the Cu/Sr codoped composite enhanced bone defect repair accompanied by enhanced early neovascularization, supporting coordinated vascular and bone tissue regeneration. Lastly, histological staining revealed unique healing patterns characterized by “bridge-like” bone restoration and “island-like” regeneration, offering a promising option for treating complex bone defects.