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Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability, tunable pore sizes (80-200 µm), and appropriate compressive modulus (10.8 kPa) is manufactured from self-healable hydrogel under different gelling times through Schiff reaction between chitosan and difunctionalized polyurethane (DFPU). Bioactive molecules (Y27632 and dexamethasone) are respectively loaded in the top and bottom layers to form the Y27632/dexamethasone-loaded trilayer cryogel (Y/DEX-TC). Mesenchymal stem cells (MSCs) seeded in Y/DEX-TC proliferated ≈350% in vitro and underwent chondrogenesis or osteogenesis in response to the respective release of Y or DEX in 14 days. Acupuncture is administered to animals in an attempt to modulate the innate regulatory system and mobilize endogenous MSCs for osteochondral defect regeneration. In vivo rabbit experiments using Y/DEX-TC combined with acupuncture successfully regulate SDF-1 and TGF-β1 levels, which possibly cause MSC migration toward Y/DEX-TC. The synergistic effect of cryogel and acupuncture on immunomodulation is verified with a ≈7.3-fold enhancement of the M2-/M1-macrophage population ratio by treatment of Y/DEX-TC combining acupuncture, significantly greater than ≈1.5-fold increase by acupuncture or ≈2.2-fold increase by Y/DEX-TC alone. This novel strategy using acellular drug-loaded cryogel and accessible acupuncture shows promise in treating osteochondral defects of joint damage., (© 2024 Wiley‐VCH GmbH.)

In this study, the chemical components of ethanol extract from the aromatic parts of Syringa oblata were systematically separated and purified by silica gel column chromatography, thin layer plate preparation and liquid phase preparation. Combined with ultraviolet analyzer(UV), infrared analyzer(IR), nuclear magnetic resonance analyzer(NMR), high resolution mass spectrometer(HR-ESI-MS), X-ray diffraction and other spectrum technology as well as literature physicochemical data comparison methods for structural identification, a total of 10 compounds were identified. They were identified as oblatanoid D(1),(-)-T-muurolol(2), oblatanoid E-G(3-5), 14-noreudesma-3-hydroxy-3-en-2,9-dione(6), 1-isopropyl-2,7-dimethylnaphthalene(7), isocoradiol(8), α-calacorene(9), cadin-4-en-1-β-ol(10). Compound 1 is a new sesquiterpene compound that has not been reported, and the other 9 compounds are isolated from S. oblata for the first time. The compound 1 has a significant protective effect on the LPS-induced inflammatory injury model of RAW264.7 cells.

Background: The skin is the largest organ in the human body and serves as a barrier for protective, immune, and sensory functions. Continuous and permanent exposure to the external environment results in different levels of skin and extracellular matrix damage. During skin wound healing, the use of good dressings and addition of growth factors to the wound site can effectively modulate the rate of wound healing. A dressing containing bioactive substances can absorb wound exudates and reduce adhesion between the wound and dressing, whereas growth factors, cytokines, and signaling factors can promote cell motility and proliferation., Aim and Objectives: We prepared a functional wound dressing by combining platelet-rich plasma (PRP) and zwitterionic hydrogels. Functional wound dressings are rich in various naturally occurring growth factors that can effectively promote the healing process in various types of tissues and absorb wound exudates to reduce adhesion between wounds and dressings. Furthermore, PRP-incorporated zwitterionic hydrogels have been used to repair full-thickness wounds in Sprague-Dawley rats with diabetes (DM SD)., Materials and Methods: Fibroblasts and keratinocytes were cultured with PRP, zwitterionic hydrogels, and PRP-incorporated zwitterionic hydrogels to assess cell proliferation and specific gene expression. Furthermore, PRP-incorporated zwitterionic hydrogels were used to repair full-thickness skin defects in DM SD rats., Results: The swelling ratio of hydrogel, hydrogel + PRP1000 (108 platelets/mL), and hydrogel + PRP1000 (109 platelets/mL) groups were similar (~07.71% ± 1.396%, 700.17% ± 1.901%, 687.48% ± 4.661%, respectively) at 144 hours. The tensile strength and Young modulus of the hydrogel and hydrogel + PRP10000 groups were not significantly different. High concentrations of PRP (approximately 108 and 109 platelets/mL) effectively promoted the proliferation of fibroblasts and keratinocytes. The zwitterionic hydrogels were not cytotoxic to any cell type. High PRP concentration-incorporated zwitterionic hydrogels increased the rate of cell proliferation and significantly increased the expression of characteristic genes such as collagen, fibronectin, involucrin, and keratin. Subsequently, zwitterionic hydrogels with high PRP concentrations were used to repair full-thickness skin defects in DM SD rats, and a wound healing rate of more than 90% was recorded on day 12., Conclusions: PRP contains high concentrations of growth factors that promote cell viability, enhance specific gene expression, and have a high medical value in cell therapy. Zwitterionic hydrogels have a 3-dimensional interconnected microporous structure and can resist cell adhesion without causing cytotoxicity. Platelet-rich plasma-incorporated zwitterionic hydrogels further enhance the cellular properties and provide an effective therapeutic option for wound healing., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Necrotizing fasciitis is a surgically diagnosed infection of the deep soft tissues that results in high mortality. It is usually caused by aerobic and anaerobic bacteria and group A Streptococcus . Metallosis is characterized by the deposition of metal debris in the blood that causes metal poisoning and tissue damage. The abrasion of metal components that occurs after joint replacements causes metallosis, which may lead to severe complications. We report a rare case of metallosis-induced necrotizing fasciitis of the right thigh. Metallosis should be considered as a cause of necrotizing fasciitis if the patient has had a joint replacement surgery.

The reconstruction of defects of the lateral malleolus involving the exposed fibular bone or tendon is challenging. This study aimed to evaluate the clinical application of the peroneal artery perforator flap with or without split-thickness skin grafting for soft tissue reconstruction of the bony defect of the lateral malleolus of the ankle joints. Reconstruction using a peroneal artery perforator flap with or without split-thickness skin grafting was performed for 15 patients (10 men, 5 women) between January 2007 and December 2018. The mean age was 53.7 years, and the mean size of the flaps was 40 cm 2 . The flaps were elevated in the form of a perforator flap, and split-thickness skin grafting was performed over the flaps and adjoining raw areas. The flaps survived in all cases; however, partial necrosis was observed in 3 cases. In cases of small-sized defects of the lateral malleolus of the ankle joints where a flap is required for the exposed bone or tendon, reconstruction using the peroneal artery perforator flap is advantageous, since the morbidity rate of the donor site is low and soft tissue is reconstructed.

Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1 HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of β1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chronic cutaneous wounds from tissue trauma or extensive burns can impair skin barrier function and cause severe infection. Fabrication of a customizable tissue-engineered skin is a promising strategy for regeneration of uneven wounds. Herein, a planar-/curvilinear-bioprintable hydrogel is developed to produce tissue-engineered skin and evaluated in rat models of chronic and irregular wounds. The hydrogel is composed of biodegradable polyurethane (PU) and gelatin. The hydrogel laden with cells displays good 3D printability and structure stability. The circular wounds of normal and diabetes mellitus (DM) rats treated with planar-printed tri-cell-laden (fibroblasts, keratinocytes, and endothelial progenitor cells (EPCs)) hydrogel demonstrate full reepithelization and dermal repair as well as large amounts of neovascularization and collagen production after 28 days. Furthermore, the curvilinear module is fabricated based on the corresponding wound topography for curvilinear-bioprinting of the irregular tissue-engineered skin. The large and irregular rat skin wounds treated with curvilinear-printed tri-cell-laden hydrogel demonstrate full repair after 28 days. This planar-/curvilinear-bioprintable tri-cell-laden hydrogel shows great potential for customized biofabrication in skin tissue engineering., (© 2022 Wiley-VCH GmbH.)

