Regenerative and tissue engineering strategies for segmental mandibular reconstruction

Segmental mandibular reconstruction following major ablative surgery, tumor resection, trauma, or osteonecrosis remains a formidable clinical challenge due to the region's complex anatomical, functional, and aesthetic demands. Although autologous vascularized bone grafts, such as the fibula free flap, remain the gold standard, they are limited by donor-site morbidity, restricted vertical height, and geometric incongruence. Bone tissue engineering offers a promising alternative by combining biomaterial scaffolds, osteogenic cells, and bioactive molecules to regenerate functional bone. Advances in scaffold design, particularly the use of nanocomposites, three-dimensional printing, and bioresorbable polymers, have enabled the fabrication of biomimetic constructs that promote vascularization and osseointegration. The integration of stem cells and the controlled release of growth factors, such as BMP-2 and VEGF, further enhance osteoinduction and bone regeneration. Recent translational studies demonstrate the feasibility of prevascularized and in situ-vascularized engineered bone constructs for the repair of large mandibular defects. However, clinical translation remains constrained by challenges in achieving consistent vascularization, functional innervation, mechanical integrity, and long-term functional integration. This review summarizes current advances in biomaterial design, bioreactor-based preconditioning, and vascularization strategies for tissue-engineered mandibular reconstruction. It also discusses emerging clinical and preclinical evidence and future directions toward scalable, patient-specific regenerative solutions. Continued interdisciplinary collaboration among tissue engineers,biomaterial scientists, surgeons, and regulatory stakeholders will be critical to translating these innovations into reliable clinical therapies.