Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity and graft availability. Bone tissue engineering (BTE) offers an innovative alternative, integrating scaffolds, osteogenic cells, and bioactive factors to regenerate functional bone. This systematic review evaluates BTE strategies for mandibular reconstruction, focusing on critical-sized defects in large animal models and their translational potential for clinical applications. Methods: A systematic review was performed following PRISMA guidelines. Eligible studies involved large animal models and critical-sized mandibular defects treated with at least two BTE components (scaffold, osteogenic cells, or growth factors). Quality and bias assessments were conducted using ARRIVE guidelines and SYRCLE tools. Results: Of the 6088 studies screened, 27 met the inclusion criteria, focusing on critical-sized mandibular defects in large animal models such as pigs, sheep, and dogs. Common scaffolds included β-tricalcium phosphate (β-TCP), poly-lactic-co-glycolic acid (PLGA), and polycaprolactone (PCL), frequently combined with bone marrow-derived mesenchymal stem cells (BMSCs) and growth factors like recombinant human bone morphogenetic protein-2 (rhBMP-2). Preclinical outcomes demonstrated effective bone regeneration, vascularization, and biomechanical restoration. Advanced strategies, including in vivo bioreactors and 3D-printed scaffolds, further enhanced regeneration. However, challenges such as incomplete scaffold degradation, hypoxic conditions within constructs, and variability in growth factor efficacy and dose optimization were observed, emphasizing the need for further refinement to ensure consistent outcomes. Conclusions: BTE shows promise in mandibular reconstruction, achieving bone regeneration and functional restoration in preclinical models of critical-sized defects. However, challenges such as scaffold optimization, vascularization enhancement, and protocol standardization require further investigation to facilitate clinical translation. These findings emphasize the need for refinement to achieve consistent, scalable outcomes for clinical use.

Artificial intelligence (AI), specifically machine learning (ML), is increasingly applied in decision-making for dental diagnosis, prognosis, and treatment. However, the methodological completeness of published models has not been rigorously assessed. We performed a scoping review of PubMed-indexed articles (English, 1 January 2018‒31 December 2023) that used ML in any dental specialty. Each study was evaluated with the TRIPOD + AI rubric for key reporting elements such as data preprocessing, model validation, and clinical performance. Out of 1,506 identified studies, 280 met the inclusion criteria. Oral and maxillofacial radiology (27.5%), oral and maxillofacial surgery (15.0%), and general dentistry (14.3%) were the most represented specialties. Sixty-four studies (22.9%) lacked comparison with a clinical reference standard or existing model performing the same task. Most models focused on classification (59.6%), whereas generative applications were relatively rare (1.4%). Key gaps included limited assessment of model bias, poor outlier reporting, scarce calibration evaluation, low reproducibility, and restricted data access. ML could transform dental care, but robust calibration assessment and equity evaluation are critical for real-world adoption. Future research should prioritize error explainability, outlier reporting, reproducibility, fairness, and prospective validation.

Critical-sized bone defects (CSBDs) are injuries that exceed the body’s natural capacity for repair and require external intervention. These defects are particularly challenging in the mandible, often resulting from trauma, tumor resection, or implant-related complications. Effective treatment involves scaffold designs that support vascularization, bone formation, and sufficient mechanical strength. This systematic review aims to assess whether ceramic-based scaffold properties, including porosity, pore size, and macroscopic characteristics, improve vascularization, bone formation, and the mechanical properties in the treatment of CSBDs in large animal models. A search of databases (PubMed, Embase, and Web of Science) identified 11 in vivo studies involving CSBDs (>2 cm), ceramic scaffolds, and histological analysis. Findings indicate that scaffolds with porosity exceeding 50% yield optimal outcomes by striking a balance between cell infiltration and mechanical stability. Pore sizes ranging from 300 μm to 700 μm are ideal for vascularization and bone ingrowth. Three-dimensional (3D) printing shows promise in creating scaffolds with precise and reproducible features. However, the studies varied significantly in their methodologies and outcomes, with no consensus on the optimal scaffold properties for mandibular CSBDs. Scaffold porosity and pore size play key roles in promoting vascularization and bone regeneration. Various animal models reinforce this finding, suggesting that scaffold architecture is crucial for biological integration and functional outcomes. This review highlights the importance of standardized research protocols and clear design criteria in enhancing the success of bone regeneration. Future research should investigate emerging biomaterials and new scaffold technologies to overcome current limitations in clinical applications.

Scaffold architecture is a key determinant of cell behavior and tissue regeneration in bone tissue engineering, yet the influence of pore size under dynamic culture conditions remains incompletely understood. This study aimed to evaluate the effects of scaffold pore size on osteogenic differentiation of porcine bone marrow-derived mesenchymal stem cells (pBMSCs) cultured in a rotational oxygen-permeable bioreactor system (ROBS). Three-dimensionally (3D) printed beta-tricalcium phosphate (β-TCP) scaffolds with pore sizes of 500 µm and 1000 µm were seeded with pBMSC and cultured for 7 and 14 days under dynamic perfusion conditions. Gene expression analysis revealed significantly higher levels of osteogenic markers (Runx2, BMP-2, ALP, Osx, Col1A1) in the 1000 µm group, particularly at the early time point, with the later-stage marker Osteocalcin (Ocl) rising faster and higher in the 1000 µm group, after a lower expression at 7 days. ALP activity assays corroborated these findings. Despite having lower mechanical strength, the 1000 µm scaffolds supported a homogeneous cell distribution and high viability across all regions. These results suggest that larger pore sizes enhance early osteogenic commitment by improving nutrient transport and fluid flow in dynamic culture. These findings also support the use of larger-pore scaffolds in bioreactor-based preconditioning strategies and underscore the clinical importance of promoting early osteogenic differentiation to reduce in vitro culture time, an essential consideration for the timely preparation of implantable grafts in bone tissue engineering.