Background: Diabetic foot and leg ulcers are a major cause of disability among patients with diabetes mellitus. A topical gel called ENERGI-F703, applied twice daily and with adenine as its active pharmaceutical ingredient, accelerated wound healing in diabetic mice. The current study evaluated the safety and efficacy of ENERGI-F703 for patients with diabetic foot and leg ulcers., Methods: This randomized, double-blind, multicenter, phase II trial recruited patients from eight medical centers in Taiwan. Patients with intractable diabetic foot and leg ulcers (Wagner Grade 1-3 without active osteomyelitis) were randomly assigned (2:1) to receive topical ENERGI-F703 gel or vehicle gel twice daily for 12 weeks or until complete ulcer closure. The investigator, enrolled patients and site personnel were masked to treatment allocation. Intention to treat (ITT) population and safety population were patient to primary analyses and safety analyses, respectively. Primary outcome was complete ulcer closure rate at the end of treatment. This trial is registered with ClinicalTrials.gov, number NCT02672436., Findings: Starting from March 15 th , 2017 to December 26 th , 2019, 141 patients were enrolled as safety population and randomized into ENERGI-F703 gel (n = 95) group or vehicle gel (n = 46) group. In ITT population, ENERGI-F703 (n = 90) and vehicle group showed ulcer closure rates of 36.7% (95% CI = 26.75% - 47.49%) and 26.2% (95% CI = 13.86% - 42.04%) with difference of 9.74 % (95 % CI = -6.74% - 26.23%) and 25% quartiles of the time to complete ulcer closure of 69 days and 84 days, respectively. There were 25 (26.3%) patients in ENERGI-F703 group and 11 (23.9%) patients in vehicle group experiencing serious adverse events and five deaths occurred during the study period, none of them related to the treatment., Interpretation: Our study suggests that ENERGI-F703 gel is a safe and well-tolerated treatment for chronic diabetic foot and leg ulcers. Further studies are needed to corroborate our findings in light of limitations., Funding: Energenesis Biomedical Co., Ltd., Competing Interests: This project was sponsored by Energenesis Biomedical Co. Ltd. Han-Min Chen, Jiun-Tsai Lin, Yi-Fang Cheng, Guang-Huar Young, Chun-Fang Huang, Ya-Chun Kuo are current employees of Energenesis Biomedical Co., Ltd. All other authors have no conflicts of interest to declare., (© 2022 The Authors.)

This was the first study to analyse patients who sustained severe self-induced burns from this common Asian practice. There is a need to raise public awareness and physician attention about the consequences of preventable burn injuries and the importance of first aid in patients with diabetic neuropathy. Retrospective data on 16 consecutive patients who had diabetes and neuropathy admitted to the plastic surgery ward at the Tri-Service General Hospital from January 1, 2015, to February 2, 2021 with burn injuries because of heat applications were collected and analysed for this study. Age, gender, season, first aid adequacy, comorbidity, interventions, total body surface area (TBSA), degree of burn, aetiology, length of stay (LOS), and status at discharge were reviewed. The mean age of the 16 patients was 65.13 years. The most common burn aetiology was contact (50%), followed by scald (37.5%) and radiation burns (12.5%). TBSA burn averaged ± standard deviation 1.54 ± 1.22. Seven patients (44%) had wound infections, and three patients underwent amputations. The average LOS was 28.2 days. Asian practice of heat application is the common aetiology of severe and preventable burn injuries. Education about neuropathy and the consequences of a burn injury should be provided to patients with diabetes., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

The strain-stiffening and self-healing capabilities of biological tissues enable them to preserve the structures and functions from deformation and damage. However, biodegradable hydrogel materials with both of these biomimetic characteristics have not been explored. Here, a series of strain-stiffened, self-healing hydrogels are developed through dynamic imine crosslinking of semiflexible O -carboxymethyl chitosan (main chain) and flexible dibenzaldehyde-terminated telechelic poly(ethylene glycol) (crosslinker). The biomimetic hydrogels can be reversibly stiffened to resist the deformation and can even recover to their original state after repeated damages. The mechanical properties and stiffening responses of the hydrogels are tailored by varying the component contents (1-3%) and the crosslinker length (4 or 8 kDa). A combinatorial system of in situ coherent small-angle X-ray scattering with rheological testing is developed to investigate the network structures (in sizes 1.5-160 nm) of hydrogels under shear strains and reveals that the strain-stiffening originates from the fibrous chitosan network with poly(ethylene glycol) crosslinking fixation. The biomimetic hydrogels with biocompatibility and biodegradability promote wound healing. The study provides an insight into the nanoscale design of biomimetic strain-stiffening self-healing hydrogels for biomedical applications.

Background: Breast reconstruction is an integral part of breast cancer treatment, and implant-based breast reconstruction is the most commonly used method worldwide. However, there is still no technique that allows surgeons to predict the volume of the required implant. Although computed tomography and magnetic resonance imaging provide adequate representations of the breast, these procedures are time-consuming, expensive, and expose patients to radiation. Therefore, there is a need for safer, noninvasive alternatives for preoperative breast volume measurements., Patients and Methods: This study is a prospective review of 12 patients with early-stage breast cancer who underwent nipple-sparing mastectomy and immediate breast reconstruction with implants. Preoperatively, the Artec Eva 3D scanner was used to acquire volumetric measurements of the breasts. Intraoperatively, the volume of the mastectomy specimen was measured using the water displacement method. Correlations among the preoperative breast, mastectomy specimen, and estimated and final implant volumes were analyzed through Pearson correlation coefficient. A correction prediction factor of 85% was applied where necessary. Patient and physician satisfaction were evaluated 3 months postoperatively., Results: Our study found a statistically significant correlation between the preoperative breast volumes measured by the Artec Eva 3D scanner and intraoperative mastectomy specimen volumes (r = 0.6578). There was no correlation between the preoperative breast volumes and final implant volumes, mastectomy specimen volumes and final implant volumes, and estimated implant volumes and final implant volumes., Conclusions: Although the Artec Eva 3D scanner can offer relatively accurate measurement of breast volumes, multiple studies still need to be done to determine how these data can be applied to the mastectomy procedure and breast implant selection. It may be more applicable for preoperative planning in breast augmentation surgery. Future surgeons should also take into account that variabilities in natural breast size, tumor size, cancer stage, and in patient and physician preferences all influence the outcome of breast reconstruction surgery., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The adipose-derived stromal vascular fraction (SVF) is considered to be an attractive source of stem cells in cell therapy. Besides stem cells, it also contains functional cells, such as macrophages, precursor cells, somatic stem cells, and pericytes. Collagenase digestion is the most frequently used method to isolate SVF, but it is time-consuming and costly and has some problems, such as infectious agents and immune reactions. In this research, we compared the yield, cell population ratios, and cell viability when isolating SVF by the ultrasonic physics (U-SVF) method and traditional enzymatic method (E-SVF). Then, we isolated exosomes from U-SVF and E-SVF, respectively, and cocultured them with fibroblasts to investigate the potential of applying this cell secretion in wound repair. The results showed that there was no significant difference between the ultrasonic method and enzymatic method in terms of cell viability, cell numbers, or the expression of CD markers of stem cells. However, exosome analysis identified a greater number and smaller size of exosome particles obtained by U-SVF. In terms of cell proliferation efficiency, although the proliferation efficiency of U-SVF was lower than that of E-SVF. Trilineage differentiation experiments revealed that both E-SVF and U-SVF had good differentiation ability, owing to high stem cell content. Finally, E-SVF and U-SVF exosomes were cocultured with fibroblasts. The efficiency of fibroblast migration increased in the SVF exosome treated groups, and the expression of related genes (integrin α5β1) was slightly upregulated; however, the expression of FAK, AKT, ERK, and RhoA was significantly upregulated at 24 hours. From the abovementioned experiments, we found that there was no significant difference in stem cell-related characteristics between SVF isolated by ultrasonic cavitation and SVF isolated by the enzymatic method. In addition, exosomes secreted by SVF may have excellent therapeutic effect on skin injuries, which provides a new viewpoint and therapeutic strategy for soft tissue repair., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In this study, we aimed to analyze the clinical efficacy of closed-incision negative pressure wound therapy (CiNPWT) when combined with primary closure (PC) in a patient with pressure ulcers, based on one single surgeon's experience at our medical center., Methods: We retrospectively reviewed the data of patients with stage III or IV pressure ulcers who underwent reconstruction surgery. Patient characteristics, including age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, application of CiNPWT to reconstructed wounds, duration of hospital stay, and wound complications were analyzed., Results: Operation time (38.16 ± 14.02 vs. 84.73 ± 48.55 min) and duration of hospitalization (36.78 ± 26.92 vs. 56.70 ± 58.43 days) were shorter in the PC + CiNPWT group than in the traditional group. The frequency of debridement (2.13 ± 0.98 vs. 2.76 ± 2.20 times) was also lower in the PC + CiNPWT group than in the traditional group. The average reconstructed wound size did not significantly differ between the groups (63.47 ± 42.70 vs. 62.85 ± 49.94 cm 2 ), and there were no significant differences in wound healing (81.25% vs. 75.38%), minor complications (18.75% vs. 21.54%), major complications (0% vs. 3.85%), or mortality (6.25% vs. 10.00%) between the groups., Conclusions: Our findings indicate that PC combined with CiNPWT represents an alternative reconstruction option for patients with pressure ulcers, especially in those for whom prolonged anesthesia is unsuitable.

