Clinical evidence on bone tissue engineering for craniomaxillofacial reconstruction: a narrative review

Background and Objective: Bone defects in the craniomaxillofacial (CMF) region represent a significant clinical challenge due to their anatomical complexity and functional demands. Although autogenous bone grafts remain the clinical gold standard, their use is constrained by donor-site morbidity, limited availability, and variable outcomes. These limitations have driven the development of bone tissue engineering (BTE) strategies as alternative therapeutic approaches. The purpose of this article is to summarize the current clinical evidence supporting BTE strategies for CMF bone regeneration.

Methods: A structured literature search was conducted using Web of Science, PubMed and Scopus databases to identify studies published in English between 2005–2025. Clinical studies, including randomized controlled trials, case series and case reports were included if they evaluated BTE approaches using stromal cells (SCs), biomaterials as scaffolds, and/or growth factors. Relevant data were extracted and synthesized descriptively.

Key Content and Findings: Thirty-seven studies met the inclusion criteria and were analyzed with respect to cell sources, scaffold materials, use of growth factor, reconstructed sites, clinical outcomes, and complications. Autologous SCs, particularly bone marrow-derived populations, remain the most widely used and clinically validated cell source, while alternative adipose and oral-derived SCs show growing potential due to niche compatibility. β-tricalcium phosphate-based ceramics were the most frequently employed scaffolds, often combined with collagen, platelet-rich plasma, or other biomaterials to enhance biological performance. The majority of studies did not incorporate exogenous growth factors as bone morphogenetic proteins. Clinical outcomes were generally favorable for contained defects such as sinus augmentation and alveolar ridge reconstruction, whereas larger, non-contained defects highlighted the critical importance of vascularization and mechanical stability.

Conclusions: Despite encouraging results, challenges persist, especially in large or critical-sized defects, where insufficient vascularization, scaffold properties, and biological variability limit predictability. Advances in biomaterial design, vascularization strategies, and standardized clinical protocols are essential to enhance the translational success of BTE. Overall, current evidence supports BTE as a viable and safe alternative for selected CMF applications, while highlighting the need for larger, well-controlled clinical trials to optimize therapeutic outcomes.