Craniofacial Fracture and Secretome: A Systematic Review

Background: Restoring normal morphology and function after craniofacial fractures remains a clinical challenge. Tissue engineering, particularly through cell-free approaches using secretome (soluble proteins and extracellular vesicles), has emerged as a promising strategy for enhancing bone regeneration. This study aims to evaluate the effectiveness of secretome therapy for craniofacial bone regeneration in animal and human models. Methods: This review was conducted in August 2024 using Google Scholar, The Cochrane Library, and PubMed. Inclusion criteria encompassed methodological studies (in vitro, in vivo, or clinical) with full-text availability. Studies on noncraniofacial fractures were excluded. The Cochrane risk of bias 2.0 checklist assessed risk of bias. Results: Of 20 included articles, 4 involved human studies (48 participants) and 16 used animal models: dogs (1 study, 4 dogs), rabbits (2 studies, 34 rabbits), and rats (13 studies, 281 rats). Secretome boosted levels of bone-healing proteins, including vascular endothelial growth factor, insulin-like growth factor, osteocalcin, transforming growth factor-beta 1, proliferating cell nuclear antigen, angiopoietin-1, angiopoietin-2, bone morphogenetic protein 2, matrix metalloproteinase 8, matrix metalloproteinase 13, integrin-binding sialoprotein, Runt-related transcription factor 2, and intercellular adhesion molecule 1. X rays, computed tomography, and histological analyses indicated that secretome therapy expedited bone healing. Conclusions: Secretome therapy enhances craniofacial bone healing by promoting the production of key cytokines and facilitating repair over large areas. Further research with larger sample sizes and reduced risk of bias is needed to strengthen these findings.