Necrotizing fasciitis is a severe deep soft tissue infection with poor disease prognosis. The Aeromonas species is characterized as gram-negative, facultative, anaerobic small bacilli that are ubiquitously distributed in aquatic environments. Necrotizing fasciitis caused by this species is rare but has an extremely high mortality rate, especially in immunocompromised individuals. This study presents the case of a 39-year-old man with alcoholic liver cirrhosis, Child-Pugh class B, with necrotizing fasciitis caused by Aeromonas hydrophila . Despite debridement and bilateral above-knee amputation performed immediately, rapid progression to bilateral upper limbs and trunk was noted in 24 hours. The patient expired from septic shock with multiple organ failure in less than 48 hours following initial presentation. Two similar cases with different medical intervention and results have been reported in the literature and are further discussed in the present study. This allows the authors to suggest potential solutions for an improved clinical outcome.

Background and Objective: To deal with burn mass casualty incidents (BMCIs), various countries have established national or regional BMCI emergency response plans (ERPs). A burn care capacity ranking model for hospitals can play an integral role in ERPs by providing essential information to emergency medical services for distributing and handling mass burn patients. Ranking models vary across countries and contexts. However, Taiwan has had no such model. The study aims to develop a ranking model for classifying hospitals' burn care capacity in preparation for the development of a national BMCI ERP., Methods: Multiple methods were adopted. An expert panel provided consultations on data selection and clustering validation. Data on 116 variables from 535 hospitals were collected via open data platforms under the Ministry of Health and Welfare. Data selection and streamlining was conducted to determine 42 variables for cluster analysis. SAS 9.4 was used to analyze the data set -via a hierarchical cluster analysis using Ward's method, followed by a tree-based model analysis to identify the criteria for each cluster. Both internal and external cluster validation were performed., Results: Four clusters of burn care capacity were determined to be a suitable number of clusters. All hospitals were arranged into capacity levels accordingly. Results of the Kruskal-Wallis test showed that the difference between clusters were significant. Tree-based model analysis revealed four determining variables, among which the refined level of emergency care responsibility hospital was found to be most influential on the clustering process. Responses from the questionnaire were used as an external validation tool to corroborate with the cluster analysis results., Conclusion: The use of open government data and cluster analysis was suitable for developing a ranking model to determine hospitals' burn care capacity levels in Taiwan. The proposed ranking model can be used to develop a BMCI emergency response plan and can also serve as a reference for using cluster analysis with open government data to rank care capacity or quality in other domains., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract: Skin grafts are not suitable for closing tendon- or bone-exposing wounds, which require flap surgery. Dermal regeneration templates have value for closing such wounds, but the disadvantages of the technique include implantation failures because of infection, hematoma formation, or inappropriate immobilization. Negative-pressure wound therapy was reported to increase graft acceptance in difficult wounds.This retrospective case series of 65 patients evaluated negative-pressure therapy combined with artificial dermis for the treatment of acute or chronic tendon- or bone-exposing wounds. The artificial dermis was placed after adequate wound-bed preparation, with simultaneous application of a vacuum-assisted closure system. Split-thickness skin grafting was performed after the implanted artificial dermis had become established.The overall success rate was 88.1% (59/67): 88.6% (39/44) in the chronic wounds group and 87% (20/23) in the acute-trauma group separately. The overall mean survival time of artificial dermis in success cases was 13.24 ± 7.14 days. In separately, the survival time of artificial dermis had no statistically difference in chronic wound group (13.64 ± 7.53 vs 12.60 ± 5.86. P = .943), but had significant statistical difference in acute trauma group (12.45 ± 6.44 days vs 23.33 ± 4.04 days, P = .018). Also, comorbidity of PAOD was found a strong risk factor of failure in chronic wound group (100% vs 23.1%, P < 0.001).We concluded that artificial dermis combined with negative-pressure therapy followed by split-thickness skin grafting might be a reliable and effective option for surgical reconstruction of tendon- or bone-exposing wounds, and could decreasing waiting periods of autologous skin graft., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Astragaloside IV (AS-IV) is a natural herb extract and a popular compound used in traditional Chinese medicine because of its effect on multiple biological processes, such as promotion of cell proliferation, improvement in cardiopulmonary and vascular function, and promotion of angiogenesis around wounds, leading to accelerated wound healing. Vascular regeneration primarily results from the differentiation of endothelial progenitor cells (EPCs). Biomedical acceleration of angiogenesis and differentiation of EPCs around the wound remain challenging., Materials and Methods: In this study, we treated human umbilical cord blood-derived EPCs with AS-IV and cultured them on 2-dimensional (tissue culture polystyrene) and 3-dimensional culture plates (3DPs). These cultured cells were then combined with human blood plasma gel and applied on the skin of nude mice in an attempt to repair full-thickness skin defects., Results: The results show that using 3DP culture could increase vascular-related gene expression in EPCs. Furthermore, 12.5 μg/mL AS-IV-treaded EPCs were combined with plasma gels (P-3DP-EPC12.5) and showed enhanced vascular-related protein expression levels after 3 days of culture. Finally, P-3DP-EPC12.5s were used to repair full-thickness skin defects in nude mice, and we could register a wound healing rate greater than 90% by day 14., Conclusions: Based on these results, we concluded that we have developed a potential therapeutic approach for wound healing using plasma gel containing 3-dimensional surface-cultured AS-IV-treated EPCs., Competing Interests: Conflicts of interest and sources of funding: Financial support for this work was provided by the National Defense Medical Center, Tri-Service General Hospital, ROC (TSGH-C107-119), Zouying Branch of Kaohsiung Armed Forces General Hospital, Republic of China (ZBH 107-18), and Chi Mei Medical Center (CMNDMC-10610). Additional financial support was provided by Chunghwa Pharmaceutical Research Foundation, Taiwan, Republic of China., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Unhealed chronic wounds often deteriorate into multiple infection with several kinds of bacteria and excessive proteolytic wound exudate and remains one of the common healthcare issues. Here, the functional and antimicrobial hydrogel and cryogel biomaterials were prepared from glycol chitosan and a novel biodegradable Schiff base crosslinker difunctional polyurethane (DF-PU). The cryogel exhibited ~2730 ± 400% of water absorption with abundant macropores and 86.5 ± 1.6% of porosity formed by ice crystal as well as ~240% cell proliferation effect; while the hydrogel demonstrated considerable antimicrobial activity and biodegradability. As an optimized procedure to treat the diabetic skin wound in a rat model, the combined application of adipose stem cell-seeded cryogel/hydrogel biomaterials on the wound and acupuncture surrounding the wound may attain 90.34 ± 2.3% of wound closure and secure the formation of granulation tissue with sufficient microvessels and complete re-epithelialization in 8 days. The average increases in the superficial temperature of wounded animals after acupuncture were about 1-2 °C. Through the activation of C3a and C5a, the increased secretion of cytokines SDF-1 and TGFβ-1, as well as the down-regulation of proinflammatory cytokines TNF-α and IL-1β, the combined treatment of stem cell-seeded cryogel/hydrogel biomaterials and acupuncture on wounds produced synergistic immunomodulatory effects. The strategy using the combined treatment of biomaterials, stem cells, and acupuncture reveals a perspective new approach to accelerate the tissue regeneration., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Abstract: Preserving both esthetic and functional outcome remains challenging in facial burn injuries. The major issue is the initial treatment of injury. In this study, we focused on patients with partial-thickness facial burns admitted to the burn unit of Tri-Service General Hospital, Taipei, from November 2016 to November 2018. In 21 included patients, customized mask-style, transparent hydrogel-based dressing was applied to the burns. The mean age of included patients was 37.4 years. The mean area of burn injury was 11.9% of total body surface area, and the mean area of second-degree facial burns was 162.3 cm2. Full reepithelialization took, on average, 10.86 days. Scarring was acceptable in terms of texture and color, and no hypertrophic or keloidal scarring was noted. The mean Vancouver Scar Scale score was 2.07. Use of the hydrogel-based dressing masks seems to be a promising means of reducing pain, providing uninterrupted wound healing, facilitating observation, and positively affecting scarring in patients with second-degree facial burns., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The homeostasis of intracellular pH (pH i ) affects many cellular functions. Our previous study has established a functional and molecular model of the active pH i regulators in human induced pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pH i buffering power (β) and to investigate the effects of extracellular pH and Na + -H + exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pH i was detected by microspectrofluorimetry with pH-sensitive dye-BCECF. Western blot, immunofluorescence staining, and flow cytometry were used to detect protein expression and pluripotency. Our study in hiPSCs showed that (a) the value of total (β tot ), intrinsic (β i ), and CO 2 -dependent ( β C O 2 ) buffering power all increased while pH i increased; (b) during the spontaneous differentiation for 4 days, the β values of β tot and β C O 2 changed in a tendency of decrease, despite the absence of statistical significance; (c) an acidic cultured environment retained pluripotency and further upregulated expression and activity of NHE1 during spontaneous differentiation; (d) inhibition on NHE1 activity promoted the loss of pluripotency. In conclusion, we, for the first time, established a quantitative model of passive β during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs., (© 2020 Wiley Periodicals LLC.)

