Expression of Fas, Fas Ligand, bcl-2 in Fetal Wound Healing of Rats

Cutaneous wound healing in adult humans and higher vertebrate animals results in scar formation. In contrast, both human and animal fetuses at early gestational ages exhibit skin wound healing without scarring. A recent study has suggested that apoptosis occurs and plays an important role in achieving a decrease in cellularity during skin wound healing. The purpose of this study is to reveal the hypothesis the apoptosis may decreases the inflammatory infiltrates in fetal skin wound healing and may affect the fetal scarless wound healing. Open full-thickness incisional skin wounds were created on fetal rats at gestational ages 16 days(term= 21days). Wound were harvested at 24 hour(n=15), 72 hour(n=15), 120 hour(n=15). Adult skin wound was harvested at 24 hour(n=15), 72 hour(n=15), 120 hour(n =15). The wounds were fixed and stained with hematoxylin and eosin, TUNEL stain, immunohistochemical stain for Fas, Fas ligand, bcl-2. Fetal wounds was healed without scar formation and with regeneration of normal dermal and epidermal appendage architecture. Immunohistochemical staining for Fas, Fas ligand shows sparse positive cells in squamous epithelium of the both adult and fetus, there are no difference of expression between two groups. Immunohistochemical stainings for bcl-2 shows no positive cells in both adult and fetus. The apoptotic index of adult is 0.65+/-0.32 and fetus is 0.56 +/-0.37(p=0.464), there is no significant difference stastically between two groups. These data indicate that apoptosis is not likely to be related to decreased infiltration of inflammatory cells that is main factor of scarless fetal wound healing.

The fetal wound healing: a review

Fetal wound healing has drawn the attention of many researchers from diverse background and specialties. Fetal wound healing is unique and differs from postnatal healing in that fetal skin wounds heal rapidly without scar formation. If the mechanism underlying such phenomenon can be elucidated, it will be serve as a significant milestone in the study of wound healing. Furthermore, the implications for therapeutic applications in wound management and in diseases where scarring is the basic pathogenetic mechanism would be immense. Rather than to list the results and conflicting data of numerous studies, this article hopes to provide a general overview of the recent developments.

Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin

Wounds on fetal skin can be repaired without leaving scars until the second trimester, but after this period, skin wounds leave scars as in adults. It's known that certain growth factors such as TGF-beta, and bFGF are present at a very low levels during wound repair in fetal skin. These low levels of growth factors minimize inflammatory response and fibroblast proliferation at the wound site, which in turn inhibit collagen synthesis, and thus, allows scarless wound healing. Recently bone morphogenetic proteins (BMPs), one of the TGF-beta superfamily members, have been studied in the wound healing process. According to several studies, BMPs are related to the differentiation and growth of epithelial and mesenchymal cells, but the precise functions of BMPs and of BMP receptors on skin wound healing have not been elucidated. In this study, we investigated the expression pattern of BMP receptors in fetal skin during the second trimester and in adult skin by immunohistochemical staining and RT-PCR. BMP receptors were detected on the suprabasal epithelial cells and in the hair follicles in adult skin, but were not defected in the fetal skin except for the hair follicles. This was confirmed by confirming mRNA levels of BMP receptors by RT-PCR in both adult and fetal skins. In conclusion, BMPs and BMP receptors seem to be related to fetal and adult wound healing, and low levels of BMPs and BMP receptors during the second trimester seem to contribute to scarless wound healing in the fetus, as is TGF-beta during the second trimester.

A study on the extracellular matrix in the artificially created cleft lip wound healing of rabbit fetuses / 대한치과교정학회지

Adult wound healing is accompanied with inflammation and eventual scar formation, whereas fetal wounds heal rapidly by mesenchymal proliferation without significant inflammatory cell participation and with minimal or no scar formation. The cellular mechanisms underlying these differing forms of wound healing are unknown but the extracellular matrix, through its effects on cell function, may play a key role. Therefore the purpose of this study is to investigate the spatial and temporal deposition of several component of extracellular matrix, which are known to be involved with scar formation, in the artificially created cleft lip wound healing of fetuses. The author had undergone hysterotomy and created cleft lip-like defects on fetuses of New Zealand White Rabbit in mid-third trimester(24 days). Fetuses were divided into the repaired group, the unrepaired group and the sham-operated control group. At 1, 2, 3, 5, 7 days after procedure, fetuses were obtained by Caeserean section. After documenting the viability of fetuses, they were photographed to compare size and facial morphology and sectioned for histological examination by H & E stain and spatial and temporal deposition of collagen type I. III, IV, V and fibionectin, laminin by immunohistochemical method. The findings are summarized as follows: 1. There were lack of inflammation in the repaired and the unrepaired group during experimental periods. 2. The reepithelialization of the unrepaired group was slower than that of the repaired group. 3. Collagen I, III, V were found from post-op. third day. There were no difference of distribution in the control, the repaired and the unrepaired group. Collagen types I, III, V were present in all groups with restoration of the normal collagen pattern in the fetus. This implies that lack of scarring in fetal wounds is due to the difference of collagen organization pattern within wound and not simply lack of collagen formation. 4. Collagen IV was slightly increased at post-op. third day and decreased after post-op, fifth day. Eventually there were no differences in the control, the repaired and the unrepaired group. Laminin was found at post-op. fifth day and maintained staining density until post-op. seventh day. There were no differences in the control, the repaired and the unrepaired group. According to staining of laminin and collagen type IV in epithelial basement membrane, formation of epithelial basement membrane was not completed until reepithelialization was finished. 5. According to staining of laminin and collagen type IV, there were no increase of neovascularity in the repaired and the unrepaired group. 6. Fbbronectin was increased until post-op. third day at fibrin clot, wound base and margin and decreased after post-op. fifth day. Eventually, there were no differences in the control, the repaired and the unrepaired group, So it implies fibronectin plays a role as provisional matrix for fetal wound healing

A study on the distribution of several growth factors in the artificially created cleft lip wound healing of rabbit fetuses / 대한치과교정학회지

Recently several growth factors such as TGF-beta1, TGF-beta2, PDGF, bFGF are known to play an important role in scar formation following adult tissue injury. But there is little known about the role of growth factors tissue healing without scar formation. Therefore the pupose of this study is to investigate the distribution of growth factors which are involved with scar formation in the artificially created lip wound healing of fetuses. The author had undergone hysterotomy and created cleft lip-like defects on fetuses of New Zealand White Rabbit in mid-third trimester (24 days). Fetuses were divided into 3 groups (the repired group, the unrepaired group and the sham-operated control group). At 1, 2, 3, 5, 7 days agter procedure, the repaired, the unrepaired and the control groups were obtained by Caeserean section. After documenting the viability of fetuses, fetuses were photographed to compare size and facial morphology and sectioned for histological examination by H & E stain and spatial and temporal deposition of TGF-beta1, TGF-beta2, PDGF, bFGF by immunohistochemical method. The findings are summarized as follows. 1. There were lack of inflammation and scar formation and nevascularity in the repaired and the unrepaired group during experimental periods. 2. The reepothelialization of the unrepaired group was slower than that of repaired group. 3. There wereon differences of distribution of bFGF in the control, the repaired and the unrenaired group. 4. PDGF was increased at post-op, first and second day and decreased agter post-op, third day. Eventully, there were no differences in the control, the repaired and the unrepaired group. 5. TGF-beta1 and TGF-beta2 were slightly increased at post-op, first and second day decreased after post-op, thied day. Eventually there were no differences in the control, the repaired and the unrepaired group. And TGF-beta2 is more densely stained than TGF-beta1.