The clinical effectiveness and safety of using epidermal growth factor, fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing: a systematic review and meta-analysis

Background: Promoting wound healing is crucial to restore the vital barrier function of injured skin. Growth factor products including epidermal growth factor (EGF), fibroblast growth factor (FGF) and granulocyte-macrophage colony stimulating factor (GM-CSF) have been used for decades although no systematic evaluation exists regarding their effectiveness and safety issues in treating acute skin wounds. This has resulted in a lack of guidelines and standards for proper application regimes. Therefore, this systematic review and meta-analysis was performed to critically evaluate the effectiveness and safety of these growth factors on skin acute wounds and provide guidelines for application regimes. Methods: We searched PubMed/Medline (1980-2020), Cochrane Library (1980-2020), Cochrane CENTRAL (from establishment to 2020), Clinical Trials.gov (from establishment to 2020), Chinese Journal Full-text Database (CNKI, 1994-2020), China Biology Medicine disc (CBM, 1978-2019), Chinese Scientific Journal Database (VIP, 1989-2020) and Wanfang Database (WFDATA, 1980-2019). Randomized controlled trials (RCTs), quasi-RCTs and controlled clinical trials treating patients with acute skin wounds from various causes and with those available growth factors were included. Results: A total of 7573 papers were identified through database searching; 229 papers including 281 studies were kept after final screening. Administering growth factors significantly shortened the healing time of acute skin wounds, including superficial burn injuries [mean difference (MD) = -3.02; 95% confidence interval (CI):-3.31 similar to-2.74; p < 0.00001], deep burn injuries (MD = -5.63; 95% CI:-7.10 similar to-4.17; p < 0.00001), traumata and surgical wounds (MD = -4.50; 95% CI:-5.55 similar to-3.44; p < 0.00001). Growth factors increased the healing rate of acute skin wounds and decreased scar scores. The incidence of adverse reactions was lower in the growth factor treatment group than in the non-growth factor group. Conclusions: The studied growth factors not only are effective and safe for managing acute skin wounds, but also accelerate their healing with no severe adverse reactions.