Introduction: Proper wound care along with the use of skin grafts over deep burn wounds has been the standard treatment. However, the goal in burn wound care has shifted from achieving a satisfactory survival rate to improving long-term form and function of the healed wound, which is sometimes hindered by scar contracture. This has prompted surgeons to find alternative ways to treat burn wounds without compromising function. Among burn cases, hand injuries are the most problematic when it comes to delicate function recovery., Methods: This study presents the results of conjunctive use of a bilayer artificial dermis, negative pressure wound therapy, and split-thickness skin grafts for grafting over acute burn wounds and scar-releasing defects after severe hand burns., Results: Three months after the operation, the scar was soft and pliable, the aesthetic outcome was good, and the patients gained much improvement in hand function and quality oflife., Conclusions: The combined technique achieved a good scar quality and aesthetic effect on burned hands as well as excellent functional outcome, which resulted in major improvements and an independent life for the patient., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Currently, there are no harmonized guidelines which govern skin banking in the Asia Pacific region. Therefore, skin banks are either unregulated or rely on their nation's legislation or international accreditation to uphold their quality standards. A new set of skin banking guidelines was developed through a comprehensive review and collation of best international practices for the Asia Pacific Burn Association (APBA) members, from donor screening and testing, to skin recovery, processing, storage and distribution, and quality assurance. National regulatory requirements reviewed include the European directives, Australia's Therapeutic Goods Administration and Singapore's tissue banking standards. Further technical and quality management recommendations are referenced from the American Association of Tissue Banks (AATB), the United States Food and Drug Administration standards and guidance documents, various relevant European guides, Japanese Society of Tissue Transplantation guidelines and the Asia Pacific Association of Surgical Tissue Banking. Adapted mainly from the AATB standards, the new Asia Pacific Burn Association Guidelines for Skin Banking in Therapeutic Applications offer a comprehensive manual, addressing: governance and contracts; staff responsibilities; quality management; facilities, equipment and supplies management; donor consent and testing; and recommendations of good practices pertaining to skin recovery, processing, storage and distribution. Besides complementing current generic regulations, they provide technical specifications of major aspects unaddressed in most legislations. This inaugural set of new regional skin banking guidelines would be a start for regional members of the APBA to adopt, and will hopefully culminate in a set of standards so that, in the long run, skin allografts from this region can be of similar quality, which can simplify import process and facilitate the exchange of allografts between members., (© The Author(s) 2020. Published by Oxford University Press.)

Purpose: To study outcomes among survivors of the mass-casualty powder explosion on 27 June 2015, at Formosa Fun Coast Waterpark, New Taipei City, Taiwan., Methods: Using retrospective data on Taiwanese survivors, we analyzed prehospital management, burns assessment and prognosis, functional recovery, and medical costs, followed-up through 30 June 2017. We related outcomes to burn extent, categorized according to the percentages of total body surface area with second/third-degree burns (%TBSA) or autologous split-thickness skin grafts (%STSG), and an investigational scale: f{SASG} = (%TBSA + %STSG)/2, stratified by %STSG. Analyses included casualty dispersal, comparisons between %TBSA, %STSG and f{SASG}, and their relationships with length of hospitalization, times to rehabilitation and social/school re-entry, physical/mental disability, and medical costs. We also investigated how burn scars restricting joint mobility affected rehabilitation duration., Results: 445 hospitalized casualties (excluding 16 foreigners, 23 with 0% TBSA and 15 fatalities) aged 12-38 years, had mean TBSA of 41.1%. Hospitalization and functional recovery durations correlated with %TBSA, %STSG and f{SASG} - mean length of stay per %TBSA was 1.5 days; more numerous burn scar contractures prolonged rehabilitation. Females had worse burns than males, longer hospitalization and rehabilitation, and later school/social re-entry; at follow-up, 62.3% versus 37.7% had disabilities and 57.7% versus 42.3% suffered mental trauma (all p ≤ 0.001). Disabilities affecting 225/227 people were skin-related; 34 were severely disabled but 193 had mild/moderate impairments. The prevalence of stress-related and mood disorders increased with burn extent. Treatment costs (mean USD-equivalents ∼$48,977/patient, ∼$1192/%TBSA) increased with burn severity; however, the highest %TBSA, %STSG and f{SASG} categories accounted for <10% of total costs, whereas TBSA 41-80% accounted for 73.2%., Conclusions: Besides %TBSA, skin-graft requirements and burn scar contractures are complementary determinants of medium/long-term outcomes. We recommend further elucidation of factors that influence burn survivors' recovery, long-term physical and mental well-being, and quality of life., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Piwi-interacting RNAs (piRNAs) dysregulation occurs frequently in extensive cancers. However, there was no report about piRNA expression in esophageal cancer (EC). In this study, the expression levels of piR-823 and DNMT1, DNMT3A, DNMT3B were detected in 54 pairs of ESCC tissues and adjacent normal tissues using the quantitative real-time polymerase chain reaction method. Pearson's chi-squared test and receiver operating characteristic curves were established to evaluate the diagnostic and prognostic value of piR-823 in ESCC. Spearman's correlation analysis was used to evaluate the association between piR-823 and DNMTs. We found that piR-823 was significantly upregulated in ESCC tissues compared with matched normal tissues (P = 0.0213), the level of piR-823 was significantly associated with lymph node metastasis (P = 0.042). The ROC curve analysis of piR-823 expression level yielded an area under the ROC curve value of 0.713 (P = 0.0001). DNMT3B was upregulated in ESCC tissues compared with matched normal tissues (P = 0.0286). There was an obvious positive correlation between piR-823 and DNMT3B expression (r = 0.6420, P < 0.0001). In conclusion, for the first time, we provided evidence about piRNA expression in EC. piRNA-823 and DNMT3B were both upregulated in ESCC and positively correlated with each other, suggesting the tumor oncogenic role of piR-823 in ESCC to epigenetically induce aberrant DNA methylation through DNMT3B. In addition, piRNA-823 showed high specificity in detecting ESCC and higher piRNA-823 level indicated higher risk of lymph node metastasis, suggesting its diagnostic and prognostic biomarker potential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

In this study, a novel antiadhesion membrane made of polycaprolactone, gelatin, and chitosan was fabricated using the electrospinning technique. A series of polycaprolactone/gelatin/chitosan (PGC) electrospun membranes with different amounts of chitosan (0%, 0.5%, 1%, and 2% in weight percentage) was synthesized. The physicochemical properties and biocompatibility of the fabricated membranes were examined and compared with the aim to select an effective antiadhesion membrane. Scanning electron microscopy showed that these 4 electrospun membranes had similar fiber diameter and pore area, with no statistical differences between them. Furthermore, the contact angle decreased with increased chitosan content, indicating that chitosan may contribute to increased hydrophilic properties. The in vitro degradation test revealed that the higher chitosan content corresponded to a lower degradation rate in PGC membranes within 7 days. All PGC membranes exhibited similar cell proliferation; however, cell proliferation was lower than tissue culture polystyrene (P < 0.05). To compare antiadhesion ability, the adhesion between the cecum and abdominal wall was created in a rat model. Assessment after implantation of electrospun membranes revealed that PGCs with higher chitosan content (PGC2) had better antiadhesion effects, as evaluated by an adhesion score at day 14 postsurgery. Thus, PGC2 was effective in reducing the formation of tissue adhesion. Therefore, PGC electrospun membrane may provide a potential peritoneal antiadhesion barrier for clinical use.

