Orassi, VincenzoVincenzoOrassiRuf, PhilippPhilippRufSteffen, ClaudiusClaudiusSteffenDuda, GeorgGeorgDudaHeiland, MaxMaxHeilandRendenbach, CarstenCarstenRendenbachCheca Esteban, SaraSaraCheca Esteban2025-10-302025-10-302025-10-20Clinical Oral Investigations 29 (11): 518 (2025)https://hdl.handle.net/11420/58382Objectives: Recent advancements in mandibular reconstruction, including virtual surgical planning and patient-specific 3D-printed reconstruction plates, have improved surgical precision but have not yet fully optimized the mechanical environment for bone healing. This study aimed to investigate the level of mechanical signals that may promote bone regeneration in mandibular reconstruction with patient-specific plates. Materials and methods: A coupled finite‑element and agent‑based mechanobiological model for mandibular bone healing was developed to predict bone formation after mandibular reconstruction. A finite element model (FEM) of a monosegmental mandibular reconstruction with a patient-specific 3D-printed plate during unilateral clenching was coupled with a 3D agent-based model to simulate cellular activities at the osteotomy sites. Using an established mechano-regulation theory, tissue formation and resorption were simulated based on mechanical signals. The latter were systematically varied to identify thresholds matching clinical observations. Results: Increasing the ossification threshold from 0.15 MPa to 0.30 MPa improved agreement with clinical data, leading to 39% and 69% of bone formation in the anterior and posterior gaps, respectively, after 90 days. Conclusions: The model was able to predict levels of newly-formed bone as per clinical observations. Adaptation of the mechano-regulation theory to the mandibular environment suggested that mandibular bone regeneration might occur at a higher level of mechanical stress than in long bones. Clinical relevance: This study presented a computational framework that could, in the future, be incorporated into the clinical workflow during virtual surgical planning to support the mechanical optimization of patient-specific fixation devices and ultimately enhance the healing outcome.en1436-3771202511SpringerAgent-based modelBone regenerationFinite elementMechanobiologyPatient-specific platesVirtual surgical planTechnology::610: Medicine, HealthJournal Article10.1007/s00784-025-06586-wJournal Article