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Craniofacial Fracture and Secretome: A Systematic Review

Oley MH, Oley MC, Suoth SC, Yong H, Faruk M, Sukarno V, Gunawan DF

Plastic and reconstructive surgery. Global open, 2026

48 participants

Abstract

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…

How strong is the evidence?

Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 48 participants or records.

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