Innovative Clinical Scenario Simulator for Step-by-Step Microsurgical Training.

BACKGROUND: Microsurgical training should be implemented with consideration of operative difficulties that occur in actual clinical situations. We evaluated the effectiveness of a novel clinical scenario simulator for step-by-step microsurgical training that progressed from conventional training to escalated training with additional obstacles. METHODS: A training device was designed according to multiple and intricate clinical microsurgery scenarios. Twenty surgical residents with no experience in microsurgery were randomly assigned to either the control group (conventional training curricula, n = 10) or the experimental group (step-by-step training courses, n = 10). After 4 weeks of laboratory practice, the participants were scheduled to perform their first microvascular anastomoses on patients in an operating room. The Global Rating Scale (GRS) scores and operative duration were used to compare microsurgical skills between the two groups. RESULTS: There were no significant differences in the participants' baseline characteristics before microsurgical training between the groups with respect to age, sex, postgraduate year, surgical specialty, or mean GRS score (p < 0.05). There were also no significant differences in recipient sites between the two groups (p = 0.735). After training, the GRS scores in both groups were significantly improved (p = 0.000). However, in the actual microsurgical situations, the GRS scores were significantly higher in the experimental than control group (p < 0.05). There was no significant difference in the operative duration between the two groups (p < 0.13). CONCLUSION: Compared with a traditional training program, this step-by-step microsurgical curriculum based on our clinical scenario simulator results in significant improvement in acquisition of microsurgical skills.

One stage reconstruction of mid-face fistulous defects after maxillary sinus carcinoma resection with chimeric perforator free flaps.

BACKGROUND: The reconstruction of large fistulous defects following the radical ablation of maxillary sinus carcinoma remains challenging. The procedure requires not only the coverage of both intra-nasal lining and cheek skin but also sufficient obliteration of dead space between the two surfaces. In this report, we present our experience on the reconstruction of through-and-through defects in the mid-face with poly-foliated chimeric perforator flaps. METHODS: Nine patients (five males and four females) who received a two-skin paddled and one muscle segment chimeric perforator flap reconstruction after maxillary sinus carcinoma ablation between March 2015 and December 2019 were retrospectively reviewed in authors' hospital. The mean age of the patients was 59.11. Six patients were diagnosed as squamous cell carcinoma, two as adenoid cystic carcinoma, and one as adenocarcinoma. Brown class IIIa defects were found in eight patients, and one patient had a Brown class IVa defect. The mean size of intra-nasal defect was 5.67 × 4.06 cm2 , and the mean size of facial skin defect was 8.94 × 6.56 cm2 . ALT flaps were used in five patients, LD flaps in four patients. The minor skin paddle was firstly inset to the mucosal defect site as the lining. Then, the muscle segment was inset to eliminate the dead cavity. Finally, the major skin paddle was inset to recover the cutaneous defect. RESULTS: In ALT group, the mean size of the minor skin paddle was 5.7 × 4.7 cm2 , and the mean size of the major skin paddle was 8.7 × 6.6 cm2 . In LD group, the mean size of the minor skin paddle was 6.88 × 4.38 cm2 , and the mean size of the major skin paddle was 11 × 7.75 cm2 .All donor sites were closed primarily. All flaps survived and no partial flap loss was encountered. The mean follow-up time was 14.67 months, and there were no major postoperative complications. CONCLUSION: The use of poly-foliated chimeric perforator free flaps can provide functional and aesthetic coverage for extensive through-and-through mid-face defects without significant donor-site morbidities.

Corrigendum: Regulation of microrna-497-targeting AKT2 influences tumor growth and chemoresistance to cisplatin in lung cancer.

[This corrects the article DOI: 10.3389/fcell.2020.00840.].

A finite element analysis on the biomechanical performance of implant-retained finger prostheses designed for Asians.

