The formation and proliferation of scar after wound healing has been a difficult problem in burn treatment, and there is no effective method for scar prevention and control, while the mechanism of scar formation has been studied more in basic research. It has been reported that some scholars have studied the characteristics of fibroblasts in skin wounds and confirmed that fibroblasts exhibit strong proliferative ability during wound healing, which is believed to be the cause of scar formation. It has also been shown that collagen is secreted and deposited in large quantities during the healing process, and type I collagen fibers are predominant in adults, thus suggesting that the abnormal secretion of collagen is the cause of scarring. The expression of various growth factors and their receptors during the healing process and in the scar was studied, and it was observed that the expression of transforming growth factor β (TGF-β) and basic fibroblast growth factor (bFGF) and their receptors were very different from those in normal skin. It is believed that growth factors play an important role in the development of keloid scars. The relationship between scar healing process and inflammatory response has also been investigated, and it was observed that the degree of scar formation was positively correlated with the strength of inflammatory response during scar healing process. Some scholars have also studied the relationship between sex hormones and scar formation, and observed that estrogen can promote wound healing, while the levels of progesterone and androgen in hyperplastic scars are higher than normal, suggesting that scar formation is related to sex hormones. It has also been observed that the degree of scarring varies in different areas, such as the midline of the chest and the upper back, where the skin tension is higher, so it is believed that the local biological stress of the skin is also an important reason for scarring. It is believed that different species and races are also closely related to scar production, etc. The above studies have greatly improved the understanding of the mechanism of scar production, but it seems that there is still a long way to go before the mechanism of scar production is fully understood and the scar is completely prevented and treated clinically. What are the root causes of scarring and where is the next direction of research? It is worth considering.
In 1971, Burrington et al. observed no scar formation after fetal skin trauma in mid-pregnancy and proposed the concept of “scarless healing”, which led to the study of the mechanism of scarless healing, hoping to replicate this process in adults and thus avoid scar formation. The first phase of research focused on the external environment of the fetus, such as warm, sterile amniotic fluid and low partial pressure of oxygen, but later studies confirmed that these were not the underlying causes of fetal scarless healing. The latter research has focused on the intrinsic factors of fetal skin healing, such as the characteristics of fetal fibroblasts themselves and the components of the extracellular matrix. (2) The phenotype of fetal trauma fibroblasts is different from that of adults and has a strong wandering nature; (3) Fetal trauma contains a high concentration of hyaluronic acid and can be maintained for a longer period of time, which makes the extracellular matrix more mobile and flexible, which is conducive to the proliferation and wandering of fibroblasts. (4) The percentage of type III/I collagen in fetal trauma is higher than that in adults, and the collagen fibers are arranged in a normal reticular pattern; (5) Growth factors such as TGF and bFGF are lowly expressed in fetal trauma healing process. What is the main reason for the “scarless healing” of fetal wounds?
Lorenz et al. observed that fetal wounds in late gestation can develop a transition period between adult-like scar tissue healing and early scarless healing, and called this “transitional scar”, which is characterized by a normal reticular arrangement of dermal collagen fibers in the healing wound but the absence of skin attachments. Why do “transitional scars” occur? Is it related to the developmental state of the fetus during its transition to adulthood?
Stelnicki et al. showed that the ability of mammalian fetuses to repair large skin defects perfectly, in a regenerative fashion, may be related to their paradigm genes, such as the homozygous heterozygous frame gene. Homozygous heterozygous box genes are the major developmental regulatory genes in animals, building on all genetic levels and regulating all aspects of morphogenesis and cell differentiation. The homologous alloform cassette is a common fragment within all homologous alloform frame genes, 183 bp in size, first found in Drosophila, and later shown to be present in all postnatal animals from sponges to vertebrates, as well as in plants and fungi, and is highly conserved during evolution. The homodomain cassette encodes a 60 amino acid homeodomain, which acts on specific sequences of DNA to regulate larger homodomain proteins, i.e. transcriptional regulators, which can activate or repress the expression of target genes. The expression of homologous heterodomain genes varies during different stages of development. During normal skin development, cells from ectoderm, mesoderm and endoderm work together in a precise temporal and spatial sequence to form a complex three-dimensional meshwork, all of which is regulated by homologous heteromeric frames. The expression of MSX21, MSX22 and MOX21 in human fetal skin and adult skin was found to differ.
The mechanism of “scarless healing”, as a special phenomenon in fetal development, must be closely related to developmental biology. This result suggests that fetuses and adults are at different developmental stages and that many differences in their developmental biology may be the underlying cause of the different healing outcomes. A comparative study of the developmental biology of fetal, adult, and neonatal skin wound healing, to identify the differences, and then apply the appropriate intervention factors to observe the changes in wound healing, may be the best way to elucidate the mechanisms of “scarless healing”, “transitional scarring”, and scar production in fetuses. It may be a better direction to elucidate the mechanisms of “scarless healing”, “transitional scar” and scar production in fetuses.