So far, studies on the mechanism of scar formation have mainly focused on cells, cytokines and extracellular matrix. Some studies have shown that fibroblast is one of the most important element in the process of scar formation, while epidermal and endothelial cells exert synergistic effects as well. Genetic factor can not be ignored in scar formation, either. Recently, studies have shown decisively the loss or damage of the three-dimensional structure of dermal tissue is the initiator of scar formation. Thus, the defect of epidermis template is proposed as a theory in order to explain the mechanism of scar formation. There are various techniques for scar treatment. The commonly accepted methods are physical therapy, pressure therapy, pharmaceutical therapy, radiotherapy, etc.
Cicatrix ; metabolism ; pathology ; therapy ; Dermis ; pathology ; Humans

Stasis dermatitis is an itchy, scaly, and hyperpigmented condition of the lower leg due to venous insufficiency. Hemosiderin and/or melanin have been considered responsible for the brown pigmentation. However, there are not sufficient histopathologic studies. In this retrospective study the hospital records and biopsy slides of 20 patients were reviewed to determine the pathogenetic mechanisms of brown pigmentation in stasis dermatitis. Fifteen were men (75%) and 5 were women (25%) with a mean age of 46.2+/-8.2 yr (18-76), mean age at onset of 43.4+/-18.0 yr (17-73), and a mean duration of the disease 2.8+/-2.5 yr (0.25-10). All patients had varicose vein and complained of pruritus. On histopathologic evaluation, two cases out of 20 (3 skin biopsy specimens from 25 samples) showed dermal melanocytes containing melanin, and incontinence of melanin pigment was observed in 5 cases, which indicates that melanin pigments from epidermis could contribute to cutaneous pigmentation in stasis dermatitis. However, the existence of dermal melanocytes in two cases cannot be explained because normally the dermis contains no melanocytes. Further studies concerning the role of iron or inflammatory cytokines on the development of dermal melanocytes should be conducted.
Adolescent ; Adult ; Aged ; Dermatitis/etiology/metabolism/*pathology ; Dermis/metabolism/pathology ; Female ; Humans ; Hyperpigmentation/etiology/metabolism/*pathology ; Leg Dermatoses/etiology/metabolism/pathology ; Male ; Melanins/metabolism ; Melanocytes/metabolism/*pathology ; Middle Aged ; Venous Insufficiency/complications

