Germanium-doped calcium phosphate ceramics in combination with mesenchymal stem cells derived from the neural crest, obtained from rabbit vibrissae: an experimental model of rabbit jaw regeneration

BACKGROUND: Jaw bone regeneration remains a clinical challenge in maxillofacial surgery. Bioactive ceramics and neural crest-derived multipotent mesenchymal stem cells (NC-MSCs) show regenerative potential, but their combined effect in repairing jaw defects has not been fully investigated. To our knowledge, no previous studies have evaluated germanium-doped biphasic calcium phosphate ceramics combined with NC-MSCs from vibrissae in a critical-size mandibular defect model. This study aimed to evaluate biphasic calcium phosphate ceramics doped with 1% germanium (BCPdGe 1%) alone versus BCPdGe 1% combined with NC-MSCs on rabbit mandibular defect regeneration and NC-MSC viability from rabbit vibrissae. METHODS: NC-MSC properties on modified ceramics were assessed in vitro using microscopic, cytochemical, and colorimetric analyses. Nine ceramic samples with different Ge and SiO2 concentrations and NC-MSCs from rabbit vibrissae were tested. The BCPdGe 1% group without stem cells was previously evaluated in the same rabbit mandibular defect model and used as a reference control following ethical 3R principles. In vivo, 30 rabbits with critical-size mandibular defects (7 mm) were assigned to BCPdGe 1% (n= 15) or BCPdGe 1%+NC-MSCs (n= 15). Bone regeneration was analyzed histologically, and data were processed in EZR (p< 0.05). RESULTS: NC-MSCs showed the highest viability with samples no. 3 (pure hydroxyapatite doped with 1.5% germanium), no. 5 (BCPdGe 1%), and no. 7 (biphasic calcium phosphate ceramics doped with SiO2). In vivo, BCPdGe 1% alone achieved significantly better bone regeneration than BCPdGe 1% combined with NC-MSCs. CONCLUSION: Implanted NC-MSCs are highly sensitive to local biological conditions and mechanical stress, highlighting the need for further research on stem cell sources and cultivation methods.