Enhanced Diabetic Rat Wound Healing by Platelet-Rich Plasma Adhesion Zwitterionic Hydrogel.

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.

Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability.

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, 1HNMR 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 ß1 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.

A Very Rare Case of Necrotizing Fasciitis Caused by Metallosis.

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.

Clinical Application of the Peroneal Artery Perforator Flap for Reconstruction of Lateral Malleolus Defects.

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 cm2. 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.

ENERGI-F703 gel, as a new topical treatment for diabetic foot and leg ulcers: A multicenter, randomized, double-blind, phase II trial.

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 15th, 2017 to December 26th, 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.

Planar-/Curvilinear-Bioprinted Tri-Cell-Laden Hydrogel for Healing Irregular Chronic Wounds.

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.

Biomimetic Strain-Stiffening in Chitosan Self-Healing Hydrogels.

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.

Simple and Efficient Pressure Ulcer Reconstruction via Primary Closure Combined with Closed-Incision Negative Pressure Wound Therapy (CiNPWT)-Experience of a Single Surgeon.

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 cm2), 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.

An In Vitro Study of the Effects of Mechanical and Enzymatic Isolation of Stromal Vascular Fraction on Wound Healing.

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 α5ß1) 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.

Is 3-Dimensional Scanning Really Helpful in Implant-Based Breast Reconstruction?: A Prospective Study.

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.

Severe burn injury from the common Asian practice of heat application in patients with diabetic neuropathy.

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.

Ranking hospitals' burn care capacity using cluster analysis on open government data.

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.

Negative-pressure wound therapy combined with artificial dermis (Terudermis) followed by split-thickness skin graft might be an effective treatment option for wounds exposing tendon and bone: A retrospective observation study.

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 ±â€Š7.14 days. In separately, the survival time of artificial dermis had no statistically difference in chronic wound group (13.64 ±â€Š7.53 vs 12.60 ±â€Š5.86. P = .943), but had significant statistical difference in acute trauma group (12.45 ±â€Š6.44 days vs 23.33 ±â€Š4.04 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.

Beneficial Effects of Astragaloside IV-Treated and 3-Dimensional-Cultured Endothelial Progenitor Cells on Angiogenesis and Wound Healing.

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.

Negative Pressure Wound Therapy in Conjunction With Artificial Dermis for Burned Hand Reconstruction.

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.

Clinical Performance of Hydrogel-based Dressing in Facial Burn Wounds: A Retrospective Observational Study.

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.

Cryogel/hydrogel biomaterials and acupuncture combined to promote diabetic skin wound healing through immunomodulation.

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 TGFß-1, as well as the down-regulation of proinflammatory cytokines TNF-α and IL-1ß, 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.

Characterization of intracellular buffering power in human induced pluripotent stem cells and the loss of pluripotency is delayed by acidic stimulation and increase of NHE1 activity.

The homeostasis of intracellular pH (pHi ) affects many cellular functions. Our previous study has established a functional and molecular model of the active pHi regulators in human induced pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pHi buffering power (ß) and to investigate the effects of extracellular pH and Na+ -H+ exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pHi 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 (ßtot ), intrinsic (ßi ), and CO2 -dependent ( ßCO2 ) buffering power all increased while pHi increased; (b) during the spontaneous differentiation for 4 days, the ß values of ßtot and ßCO2 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 ß during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs.

Necrotizing Fasciitis Caused by Aeromonas hydrophila With Catastrophic Progression.

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.

A Review of Skin Banking Guidelines and Standards Worldwide: Towards the Harmonization of Guidelines for Skin Banking in Therapeutic Applications for the Regions under the Asia Pacific Burn Association (APBA).

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.