Rationale: The main cause of death in melanoma patients is widespread metastases as it can metastasize to almost every organ. However, melanoma skeletal muscle metastases (MSMM) are exceptional, and only a few cases of MSMM to the rectus abdominis muscles have been previously described. And our case maybe the first reported case in Asia region., Patient Concerns: A 45-year-old man with history of right scalp melanoma, pT3aN0M0, stage IIA status post wide excision with 2 cm safe margin and right neck lymph node dissection at 5 years before. He had an almost 5 years disease-free period but presented to our clinic due to intermittent abdominal sharp pain for 1 to 2 months, with a palpable soft tissue mass over his right abdomen. Metastatic melanoma to rectus abdominis muscles was highly suspected., Interventions: The patient subsequently underwent radical en-block extraperitoneal 15 cm segmental resection of the right rectus abdominis muscle including tumor mass. The resected tumor was a black-gray colored solid mass, and the final histologic study showed a metastasis of melanoma., Outcomes: Postoperative course of the patient was uneventful, and the right abdominal pain was improved. The patient was referred for further target therapy, but passed away half a year later due to multiple metastasis., Lessons: Scalp melanoma with isolated rectus muscle metastasis is extremely rare especially for a young aged patient who had an almost 5-year disease-free period. Surgery is a potentially curative therapy for patients with isolated metastatic melanoma. The goal is negative resection margins, in order to avoid local recurrences. Radical compartmental surgery should be considered for selected stage IV melanoma patients with sole rectus abdominis MSMM, whose disease could be amenable to complete resection, in preliminary procedure to prolong disease-free survival time. For oligometastatic disease, surgical resection is sometimes useful in carefully selected patients after systemic therapy; also, it could be performed as symptomatic treatment.

A mass casualty incident (MCI) can have an enormous impact on an already crowded emergency department (ED), affecting the quality of health care provided to non-MCI ED patients. On June 26, 2015, a burn MCI (BMCI) occurred due to a cornstarch explosion at a party at a water park. The competing needs of the BMCI patients might have crowded out the needs of the non-BMCI patients. Although crowd-out effects have been previously documented in a variety of health care situations, they have not been extensively evaluated during MCIs. We aimed to determine whether the outcomes of the non-MCI patients were compromised during this incident.We conducted a retrospective observational study comparing several health care parameters and outcomes between non-BMCI patients and historical controls during the designated period using institutional electronic records and the National Health Insurance Research Database.On the night of the incident, 53 patients were sent to our ED; most of them arrived within 3 hours after the BMCI. There was a significant increase in the wait time for ICU beds among non-BMCI patients compared to the wait times during the corresponding week of the previous year (8.09 ± 4.21 hours vs 3.77 ± 2.15 hours, P = .008). At the hospital level, there was a significantly increased length of hospital stay (LOS) in the ICU after the MCI compared with the LOS in the ICU in the same week of the preceding year (median days: 15 vs 8, P ≤ .001). At the regional level, there were no significant differences between the 2 periods in the LOS in acute care, LOS in the ICU or mortality rates at the involved medical centers.Crowd-out effects from the MCI occurred in the ED and at the institutional level. Although there was an increased wait time for admission to the ICU and a longer LOS in the ICU, the LOS in acute care beds, treatment of time-sensitive diseases, and mortality rates were not compromised by the current MCI protocol at either the institutional or regional levels.

Three-dimensional (3D) printing technology has rapidly developed as a promising technology for manufacturing tissue engineering scaffolds. Cells used in tissue engineering are subjected to the quality management and risk of contamination, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this study, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature (-40 °C) to fabricate tissue engineering scaffolds with sequential drug release function. The scaffolds containing 200 ng/ml SDF-1 and 22 wt% Y27632-encapsulated microspheres (55 µg/ml Y27632 in microspheres) (abbreviated PU/SDF-1/MS&#95;Y scaffolds) had the optimal performance. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro and reach the effective concentration (∼100 ng/ml and 3.38 µg/ml, respectively) after the appropriate time (24 h and 62 h, respectively). Human mesenchymal stem cells (hMSCs) seeded in the scaffolds showed significant GAG deposition in 7 days. Besides, the gradual release of SDF-1 from the PU/SDF-1/MS&#95;Y scaffolds could induce the migration of hMSCs. Implantation of the cell-free PU/SDF-1/MS&#95;Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. The 3D printed scaffolds with sequential releases of SDF-1 and Y27632 may have potential in cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: The clinical success of tissue engineering depends highly on the quality of externally supplied cells, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this manuscript, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature to fabricate tissue engineering scaffolds with sequential drug release function. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro. SDF-1 was released earlier from the scaffolds to promote cell migration. The drug Y27632 was released later from the microspheres into the matrix of the scaffolds to induce the chondrogenic differentiation of the attracted cells. Implantation of the cell-free PU/SDF-1/MS&#95;Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. We hypothesized that the cell-free scaffolds may improve the clinical applicability and convenience without the use of exogenous cells or growth factor., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Early initiation of enteral nutrition improves clinical outcomes in critical patients with serious burns. Post-pyloric tube feeding is a valuable therapeutic option for severely burned patients with poor gastric emptying. How early post-pyloric feeding can be initiated to provide more benefits to patients has not yet been examined. A fire erupted at a recreational water park in New Taipei City, Taiwan, on June 27, 2015. The results of early initiation versus delayed post-pyloric feeding in severely burned patients in this mass-casualty incident were compared. Door-to-post-pyloric feeding time ≤ 24 h was considered as early post-pyloric feeding (EPF) and that > 24 h was considered as delayed post-pyloric feeding (DPF). Thirteen patients with severe burn injuries (> 40% of the total body surface area) were assigned to undergo either EPF (five patients) or DPF (eight patients). This study is a "fortuitously controlled" study, and the authors were able to formulate and test whether EPF is better than DPF by comparing the two groups. In patients in the EPF, the intake of calories increased rapidly and was maintained throughout the study period. In addition, rapid restoration of plasma magnesium concentrations as well as pronounced recovery of platelet count in the EPF group was observed. In conclusion, our findings indicate that the time from injury to the onset of post-pyloric feeding is crucial, and EPF allows for the administration of calculated caloric needs. Therefore, EPF can be successfully initiated with beneficial outcomes of nutritional reconstruction in severely burned patients.

Background: A tissue-engineered skin substitute, based on gelatin ("G"), collagen ("C"), and poly(ε-caprolactone) (PCL; "P"), was developed., Method: G/C/P biocomposites were fabricated by impregnation of lyophilized gelatin/collagen (GC) mats with PCL solutions, followed by solvent evaporation. Two different GC:PCL ratios (1:8 and 1:20) were used., Results: Differential scanning calorimetry revealed that all G/C/P biocomposites had characteristic melting point of PCL at around 60 °C. Scanning electron microscopy showed that all biocomposites had similar fibrous structures. Good cytocompatibility was present in all G/C/P biocomposites when incubated with primary human epidermal keratinocytes (PHEK), human dermal fibroblasts (PHDF) and human adipose-derived stem cells (ASCs) in vitro . All G/C/P biocomposites exhibited similar cell growth and mechanical characteristics in comparison with C/P biocomposites. G/C/P biocomposites with a lower collagen content showed better cell proliferation than those with a higher collagen content in vitro . Due to reasonable mechanical strength and biocompatibility in vitro , G/C/P with a lower content of collagen and a higher content of PCL (GC L P H ) was selected for animal wound healing studies. According to our data, a significant promotion in wound healing and skin regeneration could be observed in GC L P H seeded with adipose-derived stem cells by Gomori's trichrome staining., Conclusion: This study may provide an effective and low-cost wound dressings to assist skin regeneration for clinical use., Competing Interests: The authors declare there are no competing interests.

The pigment melanin is produced by melanocytes, is primarily responsible for skin color, and protects it against ultraviolet rays that can cause the destruction of genetic material within the keratinocytes. To elucidate the mechanisms of many diseases associated with melanocytes, such as melanoma and albinism, or burns with uneven pigment distribution, the disease model needs to be established first. In this study, we aimed to construct the melanocyte model from patients in a short period.Sandai virus vector containing 4 stemness genes (Oct4, Sox2, Klf4, c-Myc) was transfected into human adipose-derived stem cells to produce induced pluripotent stem cells (iPSCs). Immunofluorescence staining was used to confirm the expression of specific proteins for iPSCs, including Tra-1-60, Tra-1-81, Oct-4, Sox-2, and Nango. polymerase chain reaction results also showed that specific genes of iPSCs with the ability to cause the differentiation of cells into the 3 germ layers were expressed. In our in vivo experiments, iPSCs were subcutaneously injected into nude mice to induce teratoma formation for 2 months. The morphology of the 3 germ layers was confirmed by hematoxylin and eosin staining. Furthermore, melanocytes were purified by serial induction medium, and their presence was confirmed by flow cytometry and the expression of different markers for melanocytes.