This study aims to explore the biomechanical performance of implant-retained finger prostheses of different lengths and diameters designed specifically for Asians under external loads from different directions by the finite element method. According to the metacarpophalangeal stumps (length: 4, 7, 10 mm, diameter: 3.5, 4.5 mm) retained in Asian patients with finger defects, six implant-retained finger prosthesis models of different lengths and diameters were designed in Solid Works 3D, transported to Abaqus, and constructed based on computerized tomography (CT). The finite element simulation of the finger prosthesis structure was performed using HyperMesh. The strain and stress distribution of the finger prosthesis models under three loads were calculated: axial force, lateral force, and lateral force with bending moments. As the load increased, the cancellous bone yielded first, while the dense bone and implant could withstand much higher loads than the cancellous bone. As the implant depth increased, the maximum strain of the cancellous bone increased significantly, but the effect of the implant diameter remained unclear. In addition, the structure could withstand large axial loads but was much less able to withstand both lateral forces and bending moments. The yielding and destruction of the implant-retained finger prostheses designed specifically for Asians are mainly attributed to cancellous bone. As the depth of the implants increases, the maximum strain of cancellous bone rises significantly. In addition, in the treatment of patients with finger defects, this method may be used to analyze and select which implant can withstand stronger stress according to the finger stumps of the patients with finger defects so that the most suitable implant and individual surgical plan for the patient can be designed.

Time-Resolved Extracellular Matrix Atlas of the Developing Human Skin Dermis.

Skin aging is a physiological issue that is still relatively poorly understood. Studies have demonstrated that the dermal extracellular matrix (ECM) plays important roles in skin aging. However, the roles of the changes in ECM characteristics and the molecules that are secreted to the extracellular space and are involved in the formation of the dermal matrix from birth to old age remain unclear. To explore the way in which the ECM microenvironment supports the functions of skin development across different age groups is also poorly understood, we used a decellularization method and matrisome analysis to compare the composition, expression, and function of the dermal ECM in toddler, teenager, adult, and elderly skin. We found that the collagens, glycoproteins, proteoglycans, and regulatory factors that support skin development and interact with these core ECM proteins were differentially expressed at different ages. ECM expression markers occurring during the process of skin development were identified. In addition, our results elucidated the characteristics of ECM synthesis, response to skin development, and the features of the ECM that support epidermal stem cell growth via the basement membrane during skin aging.

The use of free myocutaneous flap and implant reinsertion for staged cranial reconstruction in patients with titanium mesh exposure and large skull defects with soft tissue infection after cranioplasty: Report of 19 cases.

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.

Treatment of Severe Postburn Contracture of the Elbow via Distraction With External Circular Frame in Pediatric Patient.

BACKGROUND: Although external circular frame (ECF) has been widely used for the correction of knee and ankle deformities, few studies reported the use of ECF for the treatment of severe postburn elbow contracture and stiffness (SPECS). The purpose of this retrospective study was to investigate the effectiveness and safety of the distraction using ECF in treating SPECS. METHODS: After institutional review board approval, we implemented a retrospective single-center case series study composed of consecutive patients treated for SPECS at Chinese PLA General Hospital between January 2010 and January 2018. After scar release and skin grafting, distraction with ECF was performed for 4 to 6 weeks, and the frame was retained for 2 more weeks before removal. Four weeks of splinting and at least 1 year of rehabilitation were recommended. Patient demographics, active and passive range of motion (ROM) of the elbow at different time points (preoperative, postdistraction, and final follow-up), and complications were collected from the electronic medical record. The primary outcome was the long-term improvement of the ROM. Other outcomes included complications and recurrence. RESULTS: The ECF was used to treat SPECS in 6 patients (3 males and 3 females, average age of 11.7 ± 2.6 years). Scar release and distraction with ECF significantly increased both active (from 3° preoperative to 38.7° postdistraction) and passive (from 3.5° preoperative to 48.3° postdistraction) ROM over an average distraction duration of 5.2 weeks. The long-term improvement of active and passive ROM was 38° ± 13.4° and 46° ± 14.7°, respectively, over a median follow-up of 4.1 years. Pin-tract infection occurred in 2 patients and were treated with local wound care and oral antibiotics. A tendon readhesion developed in 1 of the 6 patients because of noncompliance with splinting and physiotherapy, and was treated with revision surgery. CONCLUSIONS: The 3C strategy (i.e., contracture release, coverage of the defect with skin grafting, and correction of articular angle with gradual distraction using the ECF) is able to increase the ROM with minor complications. We recommend distraction with ECF as part of the treatment arsenal, particularly for severe contractures in which 1-stage correction is unfeasible because of considerable soft tissue shortening.

