Dermatologic surgery Strategies for prevention of scars: what can we learn from fetal skin? Mohammad Reza Namazi 1 , MD, Mohammad Kazem Fallahzadeh 2 , MD, and Robert A. Schwartz 3 , MD, MPH 1 Stem Cell and Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, 2 Dermatology Department, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran, and 3 Department of Dermatology and Pathology, New Jersey Medical School, Newark, NJ, USA Correspondence Dr. Mohammad Kazem Fallahzadeh, MD Dermatology Department Faghihi Hospital Shiraz Iran E-mail: kazem.fa@gmail.com Funding sources: None. Conflict of interest: None. Abstract Fetal wound healing occurs rapidly and without scar formation early in gestation. Studying the mechanisms of scarless repair can lead to novel scar-preventive approaches. In fetal wounds, collagen is deposited early and is fine and reticular with less cross-linking. Several important differences of fetal vs. postgestational wound-healing response have been determined, such as the presence of less inflammation, higher hyaluronic acid concentration and a greater ratio of collagen type III to type I. Compared with typical wounds, there are also altered ratios of signaling molecules, such as higher ratios of transforming growth factor (TGF)-b3 to TGF-b1 and -b2, and matrix metallo- proteinases to tissue inhibitors of metalloproteinases. Furthermore, fetal fibroblasts do not exhibit TGF-b1-induced collagen production compared with their mature counterparts. Patterning genes (homeobox genes) involved in organogenesis are more active in the fetal period and are believed to be the ‘‘first domino’’ in the fetal cutaneous wound repair regulatory cascade. The recommended scar-preventive agents, such as Scarguard MD â , silicone gel and sheet, Seprafilm â Bioresorbable Membrane, topical hyaluro- nan, onion extract, oral tamoxifen and 585-nm pulsed dye laser are reviewed in this study. Despite the lack of supporting evidence, there is a widespread false presumption that the acceleration of healing with the widely assumed scar-preventive commercial agents is associated with decreased scar formation. Humans are erroneously inclined to make a negative correlation between the healing rate and the degree of scar formation, while such a correlation does not exist in reality. Despite the importance of scar preven- tion, no FDA-approved therapy for this purpose is available in the 21st century, which reflects the important challenges, such as the presence of redundant pathways, that these approaches are facing. Introduction Scar formation is a major clinical problem resulting in adverse cosmesis, loss of function, especially if over joints, and hindrance of growth in children. Scars also have a dra- matic impact on the patient’s quality of life, and have been associated with anxiety, social avoidance, and depression. 1 Therefore, prevention of scar formation has long been important. Scar reduction is not only important to derma- tologists, but is also salient in many other conditions, such as adhesions and strictures resulting from surgical proce- dures in abdominal and pelvic cavities, spinal cord rup- tures, scarification of hand tendons after injury, corneal abrasions, glomerulonephritis, cirrhosis, human vascular restenosis lesions, myocardial infarction, systemic sclerosis, and diffuse fasciitis. The principles of anti-scarring therapy based on modulation of pro-scarring vs. anti-scarring fac- tors appear to be promising for all the above-mentioned conditions, indicating that studies in the skin could have a broader clinical application. Scarless healing Scar and fibrosis are the end result of surgical and non- surgical skin injury. Aggressive wound healing may have once offered an evolutionary advantage for survival at the expense of scar formation. Amazingly, fetal cutaneous wounds, especially in the first 6 months of gestation, heal without scar formation. 2 Many clinicians hope that understanding the remarkable reparative capabilities of 85 ª 2011 The International Society of Dermatology International Journal of Dermatology 2011, 50, 85–93