The role of bioactive molecules in enhancing bone healing in oral and maxillofacial surgery: a review of current approaches and future directions

Bone regeneration in oral and maxillofacial surgery (OMFS) remains challenging, particularly in procedures such as alveolar ridge preservation, sinus floor augmentation, mandibular reconstruction, and peri implant bone regeneration. Bioactive molecules have emerged as promising therapeutic agents that enhance osteogenesis, angiogenesis, and tissue remodeling through modulation of key cellular signaling pathways.

A structured literature review was conducted using PubMed, Scopus, and Web of Science databases. The search primarily focused on studies published between 2020 and 2025 to capture recent advances, while incorporating foundational studies to support key biological mechanisms. Inclusion criteria comprised peer reviewed in in vitro, in vivo, and clinical studies investigating bioactive molecules and scaffold based bone regeneration strategies in OMFS.

Bioactive molecules including icariin, bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and dental pulp stem cell (DPSC) derived secretomes significantly enhance osteogenic differentiation, extracellular matrix mineralization, and angiogenesis. These effects are mediated through major signaling pathways such as BMP/Smad, MAPK/ERK, PI3K/Akt, and HIF-1α pathways. Integration with biomaterial scaffolds enables controlled spatiotemporal release, improving regenerative outcomes. However, translational challenges remain, including dose-dependent adverse effects (particularly with BMPs), suboptimal release kinetics, and limitations of current experimental models in replicating mandibular biomechanics.

Bioactive molecule-based therapies represent a promising approach for enhancing bone regeneration in OMFS. Future advancements in nanotechnology-based delivery systems, three-dimensional bioprinting, and personalized regenerative strategies are essential to bridge the gap between experimental success and clinical application.