Introduction: Reconstruction of segmental peripheral nerve gap is still challenging when the autografts are unavailable owing to limited availability of donor site and functional recovery. The creation of artificial conduits composed of biological or synthetic materials is still developing. Acellular dermal matrix (ADM) has been widely studied and its extension and plasticity properties may become suitable nerve conduits under different forms of nerve gaps. Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell types of different germ layers including neural stem cells (NSCs). The purpose of this experiment is to use ADM as a scaffold combined with NSCs induced by ADSCs to establish neural tissue engineering., Methods: The ADSCs were isolated from syringe-liposuction adipose tissue harvested from abdominal fat and then cultured in keratinocyte serum free media to trigger into neural stem cells. Stem cells were confirmed by the expression of surface markers nestin and SOX2 in NSCs with Western blot and immunofluorescent staining. Matrix enzyme treatment was used to obtain ADM to remove immunogenic cells while maintaining the integrity of the basement membrane complex and the extracellular matrix structure of the dermis. The NSCs were cocultured with ADM for 3 days, and survival markers Ki67 and neural stem cell markers nestin were detected., Results: These NSCs can form neurospheres and express nestin and SOX2. The NSC can further coculture with ADM, and it will continue to express survivor markers and neural stem cell markers on ADM., Conclusions: These findings provide evidence that the combination of ADM and NSC has the same potential as neural tissue engineering as other acellular sciatic nerve.

Aim: To establish a functional and molecular model of the intracellular pH (pH i ) regulatory mechanism in human induced pluripotent stem cells (hiPSCs)., Methods: hiPSCs (HPS0077) were kindly provided by Dr. Dai from the Tri-Service General Hospital (IRB No. B-106-09). Changes in the pH i were detected either by microspectrofluorimetry or by a multimode reader with a pH-sensitive fluorescent probe, BCECF, and the fluorescent ratio was calibrated by the high K + /nigericin method. NH 4 Cl and Na-acetate prepulse techniques were used to induce rapid intracellular acidosis and alkalization, respectively. The buffering power (β) was calculated from the ΔpH i induced by perfusing different concentrations of (NH 4 ) 2 SO 4 . Western blot techniques and immunocytochemistry staining were used to detect the protein expression of pH i regulators and pluripotency markers., Results: In this study, our results indicated that (1) the steady-state pH i value was found to be 7.5 ± 0.01 ( n = 20) and 7.68 ± 0.01 ( n =20) in HEPES and 5% CO 2 /HCO 3 - -buffered systems, respectively, which were much greater than that in normal adult cells (7.2); (2) in a CO 2 /HCO 3 - -buffered system, the values of total intracellular buffering power (β) can be described by the following equation: β tot = 107.79 (pH i ) 2 - 1522.2 (pH i ) + 5396.9 (correlation coefficient R 2 = 0.85), in the estimated pH i range of 7.1-8.0; (3) the Na + /H + exchanger (NHE) and the Na + /HCO 3 - cotransporter (NBC) were found to be functionally activated for acid extrusion for pH i values less than 7.5 and 7.68, respectively; (4) V-ATPase and some other unknown Na + -independent acid extruder(s) could only be functionally detected for pH i values less than 7.1; (5) the Cl - / OH - exchanger (CHE) and the Cl - /HCO 3 - anion exchanger (AE) were found to be responsible for the weakening of intracellular proton loading; (6) besides the CHE and the AE, a Cl - -independent acid loading mechanism was functionally identified; and (7) in hiPSCs, a strong positive correlation was observed between the loss of pluripotency and the weakening of the intracellular acid extrusion mechanism, which included a decrease in the steady-state pH i value and diminished the functional activity and protein expression of the NHE and the NBC., Conclusion: For the first time, we established a functional and molecular model of a pH i regulatory mechanism and demonstrated its strong positive correlation with hiPSC pluripotency., Competing Interests: Conflict-of-interest statement: All authors declare no potential conflict of interest.

The basic principle of donor site selection is to take skin from areas that will heal with minimal scarring while balancing the needs of the recipient site. For skin loss from the lower legs and feet, the most common harvest site for split-thickness skin grafts is the anterior or posterior thigh; grafts from the plantar areas have been mostly used to cover the volar aspect of digits and palms. Between September 2015 and September 2017, 42 patients with areas of skin loss on the legs or feet were treated with plantar skin grafts because of their cosmetic benefits and the convenience of the surgical procedure and postoperative wound care. Our technique of harvesting a single layer of split-thickness skin graft (0.014 in. thick) from a non-weight-bearing area of the foot of the injured leg is simple and provided good functional and cosmetic outcomes at both the donor and recipient sites. All patients were very satisfied with the recovery progress and final results. Therefore, in the management of skin defects in the lower legs or feet that comprise less than 1.5% of the total body surface area, our surgical method is a reliable alternative to anterior or posterior thigh skin grafting., (© 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Skin substitutes with existing vascularization are in great demand for the repair of full-thickness skin defects. In the present study, we hypothesized that a pre-vascularized skin substitute can potentially promote wound healing. Novel three-dimensional (3D) skin substitutes were prepared by seeding a mixture of human endothelial progenitor cells (EPCs) and fibroblasts into a human plasma/calcium chloride formed gel scaffold, and seeding keratinocytes onto the surface of the plasma gel. The capacity of the EPCs to differentiate into a vascular-like tubular structure was evaluated using immunohistochemistry analysis and WST-8 assay. Experimental studies in mouse full-thickness skin wound models showed that the pre-vascularized gel scaffold significantly accelerated wound healing 7 days after surgery, and resembled normal skin structures after 14 days post-surgery. Histological analysis revealed that pre-vascularized gel scaffolds were well integrated in the host skin, resulting in the vascularization of both the epidermis and dermis in the wound area. Moreover, mechanical strength analysis demonstrated that the healed wound following the implantation of the pre-vascularized gel scaffolds exhibited good tensile strength. Taken together, this novel pre-vascularized human plasma gel scaffold has great potential in skin tissue engineering.

Background: Tendon adhesion is a serious problem and it affects tendon gliding and joint motion. Although recent studies have yielded promising results in developing anti-adhesion materials, there are still many problems. Polycaprolactone (PCL)-based polyurethane (PU) has good mechanical properties and biocompatibility, and it has a potential in anti-adhesion applications., Materials and Methods: In this study, a series of waterborne biodegradable polyurethane (WBPU) films with different ratios of ionic groups were synthesized. In order to select an effective anti-adhesion film, the WBPU films were cast and characterized for physicochemical properties and biocompatibility., Results: All WBPU films were non-cytotoxic in the cell viability test and had suitable physicochemical and mechanical properties based on the measurement of zeta potential, water contact angle, mechanical properties, water absorption, thickness change, and gelatin test. To evaluate the anti-adhesion effect, severely injured tendons of rabbits were sutured with the modified Kessler core suture technique and WBPU films were then wrapped around the tendon. Implantation in rabbits showed that the WBPU film had better anti-adhesion effect than PCL films and the untreated control, and demonstrated no significant difference in the anti-adhesion performance from the commercial product Seprafilm based on gross evaluation, histological analysis, and biomechanical assessment., Conclusion: Compared to Seprafilm and PCL applied in the tendon anti-adhesion, WBPU had better mechanical properties, low inflammatory reaction, and a proper degradation interval., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: To treat skin color disorders, such as vitiligo or burns, melanocytes are transplanted for tissue regeneration. However, melanocyte distribution in the human body varies with age and location, making it difficult to select the optimal donor skin to achieve a desired color match. Determining the correlations with the desired skin color measurement based on CIELAB color, epidermal melanocyte numbers, and melanin content of individual melanocytes is critical for clinical application., Method: Fifteen foreskin samples from Asian young adults were analyzed for skin color, melanocyte ratio (melanocyte proportion in the epidermis), and melanin concentration. Furthermore, an equation was developed based on CIELAB color with melanocyte ratio, melanin concentration, and the product of melanocyte ratio and melanin concentration. The equation was validated by seeding different ratios of keratinocytes and melanocytes in tissue-engineered skin substitutes, and the degree of fitness in expected skin color was confirmed., Results: Linear regression analysis revealed a significant strong negative correlation ( r  =  - 0.847, R 2  = 0.717) between CIELAB L * value and the product of the epidermal melanocyte ratio and cell-based melanin concentration. Furthermore, the results showed that an optimal skin color match was achieved by the formula., Discussion: We found that L * value was correlated with the value obtained from multiplying the epidermal melanocyte ratio (R) and melanin content (M) and that this correlation was more significant than either L * vs M or L * vs R. This suggests that more accurate prediction of skin color can be achieved by considering both R and M. Therefore, precise skin color match in treating vitiligo or burn patients would be potentially achievable based on extensive collection of skin data from people of Asian descent., Competing Interests: The authors declare there are no competing interests.