The "Matrisome" reveals the characterization of skin keloid microenvironment.

Keloids are fibroproliferative dermal tumors of unknown origin that are characterized by the overabundant accumulation of extracellular matrix (ECM) components. The mechanism of keloid formation has remained unclear because of a poor understanding of its molecular basis. In this study, the dermal ECM components of keloids were identified and the pathological features of keloid formation were characterized using large-scale quantitative proteomic analyses of decellularized keloid biomatrix scaffolds. We identified a total of 267 dermal core ECM and ECM-associated proteins that were differentially expressed between patients with keloids and healthy controls. Skin mechanical properties and biological processes including protease activity, wound healing, and adhesion were disordered in keloids. The integrated network analysis of the upregulated ECM proteins revealed multiple signaling pathways involved in these processes that may lead to keloid formation. Our findings may improve the scientific basis of keloid treatment and provide new ideas for the establishment of keloid models.

Autologous skin-grafting surgery to prevent esophageal stenosis after complete circular endoscopic submucosal tunnel dissection: a case-matched controlled study.

BACKGROUND: The incidence of postoperative stenosis after endoscopic resection of wholly circumferential superficial esophageal squamous cell neoplasms (SESCNs) is extremely high. METHODS: Between January 2011 and April 2019, 19 patients who underwent autologous skin-grafting surgery (ASGS) after complete circular endoscopic submucosal tunnel dissection (ccESTD) were enrolled to form the ASGS group. Cases in the ASGS group were individually matched at a 1:1 ratio to cases undergoing fully covered esophageal stent (FCES) placement alone (FCES group) based on pathological diagnosis, curative resection, longitudinal length of ulceration, lack of stent migration, time to stent removal, follow-up period and operators. Baseline characteristics and treatment outcomes were compared between the two groups. RESULTS: Baseline characteristics were comparable between the ASGS group and the FCES group. The incidence of patients with esophageal stenosis after removal of the stent in the ASGS group was significantly reduced compared that in the FCES group (36.8% vs 78.9%, p = 0.020). Comparison of preventive methods (ASGS vs FCES alone) between the stenosis group and nonstenosis group revealed that ASGS accounted for a higher proportion than FCES alone in the nonstenosis group (p = 0.020). CONCLUSIONS: Compared with FCES placement alone, ASGS appeared to be more effective in preventing esophageal stenosis after ccESTD for SESCNs.

Matrisome Provides a Supportive Microenvironment for Skin Functions of Diverse Species.

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.

Regulation of MicroRNA-497-Targeting AKT2 Influences Tumor Growth and Chemoresistance to Cisplatin in Lung Cancer.

BACKGROUND: MicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear. METHODS: Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was conducted to confirm the target gene of miR-497. RESULTS: In this study, we found that miR-497 was significantly downregulated in tumor tissues and blood samples of lung cancer patients. To understand the potential mechanism of miR-497 in inhibiting tumor growth, we showed that miR-497 blocked the activation of AKT2 and regulated cell proliferation, cell migration, colony formation and increases chemosensitivity of H1299 cells to cisplatin by inhibiting AKT2. MiR-497 also inhibited tumor growth and suppressed expression of AKT2 at the protein and mRNA levels in mouse xenograft tumors. CONCLUSION: Taken together, our findings indicated that miR-497 suppresses the tumor growth by targeting AKT2, and the miR-497/AKT2 axis is a potential therapeutic target for NSCLC intervention.

