Human umbilical cord-derived mesenchymal stem cells/Bio-Oss granules composite prevents medication-related osteonecrosis of the jaw in a rat model

Objective To evaluate the preventive efficacy of human umbilical cord-derived mesenchymal stem cells (hucMSCs)/Bio-Oss granules composite in a rat model of medication-related osteonecrosis of the jaw (MRONJ). Materials and methods Twenty-four rats were randomly allocated into a negative control group, a model control group, a Bio-Oss granules group, and a composite group (n = 6). All groups except the negative control group received intraperitoneal injections of zoledronic acid (0.1 mg/kg) 3 times per week for 12 weeks to induce MRONJ-like lesions. After 4 weeks of drug administration, standardized bone defects were prepared at the mandibular molar extraction sites. In the negative control and model control groups, the defects were left unfilled. In the Bio-Oss granules and composite groups, the defects were filled with Bio-Oss granules or hucMSCs/Bio-Oss granules composite, respectively. All rats were euthanized 8 weeks after surgery. Macroscopic observation, micro-CT evaluation, and histological analysis were conducted to assess bone exposure rate, bone volume fraction (BV/TV), bone mineral density (BMD), and the percentage of empty osteocyte lacunae. Results The bone exposure rate was 0% in both the negative control and composite groups, compared with 83.33% and 66.67% in the model control and Bio-Oss granules groups, respectively. The composite group showed improved mucosal coverage, as well as significantly higher BV/TV and BMD and fewer empty osteocyte lacunae than the other bisphosphonate (BP)-treated groups ( P < 0.001). Conclusion Bio-Oss granules alone showed limited efficacy in preventing MRONJ. In contrast, the hucMSCs/Bio-Oss granules composite effectively promoted mucosal healing and bone regeneration, thereby preventing the development of MRONJ in BP-treated rats.