Sillmann Yannick M, Eber Pascal, Orbeta Elizabeth, Wilde Frank, Gross Andrew J, Guastaldi Fernando P S
Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Department of Oral and Plastic Maxillofacial Surgery, University Hospital Ulm, 89081 Ulm, Germany.
J Clin Med. 2025 Apr 15;14(8):2717. doi: 10.3390/jcm14082717.
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. 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. 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. 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.
创伤或肿瘤切除术后的下颌骨重建对于恢复功能和美观至关重要。虽然自体骨移植仍然是金标准，但它存在供区并发症和移植物可用性等挑战。骨组织工程（BTE）提供了一种创新的替代方法，将支架、成骨细胞和生物活性因子整合在一起以再生功能性骨。本系统评价评估了用于下颌骨重建的BTE策略，重点关注大型动物模型中的临界尺寸缺损及其临床应用的转化潜力。按照PRISMA指南进行了系统评价。符合条件的研究涉及大型动物模型和用至少两种BTE成分（支架、成骨细胞或生长因子）治疗的临界尺寸下颌骨缺损。使用ARRIVE指南和SYRCLE工具进行质量和偏倚评估。在筛选的6088项研究中，27项符合纳入标准，重点关注猪、羊和狗等大型动物模型中的临界尺寸下颌骨缺损。常见的支架包括β-磷酸三钙（β-TCP）、聚乳酸-乙醇酸共聚物（PLGA）和聚己内酯（PCL），它们经常与骨髓来源的间充质干细胞（BMSC）以及重组人骨形态发生蛋白-2（rhBMP-2）等生长因子联合使用。临床前结果显示了有效的骨再生、血管化和生物力学恢复。包括体内生物反应器和3D打印支架在内的先进策略进一步增强了再生。然而，观察到了诸如支架降解不完全、构建体内的缺氧条件以及生长因子疗效和剂量优化的变异性等挑战，强调需要进一步改进以确保一致的结果。BTE在下颌骨重建中显示出前景，在临界尺寸缺损的临床前模型中实现了骨再生和功能恢复。然而，诸如支架优化、血管化增强和方案标准化等挑战需要进一步研究以促进临床转化。这些发现强调了进行改进以实现临床使用中一致、可扩展结果的必要性。
