The fast osteogenesis of the large alveolar fossa and the maintenance of the height of the alveolar ridge after tooth extraction have always been a clinical challenge. Therefore, this work describes the creation of innovative silk fibroin/collagen/hydroxyapatite (SCH) biological scaffolds by 3D printing technology, which are loaded with recombinant human erythropoietin (rh-EPO) for the reconstruction of bone defects. Low-temperature 3D printing can maintain the biological activity of silk fibroin and collagen. The SCH scaffolds showed the ideal water absorption and porosity, being a sustained-release carrier of rh-EPO. The optimized scaffolds had ideal mechanical properties in vitro, and MC3T3-E1 cells could easily adhere and proliferate on it. In vivo experiments in rabbits demonstrated that the composite scaffolds gradually degraded and promoted the accumulation and proliferation of osteoblasts and the formation of collagen fibers, significantly promoting the reconstruction of mandibular defects. In this study, a novel composite biological scaffold was prepared using 3D printing technology, and the scaffold was innovatively combined with the multifunctional growth factor rh-EPO. This provides a new optimized composite material for the reconstruction of irregular mandible defects, and this biomaterial is promising for clinical reconstruction of alveolar bone defects.