A cortical bone-mimetic composite with sustained biomechanical stability and longitudinal osteo-guiding capacity for functional reconstruction of large segmental bone defects

The regenerative repair of critical-sized load-bearing bone defects remains challenging in achieving stable graft fixation and timely restoration of biomechanical integrity without excessive biotherapeutics. Here, we develop a biomimetic polyamino acid/nanohydroxyapatite/high-strength/high-modulus polyvinyl alcohol fiber composite for critical-size load-bearing bone defect repair. The composites have good interfacial compatibility and cortical bone-matching mechanical strength. <i>In vitro</i> and <i>in vivo</i> studies have shown that the composites exhibit potent bioactivities and superior stability under physiological conditions and could promote osseointegration through regulating osteoblasts. More importantly, sustained biomechanical stability is attained immediately post-implantation and maintained long-term. In a rabbit model of large segmental femoral defects, osseous tissue exhibits longitudinal ingrowth along the composites, achieving bony bridging at both proximal and distal junctions with progressive remodeling. This culminates in a functionally stable bone-implant construct capable of enduring physiological loads. The current work not only develops a promising option for repairing critical-size load-bearing bone defects but also provides an idea and experimental basis for designing other functional bone biomaterials for large segmental bone defect applications.