Objective: To explore the effect of deep dermal tissue dislocation injury on skin fibrosis in pig, in order to provide some theoretical basis for burn scar treatment. Methods: The experimental research method was applied. Six 2-month-old female Duroc pigs were taken. Fifteen operative areas on the right dorsum of pigs on which medium-thick skin grafts and deep dermal tissue slices were cut and re-implanted were included into dermal in situ reimplantation group, and fifteen operative areas on the left dorsum of pigs on which medium-thick skin grafts and deep dermal tissue slices were cut and the deep dermal tissue slice was placed under the fat layer were included into the dermal dislocation group. The hair growth in the operative areas on post-injury day (PID) 7, 14, and 21 and the cross-sectional structure on PID 14 were observed in the two groups. On PID 7, 14, and 21, the skin thickness (the distance from the epidermis to the upper edge of the fat), the dermal thickness (the distance from the lower edge of the epidermis to the upper edge of the fat, excluding the fibrotic tissue thickness between the dermis and the fat), and the fibrosis tissue thickness of the dermis-fat interface (from the lower edge of the deep dermis to the upper edge of the fat in dermal in situ reimplantation group and from the lower edge of the superficial dermis to the upper edge of the fat in dermal dislocation group) in the operative areas were measured and compared between the two groups; the fibrotic tissue thickness at the dermal cutting interface (from the lower edge of the superficial dermis to the upper edge of the deep dermis) in the operative areas in dermal in situ reimplantation group was measured and compared with the fibrotic tissue thickness at the dermal-fat interface. Sirius red staining was performed to observe and compare the type Ⅰ and Ⅲ collagen content in the dermal-fat interface in the operative areas between the 2 groups and between the dermal cutting interface and dermal-fat interface in the operative areas in dermal in situ reimplantation group. Immunohistochemical staining was performed to observe the positive expressions of proliferating cell nuclear antigen (PCNA), transforming growth factor β₁ (TGF-β₁), fibroblast growth factor 2 (FGF-2), and hepatocyte growth factor (HGF) in the operative areas in the two groups. The sample number was 6. Data were statistically analyzed with independent sample t test. Results: On PID 7, 14, and 21, the hairs in the operative areas in dermal in situ reimplantation group were denser than those in dermal dislocation group. On PID 14, the skin cross section in the operative areas in dermal dislocation group showed a "sandwich"-like structure, while the skin cross section in the operative areas in dermal in situ reimplantation group had normal structure. On PID 7, 14, and 21, the skin thickness in the operative areas in dermal dislocation group was (4 234±186), (4 688±360), and (4 548±360) μm, respectively, which was close to (4 425±156), (4 714±141), and (4 310±473) μm in dermal in situ reimplantation group (P>0.05); the dermal thickness in the operative areas in dermal dislocation group was significantly thinner than that in dermal in situ reimplantation group (with t values of -9.73, -15.85, and -15.41, respectively, P<0.01); the fibrotic tissue thickness at the dermal-fat interface in the operative areas in dermal dislocation group was significantly thicker than that in dermal in situ reimplantation group (with t values of 14.48, 20.58, and 15.67, respectively, P<0.01); there was no statistically significant difference between the fibrotic tissue thickness at the dermal-fat interface and the dermal cutting interface in the operative areas in dermal in situ reimplantation group (P>0.05). On PID 7, 14, 21, the type Ⅲ collagen content in the dermal-fat interface in the operative areas in dermal dislocation group was increased significantly compared with that in dermal in situ replantation group (with t values of 2.65, 0.61, and 7.39, respectively, P<0.05 or P<0.01), whereas there were no statistically significant differences in the type Ⅰ collagen content at the dermal-fat interface in the operative areas between the 2 groups (P>0.05) and the type Ⅰ and Ⅲ collagen content between the dermal-fat interface and the dermal cutting interface in the operative areas in dermal in situ reimplantation group (P>0.05). On PID 7, 14, and 21, PCNA, TGF-β₁, FGF-2, and HGF were positively expressed in the superficial dermis and adipose tissue in the operative areas in dermal dislocation group, while PCNA, TGF-β₁, FGF-2, and HGF were positively expressed in the superficial dermis, deep dermis, and adipose tissue in the operative areas in dermal in situ reimplantation group. Conclusions: Inadequate intrinsic thickness of dermal tissue is the key factor causing fibrosis, and the biological purpose of fibrosis is to "compensate" the intrinsic thickness of the skin. Besides, adipose tissue may also be an important component of fibrotic skin repair.
Swine ; Female ; Animals ; Dermis/pathology* ; Proliferating Cell Nuclear Antigen/metabolism* ; Fibroblast Growth Factor 2 ; Cross-Sectional Studies ; Fibrosis ; Skin Diseases/pathology* ; Collagen/metabolism*

OBJECTIVETo observe dynamically the influence of the application of dermal template on the p53 gene expression and apoptosis during wound repairing in burn patients.

METHODSTwenty burn patients were enrolled in the study and were divided into experiment (E, n = 11) and control (C, n = 9) groups. The escharectomy wounds in patients with 3rd degree burn in E group were covered with dermal template overlain with thin split-thickness autograft, while those in C group were covered with thin split-thickness autograft only. Specimens were harvested from wounds of both groups at 1st, 2nd, 3rd, 4th and 5th post operative week (POW). The P53 expression and the apoptosis were assessed respectively by immunohistochemistry and by TUNEL kit. The change in cell number was observed after HE staining.

RESULTSThe P53 expression increased gradually along with the wound healing process from 1st to 4th POW, which was significantly higher than that in C group at 2nd, 3rd, and 4th POW (P < 0.05), and it reached the peak at 4th POW. Fibroblasts underwent apoptosis at 1st POW in E group, while apoptosis of the endothelial cells occurred mainly at 2nd and 3rd POW. There was obvious difference in the rate of apoptosis between the two groups in 3rd and 4th POW (P < 0.05). The numbers of fibroblasts and vascular endothelial cells in E group were smaller than those in C group.

CONCLUSIONApplication of dermal template overlain with thin split-thickness autograft to wounds could induce P53 expression and cell apoptosis, thereby reduce scar formation, resulting in improvement of the quality of wound healing.

