Background: Most materials used clinically for filling severe bone defects lack the ability to induce bone regeneration or low bone conversion rate, therefore, their therapeutic effects are limited. Human umbilical cord mesenchymal stem cells (HUC-MSCs) have good osteoinduction. The mechanism of heterogeneous bone collagen matrix combined with HUC-MSCs in repairing bone defects of alveolar process cleft is still unclear.Methods: Here, a rabbit alveolar process cleft model was established to evaluate the repair effect and molecular mechanism of bone collagen matrix and its combination with HUC-MSCs on critical-sized bone defects in the alveolar process. We randomly divided 48 young Japanese white rabbits (JWRs) into normal, control, material and MSCs groups. The alveolar process cleft model was established by removing the bone of equal volume at the left maxillary. Bone collagen matrix combined with HUC-MSCs that were then implanted in the defect area. X-ray analysis and blood analysis were analyzed 3 months after surgery. Skull tissues were collected for micro-focus computerized tomography (micro-CT) analysis and histochemical staining. The above experiment was repeated 6 months after surgery.Results: the main findingsResults: It was found that bone collagen matrix and HUC-MSCs showed good biocompatibility. Heterogeneous bone collagen matrix combined with HUC-MSCs significantly enhanced osteoinduction and osteoconduction. Conclusions: This experiment provides a new method for repairing alveolar process cleft.Trial registration: Not applicable.