Free Medial Plantar Flap Versus Free Dorsal Myocutaneous Flap for the Reconstruction of Traumatic Foot Sole Defects.

BACKGROUND: Trauma can cause large defects in the weight-bearing foot sole. The reconstruction of such defects poses a major challenge in providing a flap that is durable, sensate, and stable. The pedicled medial plantar flap has been commonly used for reconstructing heel and plantar forefoot defects; however, the ipsilateral instep region is usually compromised by trauma. The purpose of this article was to report the use of contralateral free medial plantar flaps for the coverage of weight-bearing plantar defects and to compare these with distant free flaps. METHODS: Between 2005 and 2019, 15 patients (10 men and 5 women) with weight-bearing foot plantar defects were treated with a contralateral medial plantar flap, 11 (7 men and 4 women) with either a latissimus dorsi flap or a scapular flap. The average age was 18.07 ± 10.14 years (range, 4-34 years) and 26.55 ± 13.05 years (range, 13-56 years), respectively. Surgery was performed as a primary or secondary reconstruction after a trauma by the same surgical team. RESULTS: The mean size of defects was 9.73 ± 3.55 × 6.43 ± 2.8 cm in the contralateral free medial plantar flap group and 17.14 ± 6.84 × 11.41 ± 4.29 cm in the free dorsal flap group. All flaps survived in both groups. In the instep flap group, the appearance was satisfactory, the flap was durable, and tactile sensation was preserved in all patients, and none required a revision procedure. Two patients experienced delayed union of the donor-site grafted skin. In the dorsal flap group, 5 patients complained of a partial necrosis or delayed union at the recipient site, and 9 developed recurrent ulcerations over the weight-\bearing area. Five patients achieved only partial sensation in the flap. CONCLUSIONS: The contralateral medial plantar flap provides superior appearance, duration, and sensation over distant muscle flaps, without recurrent ulcerations. However, dorsal myocutaneous flaps may be used as a substitute when the defects are beyond the maximum boundaries of the instep area or are combined with bone loss.

Autologous Skin-Grafting Surgery to Prevent Esophageal Stenosis After Complete Circular Endoscopic Submucosal Tunnel Dissection for Superficial Esophageal Neoplasms.

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.

Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose­derived stem cells into fibroblasts.

Fibroblasts are the major effector cells of skin wound healing. Adipose­derived stem cells can differentiate into fibroblasts under certain conditions. In the present study, it was hypothesized that adipose­derived 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.

Preclinical safety studies on autologous cultured human skin fibroblast transplantation.

Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) 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.

[Preliminary clinical observations on autologous cultured skin fibroblasts transplantation to treat the facial soft tissue deficiencies].

OBJECTIVE: To observe the effect and safety of autologous cultured skin fibroblasts transplantation for treating depressed facial skin defects. METHODS: A total of 19 patients were treated from Jan, 2010 to Oct, 2010. Autologous skin fibroblasts were separated from postauricular skin biopsy or resected skin tissue in other surgeries such as blepharoplasty. They were cultured and expanded with exclusive method. Cells (2 x 10(7)/ml) within three passages were injected intradermally at the site of skin depression three times at one-month interval. Adverse events were observed and recorded. Clinical effects were evaluated and graded by two unrelated physicians before and 6 months after the first injection. RESULTS: Cells from 16 patients were successfully cultured at the first time. The other 3 patients underwent a second harvest. A total amount of 6 x 10(8) cells could be reached within three passages in 45 days. 16 out of 19 patients accomplished the whole course of this study. Minor adverse events were observed in two patients including small ulcer caused by over injection in one patient and slightly redness and swelling in the other. The redness disappeared after a week without any treatment. No serious complications were observed. Significant difference was noticed between the scores obtained before and after the treatment. CONCLUSIONS: From this study, neither serious complications nor excessive cell proliferation or scar formation was found after cell injection. The effect of using autologous fibroblast transplantation was obvious and long-lasting, which provides a new choice for the treatment of depressed facial skin defects.