Abstract: Objective: To construct and evaluate a novel tissue-engineered bone composed of murine stromal cell-derived factor 1(mSDF-1), simvastatin (SIM) and collagen scaffold （Bio-Oss^®）, serving as a cell-homing approach for bone formation. Methods:  In the study, 32 ICR mice were randomly divided into 4 groups，each group including 8 mice. The drug-loaded collagen scaffolds were implanted subcutaneously onto the cranium of each mouse according to the groups: (1) 1 ∶50 (volume ratio) dimethyl sulfoxide (DMSO) / phosphate-buffered saline(PBS) solution + collagen scaffold (blank control group); (2) 10^-3 mol/L SIM solution + collagen scaffold (SIM group); (3) 200 mg/L mSDF-1solution + collagen scaffold (mSDF-1 group); and (4) 10^-3 mol/L SIM +200 mg/L mSDF-1 solution + collagen scaffold (SIM + mSDF-1 group). One week after implantation, the mice were treated by injecting the same drug solution mentioned above around the scaffold once a day for two days. The specimens were harvested 6 weeks after implantation and the bone formation was evaluated by soft X-ray analysis, HE staining and immunohistochemical staining. Angiogenesis of each group was checked by calculation of vessels in each tissue section. Results: Six weeks after implantation, the collagen scaffolds were retrieved. The value of gray scale for the SIM+mSDF-1 group［（421 836.5±65 425.7）pixels］ was significantly higher than that of the blank control group［（153 345.6±45 222.2）pixels, P<0.01］, the SIM group ［（158 119.2±100 284.2）pixels, P<0.01］, and the mSDF-1 group［（255 529.5±152 142.4）pixels, P<0.05］; HE staining analysis revealed that significant bone formation was achieved in the SIM + mSDF-1 group; The immunohistochemical staining showed the existence of osteopontin and osteocalcin in the SIM + mSDF-1 group; There were more vessels in the SIM+mSDF-1 group［（46±8）vessels/mm²］ than in the blank control group ［(23±7) vessels/mm², P<0.01］, and the SIM group［(24±6) vessels/mm², P<0.01］. Conclusion: The novel tissue-engineered bone composed of mSDF-1, SIM and collagen scaffolds has the potential to form bone subcutaneously in vivo. It represents a novel method of in vivo bone regeneration without seed cell delivery.

Key words: Chemokine CXCL12, Simvastatin, Collagen, Osteogenesis