Background: Loss of soft tissue in heel-calcaneal region is frequently caused by trauma, infection, or tumors. Limited availability of similar tissue becomes challenging, therefore, the use of free tissue transfer offers a solution. Our aim is to describe long term functional outcome of different free tissue transfers for these defects., Patients and Methods: We retrospectively reviewed 24 consecutive cases of the heel-calcaneal defect between January 2009 and December 2014. The free fasciocutaneous perforator (FCP) flaps were performed in 14 cases and free muscle flaps with skin graft in 10 cases. The postoperative complications, range of motion and ability of ambulation or exercise were administered to evaluate functional results., Results: The average follow-up period was 26.5 months. The survival of free flap was 100%. Early complication included venous thrombosis, infection and edge dehiscence was noted in 8 cases. Late complication with insensate ulcers developed in 3 cases (1 cases in FCP flap, 2 cases in muscle flap). All ulcers healed spontaneously without surgical intervention. The postoperative average range of motion of ankle regained 52.79 degree in FCP flap group and 56.4 degree in muscle flap group. The ability of ambulation or exercise returned in 13 cases in FCP group (13/14) and 9 cases in muscle flap group (9/10). No differences of complication rate (P = .403), ROM (P = .363) or functional evaluation (P = .803) could be found between these two groups., Conclusions: Both FCP flap and muscle flaps provided the similar and excellent functional results in resurfacing of heel-calcaneal defects after long term follow up., (© 2017 Wiley Periodicals, Inc.)

Despite advances in reconstruction techniques, ischial pressure ulcers continue to present a challenge for the plastic surgeon. The purpose of this retrospective study was to evaluate outcomes of using an oblique downward gluteus maximus myocutaneous (GMM) flap for coverage of grade IV ischial ulcers. Data regarding defect size, flap size, operation time, duration of wound healing, and surgical outcome were abstracted from the medical records of patients whose ischial pressure ulcers had been reconstructed using GMM island flaps between January 2010 and December 2015. The 22 patients comprised 15 men and 7 women with a mean age of 52 (range 16-81) years. Twenty (20) had paraplegia, 6 had a recurrent ischial ulcer, 2 were bedridden following a cerebrovascular accident, 1 had a myelomeningocele status post operation, and 19 were spinal cord injury patients. Follow-up time ranged from 6 to 40 months. Pressure ulcer size ranged from 3 cm x 2 cm to 10 cm x 5 cm (average 22.3 cm2). The average flap size was 158 cm2 (15.9 cm x 9.7 cm); the largest was 286 cm2 (22 cm x 13 cm). The operating time ranged from 52 minutes to 110 minutes (average, 80 minutes). In 2 cases, wound dehiscence occurred but completely healed after resuturing. One (1) ischial pressure ulcer recurred 6 months following surgery and was successfully covered with a pedicled anterolateral thigh flap. No recurrences or problems were observed in the remaining 20 patients. Time to complete wound healing ranged from 14 to 24 days (average 17.8 days). Treatment of ischial pressure ulcers with GMM flaps allowed for an easy, simple procedure that provided the adequate thickness of soft tissue needed to cover the bony prominence, fill dead space, and cover the lesion. This technique was a reliable and safe reconstructive modality for the management of ischial pressure ulcers, even in recurrent cases.

Platelet-rich plasma (PRP) is a kind of plasma that is rich in platelets after processing. It includes various growth factors and cytokines, which speed up the process of wound healing and hemostasis. The PRP solution used in this study is diluted from lyophilized PRP powder, which decreased the possibility of contamination, facilitated the storage, and prolonged the storage life. From in vitro fibroblast proliferation testing, the numbers of PRP supplement were performed for 1, 4, and 7 times by continuous replacement of culture medium each day. Four times of lyophilized PRP supplement was selected for clinical study due to sufficient promotion of fibroblast proliferation. Next, 27 patients of deep second-degree burn wound were included in this study. Patients were assigned to two groups: PRP group (n = 15) and control group (n = 12). A concentration of 1.0 × 10 platelets/cm (wound area) according to wound size was sprayed on the wound evenly. Function was mainly assessed by the percentage of wound closure and bacteria picking out rate in 2 and 3 weeks. The wound closure at 3 weeks showed a significant difference in PRP group (P < 0.05). The healing rate of PRP group reached nearly 80% and made a breakthrough of 90% in 3 weeks, showing a significant difference compared with the control group (P < 0.05). Lyophilized PRP can be considered as an effective treatment to increase healing rate in patients with deep second-degree burn injury.

Background: Adequate fluid titration during the initial resuscitation period of major burn patients is crucial. This study aimed to evaluate the feasibility and efficacy of a goal-directed fluid resuscitation protocol that used hourly urine output plus the arterial waveform analysis FloTrac (Edwards LifeSciences, Irvine, Calif) system for major burns to avoid fluid overload., Methods: We conducted a retrospective cohort study of 43 major burn patients at the Tri-Service General Hospital after the Formosa Fun Coast Dust Explosion on June 27, 2015. Because of the limited capacity of intensive care units (ICUs), 23 intubated patients were transferred from the burn wards or emergency department to the ICU within 24 hours. Fluid administration was adjusted to achieve a urine output of 30 to 50 mL/h, cardiac index greater than 2.5 L/min/m, and stroke volume variation (SVV) less than 12%. The hourly crystalloid fluid infusion rate was titrated based on SVV and hourly urine output., Results: Of the 23 critically burned patients admitted to the ICU, 13 patients who followed the goal-directed fluid resuscitation protocol within 12 hours postburn were included in the analysis. The mean age (years) was 21.8, and the mean total body surface area (TBSA) burned (%) was 68.0. The mean Revised Baux score was 106.8. All patients sustained inhalation injury. The fluid volumes administered to patients in the first 24 hours and the second 24 hours (mL/kg/% total body surface area) were 3.62 ± 1.23 and 2.89 ± 0.79, respectively. The urine outputs in the first 24 hours and the second 24 hours (mL/kg/h) were 1.13 ± 0.66 and 1.53 ± 0.87, respectively. All patients achieved the established goals within 32 hours postburn. In-hospital mortality rate was 0%., Conclusions: The SVV-based goal-directed fluid resuscitation protocol leads to less unnecessary fluid administration during the early resuscitation phase. Clinicians can efficaciously manage the dynamic body fluid changes in major burn patients under the guidance of the protocol.

Many types of flaps are available if surgical reconstruction of a pressure ulcer is indicated, including a gluteus maximus flap, V-Y advancement flap, and superior gluteal artery perforator flap. Regional flap failure can complicate treatment, requiring additional flap surgery. An 80-year old woman with a 2-year history of being unconscious following a cerebrovascular accident presented with a Stage 4 sacral pressure ulcer of 2 months' duration with eschar and abscess formation. Because the wound measured 15 × 10 cm2, bilateral V-Y advancement flaps were used for surgical closure. However, 1 week later, ischemic change of the wound edges and wound dehiscence were observed. The wound was subsequently closed with an artery perforator (IGAP) flap, an approach that took into consideration religious preference of keeping the body intact. The patient was discharged with a healed wound 6 weeks postoperatively; long-term postoperative surveillance was hindered by the patient's distance from the care facility (she lived on an outlying island). This is the first case report to describe IGAP flap application in a patient with a sacral pressure ulcer after failed reconstruction using bilateral V-Y advancement flaps.

