Mechanobiology of Distraction Osteogenesis in the Mandible: Investigating Cellular and Molecular Responses to Distraction Forces in a Nigerian Patient Cohort

Distraction osteogenesis (DO) exploits the biological capacity of bone to regenerate in response to controlled tensile forces, but the mechanobiological mechanisms governing this response, particularly in mandibular regenerate formation, are not fully elucidated in African populations who may differ in bone metabolism, healing genetics, and systemic disease burden. This translational PhD study investigates the cellular and molecular responses to mandibular distraction forces in a cohort of Nigerian patients undergoing DO for hemifacial microsomia, post-traumatic micrognathia, and noma-related jaw defects at JUTH Jos and UBTH Benin. Sequential tissue biopsies from the distraction gap were obtained during the activation phase (day 7 and day 14) and the consolidation phase (week 8). Histological, immunohistochemical, and gene expression analyses were performed to characterize osteoblast and osteoclast activity, vascular ingrowth, collagen fiber maturation, and expression of mechanosensitive genes including COX-2, RUNX2, VEGF, and BMP-2. Serum markers of bone turnover (P1NP, CTX-1, osteocalcin) were serially measured and correlated with regenerate quality on CT imaging. Results reveal peak mechanosensitive gene expression at day 14, with VEGF and BMP-2 upregulation preceding radiographically detectable mineralization. Patients with concurrent sickle cell trait demonstrated delayed regenerate mineralization and lower RUNX2 expression. The study provides original mechanobiological evidence from a Nigerian patient cohort, identifies sickle cell trait as a modulator of distraction osteogenesis biology, and informs clinical protocols for DO device activation rates in Nigerian patients. Keywords: distraction osteogenesis, mechanobiology, mandible, molecular response, Nigeria.