Bone defects stemming from trauma, infection, osteoporosis, tumor resection, and congenital or metabolic bone diseases often demand effective strategies for repair. Current bone graft options, such as autologous or allogeneic bone, face limitations related to donor morbidity, immune rejection, and poor osseointegration. Bone tissue engineering, which integrates biocompatibility, osteogenic capacity, and angiogenic potential, therefore offers a promising approach for bone defect repair. This study evaluated the therapeutic potential of a novel composite scaffold, the TGP-377 nanoparticles-loaded HAMA hydrogel-infused PLGA/β-TCP (THPT) scaffold, in supporting early bone repair and angiogenesis-related responses. The scaffold was designed to provide sustained local release of TGP-377 and to support concurrent osteogenic and angiogenesis-related responses. , In vitro, TGP-377 exhibited pronounced osteogenic and angiogenic effects, boosting MC3T3-E1 cell proliferation and osteogenic differentiation, alongside HUVEC proliferation and migration. In a rabbit femoral defect model, THPT increased mineralized tissue-related micro-CT indices and osteogenic and angiogenesis-related marker expression at 4 weeks. Moreover, the scaffold demonstrated favorable biocompatibility, with no pathological changes observed in major organs. These findings support further investigation of THPT as a local bioactive scaffold for early bone-defect repair.