Fibroblasts are the major effector cells of skin wound healing. Adipose-derived stem cells can differentiate into fibroblasts under certain conditions. In the present study, it was hypothesized that adipose-derived stem cells (ADSCs) could be induced by the adipose extracellular matrix (ECM) to differentiate into fibroblasts in order to promote skin wound healing. First, flow cytometry was used to detect the ratio of fibroblasts and relative expression of the fibroblast markers cytokeratin 19 (CK19) and vimentin in ADSCs. Then, the effect of the adipose ECM during the differentiation of ADSCs into fibroblasts was investigated by detecting the total amount of collagen fibers and degree of fibrosis, and the proliferation and cell cycle of differentiated fibroblasts, using the MTT assay and flow cytometry analysis respectively. Finally, a mouse skin wound model was established and treated with PBS, ADSC suspension or ECM + ADSCs to compare wound healing rate and expression of collagen I and collagen III by immunohistochemistry. Following induction of ADSCs with the adipose ECM, more fibroblasts were found, expression of CK19 and vimentin increased, and a greater degree of fibrosis occurred, which revealed the positive effect of the adipose ECM on the differentiation of ADSCs into fibroblasts. In addition, the induced fibroblasts had enhanced proliferation activity, with more cells in the S phase and fewer in the G2/M phase. The in vivo experiment indicated that the ECM produced by the ADSCs had a faster wound healing rate and increased expression of collagen I and collagen III compared with mice injected with PBS or ADSCs alone, which verified that ADSCs induced by the adipose ECM had a positive effect on skin wound healing. The present study demonstrated that the adipose ECM in combination with ADSCs may be a novel therapeutic target for the repair of skin injury, due to the ability of the adipose ECM to induce the differentiation of ADSCs into fibroblasts and to facilitate the wound healing process.
Background Management of cranial defects following failed cranioplasty due to titanium mesh exposure and infection is challenging. The purpose of this report is to describe a modified technique using a free myocutaneous flap transfer for primary soft tissue reconstruction, and titanium mesh reinsertion for cranioplasty revision. Methods Nineteen patients with titanium mesh exposure and infection following cranioplasty were treated from January 2012 to January 2019. The average patient age was 41.89 years and the average size of the cranial defect was 7.74 × 13.92 cm. The reasons for craniotomy were craniocerebral trauma (n = 17), cerebrovascular disease (n = 1), and brain tumor (n = 1). The mean duration between implant exposure and current procedure was 7.16 months. Implant was removed and a free myocutaneous flap was designed to cover both scalp and cranium defects. After a mean duration of 12.32 months, implants were re‐inserted in a vascularized pocket at the second stage by elevating a plane between the previously transferred fascia layer and muscle layer. Results The average sizes of the muscle flaps and skin paddles were 7.74 × 13.92 cm and 4.97 × 8.97 cm. The average size of the implants was 8.24 × 14.42 cm. All flaps survived completely with no complication. After an average follow‐up of 48.16 months there were no cranioplasty failures. Functional coverage of craniectomy defect sites with normalized head contour was achieved. Conclusions The use of free myocutaneous flap and implant reinsertion achieved durable cranial and scalp defect reconstruction and aesthetic outcomes. The myocutaneous flap increases blood supply to the scalp, which may reduce the chances of infection and implant re‐exposure.
A biomaterial scaffold is a promising tool employed to drive tissue regeneration. This technology has been successfully applied in human tissue rebuilding, particularly for the skin. Meanwhile, there is still room for further improvement, such as maintaining sufficient functionality of a biomaterial scaffold. Here, we developed a new decellularization method to generate a complete anatomical skin biomatrix scaffold with a preserved extracellular matrix (ECM) architecture. We performed proteomic and bioinformatic analyses of the skin scaffold maps of humans, pigs, and rats and systematically analyzed the interaction between ECM proteins and different cell types in the skin microenvironment. These interactions served to quantify the structure and function of the skin's Matrisome comprising core ECM components and ECM-associated soluble signaling molecules required for the regulation of epidermal development. We primarily found that the properties of the skin ECM were species-specific. For example, the composition and function of the ECM of the human skin were more similar to those of pigs compared with those of rats. However, the skin ECM of the pig was significantly deficient in its enzyme systems and immune regulatory factors compared with that of humans. These findings provide a new understanding of the role of the skin ECM niche as well as an attractive strategy that can apply tissue engineering principles to skin biomatrix scaffold materials, which promises to accelerate and enhance tissue regeneration.
OBJECTIVES: To assess the safety and effectiveness of autologous skin-grafting surgery (ASGS) for preventing esophageal stenosis after complete circular endoscopic submucosal tunnel dissection (ccESTD) for superficial esophageal neoplasms. METHODS: Between October 2017 and March 2018, 8 patients who underwent ccESTD and ASGS were included. We assessed the occurrence of esophageal stenosis and adverse events. RESULTS: No adverse events occurred, including perforation, bleeding, wound infection, or stent migration. Five patients did not experience stenosis over a median follow-up of 7 months. CONCLUSIONS: ASGS appeared to be a safe and effective way to prevent esophageal stenosis after ccESTD.
Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV TM ) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts.
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