Significant skin pigmentation changes occur when patients suffer deep burn injuries. These pigmentation disorders may cause not only cosmetic and psychological issues, but more importantly it increases the risk of skin cancer or photoaging. Severe burns significantly effect on the process of repigmentation as the pigmentation is tightly regulated by cell proliferation and differentiation of melanocytes and melanocyte stem cells which are housing in the epidermis and hair follicles of the skin. In the present review, we discuss the possible mechanisms to replenish the melanocytes from the healthy epidermis and hair follicles surrounding burn wounds. The molecular mechanisms of skin repigmentation following healing of burn injuries includes the differentiation of melanoblasts into melanocytes, the distribution and responses of melanocytes and melanocyte stem cells after burn injury, and the regulation of melanin production. We also reviewed advanced therapeutic strategies to treat pigmentation disorders, such as convectional surgery, laser, UV treatment and emerging concepts in skin tissue-engineering., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pressure sores are often observed in patients who are bedridden. They can be a severe problem not only for patients and their caregivers but also for plastic surgeons. Here, we describe a new method of superior gluteal artery perforator flap harvesting and anchoring with the assistance of intraoperative indocyanine green fluorescent angiography. In this report, we describe the procedure and outcomes for 19 patients with grades III and IV sacral pressure sores who underwent the operation between September 2015 and November 2016. All flaps survived, and two experienced wound-edge partial dehiscence. With the assistance of this imaging device, we were able to acquire a reliable superior gluteal artery perforator flap and perform modified operations with it that are safe, easy to learn and associated with fewer complications than are traditional., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Alginate is a natural rich anionic polysaccharide (APS), commonly available as calcium alginate (CAPS). It can maintain a physiologically moist microenvironment, which minimises bacterial infection and facilitates wound healing at a wound site. Patients with burn injuries suffer from pain and an inflammatory response. In this study, we evaluated the CAPS dressing and traditional dressing containing carboxymethyl cellulose (CMC) for wound healing and scar tissue formation in a burn model of rat and swine. In our pilot study of a burn rat model to evaluate inflammatory response and wound healing, we found that the monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β were up-regulated in the CAPS treatment group. Next, the burn swine models tested positive for MCP-1 in a Gram-positive bacterial infection, and there was overproduction of TGF-β during the burn wound healing process. Rats were monitored daily for 1 week for cytokine assay and sacrificed on day 28 post-burn injury. The swine were monitored over 6 weeks. We further examined the pain and related factors and inflammatory cytokine expression in a rodent burns model monitored everyday for 7 days post-burn. Our results revealed that the efficacy of the dressing containing CAPS for wound repair post-burn was better than the CMC dressing with respect to natural wound healing and scar formation. The polysaccharide-enriched dressing exerted an antimicrobial effect on burn wounds, regulated the inflammatory response and stimulated anti-inflammatory cytokine release. However, one pain assessment method showed no significant difference in the reduction in levels of adenosine triphosphate in serum of rats after wound dressing in either the CAPS or CMC group. In conclusion, a polysaccharide-enriched dressing outperformed a traditional dressing in reducing wound size, minimising hypertrophic scar formation, regulating cytokines and maximising antimicrobial effects., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Vibrio vulnificus can cause severe skin and soft tissue infection (SSTI). The pathogen is an opportunistic marine bacterium that is likely to infect patients with chronic liver disease, patients in an immunocompromised state, and those in end-stage renal disease. V. vulnificus gains entry through soft tissues by direct penetration of a wound by infected marine organisms, such as raw oysters, shellfish and other seafood, or by exposing a wound to contaminated water. Despite its ease of entry, V. vulnificus necrotising fasciitis with compartment syndrome has rarely been described. We report a case of an elderly patient with end-stage renal disease undergoing haemodialysis, who developed necrotising fasciitis following infection by V. vulnificus through a puncture injury while cleaning fish. A successful salvage and reconstruction surgery was performed using fenestrated-type artificial dermis followed by negative pressure wound therapy. This case presents a reasonable treatment option for threatening V. vulnificus necrotising fasciitis with compartment syndrome., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Despite major advances in therapeutic strategies for the management of patients with severe burns, significant morbidity and mortality is observed. Hyperbaric oxygen therapy (HBOT) increases the supply of oxygen to burn areas. The aim of this study was to determine whether HBOT is effective in the treatment of major thermal burns., Methods: On June 27, 2015 in New Taipei, Taiwan, a mass casualty disaster occurred as fire erupted over a large crowd, injuring 499 people. Fifty-three victims (20 women and 33 men) were admitted to Tri-Service General Hospital. Thirty-eight patients underwent adjunctive HBOT (HBOT group), and 15 patients received routine burn therapy (control group). Serum procalcitonin (PCT) level, a sepsis biomarker, was measured until it reached normal levels (<0.5μg/L). The records of all patients from June 2015 to March 2016 were analyzed retrospectively. Outcome measures that were compared between the groups included the use of tracheostomy and hemodialysis, total body surface area (TBSA) and the number of skin graft operations, length of hospital stay, infection status, and mortality., Results: The mean age of the patients was 22.4 years, and the mean TBSA was 43%. All the patients survived and were discharged without requiring limb amputation or being permanently disabled. Patient characteristics did not differ significantly between the groups. PCT levels returned to normal significantly faster (p=0.007) in the HBOT group., Conclusion: Multidisciplinary burn care combined with adjunctive HBOT improves sepsis control compared with standard treatment without HBOT. Prospective studies are required to define the role of HBOT in extensive burns., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Background: Reconstruction of extensive defects of the lower abdomen, penoscrotum, trochanter, groin and knee without using complex microsurgery is a reconstructive challenge. Pedicled anterolateral thigh (ALT) flaps offer many advantages over other regional flaps for this purpose, such as the large skin area and soft-tissue availability, a remarkable pedicle length, and possessing multiple components and reliability. We present our experience of using pedicled ALT flaps for repairing various defects., Methods: From September 2006 to December 2013, 42 pedicled ALT flaps were used in 41 patients for defects of the lower abdomen (three patients), trochanter (26 patients), penoscrotum (10 patients), groin (one patient) and knee (one patient). Twenty-eight were men and 13 were women, and their mean age was 70.5 years (range, 22-103 years). The characteristics of the patients' age, sex, cause, flap size, flap component, follow-up and donor sites were recorded., Results: The flap size ranged from 8 × 5 cm (40 cm 2 ) to 11 × 18 cm (198 cm 2 ). The length of the pedicle ranged from 9 to 16 cm, which was enough to reach the defect without tension. No surgery-related mortality occurred. In 34 flaps, donor sites were closed primarily and eight underwent split-skin grafting. Satisfactory coverage was achieved in all patients., Conclusion: Our experience has shown the wide arc of rotation, large skin replacement potential, multiple components and reliability of pedicled ALT flaps. They are technically simple to apply as myocutaneous/fasciocutaneous flaps with minimal donor site morbidity., (© 2015 Royal Australasian College of Surgeons.)

Zwitterionic poly(sulfobetaine acrylamide) (pSBAA)-based nanocomposite hydrogels impregnated with germicidal silver nanoparticles (AgNPs) were synthesized and implemented for the treatment of infected chronic wounds. The zwitterionic hydrogels exhibited excellent non-sticky properties and had reinforced mechanical properties by the addition of hectorite nanoclay and poly(ethylene glycol)dimethacrylate as physical and chemical crosslinkers, respectively. In addition, AgNPs were grown within the intercalated clay/polymer structure by in situ free radical reduction, as confirmed by UV-vis spectroscopy and transmission electron microscopy (TEM). The silver-containing pSBAA nanocomposite hydrogels (pSBAA/Ag) exhibited germicidal properties against Gram-positive S. epidermidis and Gram-negative P. aeruginosa. The zwitterionic hydrogels show higher water content than 2-hydroxyethyl methacrylate (pHEMA) hydrogels, owing to the strong hydration via ionic solvation. The negligible cytotoxicity of pSBAA/Ag hydrogels was assessed with human fibroblasts by the MTT assay. Moreover, the zwitterionic hydrogels demonstrated excellent resistance to the adsorption of bovine serum albumin (BSA). To evaluate the feasibility of the hydrogels for clinical application as wound dressings, we created infected diabetic rat models and compared with commercial wound dressings. The results show that pSBAA/Ag hydrogels did not adhere to the newly formed tissue, and were readily removed from the wounds after treatment for 3 days. Moreover, the healing recovery was evaluated by visual observation of infected dorsal wounds on rats with induction of diabetes by streptozotocin. The finding indicates complete healing with the pSBAA/Ag hydrogels after 15 days, faster than other dressings. A histological examination also proved that the zwitterionic hydrogels facilitated epithelialization and collagen distribution in the infected diabetic wounds. Consequently, these novel non-sticky and antimicrobial zwitterionic nanocomposite hydrogels can have high potential for the treatment of infected chronic wounds.