Adult ; Apoptosis ; Burns ; metabolism ; pathology ; therapy ; Dermis ; transplantation ; Fibroblasts ; pathology ; Humans ; Skin Transplantation ; methods ; Transplantation, Autologous ; Transplantation, Heterologous ; Tumor Suppressor Protein p53 ; genetics ; Wound Healing ; Young Adult

OBJECTIVETo study the signal roles of protein tyrosine kinase (PTK) on proliferation and collagen synthesis of fibroblasts derived from hypertrophic scar(HS-FB) and normal skin (NS-FB) by interferon-gamma (IFN-gamma) or transforming growth factor beta1 (TGF-beta1).

METHODSHS-FB and NS-FB were cultured and passaged in Dulbecco's modified Eagle's medium(DMEM). The PTK activity in unstimulated or IFN-gamma or TGF-beta1-stimulated HS-FB and NS-FB (10,30,60 and 120 min) were assayed by phosphorus (32P) incorporation. Cell proliferation was determined with MTT stain. The type III procollagen was measured by radioimmunoassay.

RESULTSTGF-beta1 did not change PTK activity but it increased predominately proliferation and collagen synthesis of HS-FB and NS-FB in time-dependent fashion. Genistein, an inhibitor of PTK, inhibited HS-FB and NS-FB to proliferate and synthesize collagen but it could not change the roles on proliferation and collagen synthesis by TGF-beta1. IFN-gamma activated transiently PTK (P < 0.05) and increased proliferation and collagen synthesis of both fibroblast (P < 0.05, at 30 min, 60 min). As the recovery of PTK activity, the proliferation and collagen synthesis were inhibited by IFN-gamma at 120 min. Furthermore, Genistein abrogated the transient increased roles and partly reversed the longterm inhibitory functions by IFN-gamma (P < 0.05) . There were no difference on PTK activity, proliferation and collagen synthesis between HS-FB and NS-FB.

CONCLUSIONSPTK did not mediate the signal of TGF-beta1 but transduced the signal of transient increased roles of IFN-gamma. Inhibited or activated PTK might mediate the signal of decreasing or increasing proliferation and collagen synthesis of fibroblast.

Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Collagen ; biosynthesis ; Dermis ; metabolism ; Fibroblasts ; cytology ; metabolism ; Humans ; Interferon-gamma ; pharmacology ; Protein-Tyrosine Kinases ; metabolism ; Signal Transduction ; Transforming Growth Factor beta1 ; pharmacology ; Wound Healing

OBJECTIVETo investigate the influence of epidermis from different sources on the proliferation and metabolism of fibroblasts (Fb), and to explore its cause.

METHODSIn a co-culture system, normal Fb (A group) and cicatricial Fb(B group) from 10 patients with scar during proliferative stage were co-cultivated with own normal skin epidermis (NSE), respectively, without direct contact. In control groups (C group), cicatricial Fb was cultured alone. Normal Fb and cicatricial Fb from 10 patients with scar during maturation period were co-cultured with own normal skin epidermis as mentioned above, and divided into D, E and F groups. The cell number of FB, the amount of type I and III procollagen (PC I, PC III) in the supernatants and the PC I to PC III ratio were determined.

RESULTSTo compare the C with A group and the F with D group, Fb in C and F groups exhibited increased cell number and PC I , PC III amounts (P < 0.05), and decreased ratio of PC I to PC III (P < 0.05). To compare the B with C group, PC III contents in the cell supernatant was increased (P < 0.05), and the ratio of PCI to PC III decreased in B group (P < 0.05), there were no obvious difference in Fb cell number and the amount of PC I contents between B and C group. To compare the E with F group, the cell number of Fb, as well as PC I and PC III contents in cell supernatant were obviously decreased in E group (P < 0.05), but no obvious decrease was observed in the ratio of PC I and PC III. To compare the B with A group and the E with D group, the cell number and the PC I and PC III contents in B and E groups were evidently increased, while the ratio of PC I to PC III decreased markedly (2.20 +/- 0.27 vs 1.16 +/- 0.21 in A, B group, P < 0.05; 2.18 +/- 0.14 vs 1.93 +/- 0.26 in D, E group, P < 0.05).

CONCLUSIONNormal epidermis may play an important role in preventing hypertrophic scar by producing some bioactive substances.

Cell Line ; Cell Proliferation ; Cicatrix, Hypertrophic ; pathology ; Coculture Techniques ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Dermis ; cytology ; Epidermis ; cytology ; Extracellular Matrix ; Fibroblasts ; cytology ; metabolism ; Humans ; Wound Healing