Epithelial-mesenchymal transition in the formation of hypertrophic scars and keloids.

Abnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients. Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial-mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids.

GDC-0084 inhibits cutaneous squamous cell carcinoma cell growth.

GDC-0084 is a novel and potent small-molecule PI3K-mTOR dual inhibitor. The present study examined its potential activity in cutaneous squamous cell carcinoma (cSCC) cells. Our results show that GDC-0084 treatment at nanomole concentrations potently inhibited survival and proliferation of established (A431, SCC-13 and SCL-1 lines) and primary human cSCC cells. GDC-0084 induced apoptosis activation and cell cycle arrest in the cSCC cells. It was more efficient than other known PI3K-Akt-mTOR inhibitors in killing cSCC cells, but was non-cytotoxic to the normal human skin fibroblasts/keratinocytes. In A431 cells and primary cSCC cells, GDC-0084 blocked phosphorylation of key PI3K-Akt-mTOR components, including p85, Akt, S6K1 and S6. GDC-0084 also inhibited DNA-PKcs activation in cSCC cells. Significantly, restoring DNA-PKcs activation by a constitutively active-DNA-PKcs (S2056D) partially inhibited GDC-0084-induced cell death and apoptosis in A431 cells. In vivo, GDC-0084 daily gavage potently inhibited A431 xenograft tumor growth in mice. In GDC-0084-treated tumor tissues PI3K-Akt-mTOR and DNA-PKcs activation were significantly inhibited. In summary, GDC-0084 inhibits human cSCC cell growth in vitro and in vivo through blocking PI3K-Akt-mTOR and DNA-PKcs signalings.

Effectiveness and Safety of Compound Polymyxin B Ointment in Treatment of Burn Wounds: A Meta-analysis.

Burn injuries represent a global public health concern. The guidelines for burn care mention that the treatment of burn injuries depends on the type of burn injury, depth of tissue, area of wounds, and site on the body. At present, several topical antimicrobial agents are used in the treatment of burn wounds as a first choice. This study aims to investigate the effectiveness of the compound polymyxin B topical agents for the treatment of burn wounds. PubMed, Web of Science, ProQuest, and China National Knowledge Infrastructure databases were searched for articles published until January 2021. The studies that conducted clinical trials comparing compound polymyxin B ointment with other treatment reagents for burn wound treatment were included. A total of three outcomes, which were investigator-assessed clinical response, including mortality, bacterial counts, efficacy and safety were included for analysis in this study. In total, 12 randomized controlled trials, 1 clinical trial, 2 prospective studies, and 1 retrospective study were extracted. The result of mortality showed no significant difference (risk ratio [RR]: 0.70, 95% CI: 0.21-2.31, P = .56); wound healing revealed an RR of 1.59 (95% CI: 1.40-1.81, P < .001); time to heal revealed a mean difference of -5.09 (95% CI: -6.31 to -3.86) days (P < .001); scar incidence was not significantly lower in the treatment group (RR: 0.70, 95% CI: 0.38-1.30, P = .26); and adverse event incidence was significantly lower in the treatment group (RR: 0.26, 95% CI: 0.09-0.72, P < .01). The compound polymyxin B ointment shows the effectiveness of increase in the wound healing and accelerates the time of healing with fewer adverse effects.

A keratin/chitosan sponge with excellent hemostatic performance for uncontrolled bleeding.

Uncontrolled bleeding leads to a higher fatality rate in the situation of surgery, traffic accidents and warfare. Traditional hemostatic materials such as bandages are not ideal for uncontrolled or incompressible bleeding. Therefore, it is of great significance to develop a new medical biomaterial with excellent rapid hemostatic effect. Keratin is a natural, biocompatible and biodegradable protein which contains amino acid sequences that induce cell adhesion. As a potential biomedical material, keratin has been developed and paid attention in tissue engineering fields such as promoting wound healing and nerve repair. Herein, a keratin/chitosan (K/C) sponge was prepared to achieve rapid hemostasis. The characterizations of K/C sponge were investigated, including SEM, TGA, liquid absorption and porosity, showing that the high porosity up to 90.12 ± 2.17 % resulted in an excellent blood absorption. The cytotoxicity test and implantation experiment proved that the K/C sponge was biocompatible and biodegradable. Moreover, the prepared K/C sponge showed better hemostatic performance than chitosan sponge (CS) and the commercially available gelatin sponge in both rat tail amputation and liver trauma bleeding models. Further experiments showed that K/C sponge plays a hemostatic role through the endogenous coagulation pathway, thus shortening the activated partial thromboplastin time (APTT) effectively. Therefore, this study provided a K/C sponge which can be served as a promising biomedical hemostatic material.

Long-term medical treatment of patients with severe burns at exposed sites.

BACKGROUND: Body parts such as the face and hands are highly exposed during daily life and burns may accumulate in these areas. In addition, residual wounds, scar hyperplasia and contracture often exist in the late stage of a deep burn in these areas, which may affect patients' appearance, movements, and mental health. However, inadequate attention has been paid to this issue which can result in problems, such as difficulty in healing, possibility of carcinoma, chronic pain and a heavy mental burden. AIM: To investigate the long-term medical treatment of patients with severe burns at exposed sites following a mass burn casualty event. METHODS: A retrospective analysis of 13 patients with severe burns at exposed sites was performed to determine their respective long-term medical treatment. A combined wound dressing scheme consisting of traditional Chinese and Western medicine was introduced to repair residual wounds. Active and passive functional exercises with massage, Chinese herbal baths and compression fixation were proposed to ameliorate the condition of the hands. A combination of physical, chemical and photoelectrical measures was adopted for anti-scar treatment. A psychological intervention and recovery guide was provided which corresponded to the patients' psychological status. RESULTS: Compared to patients who did not simultaneously receive the same treatment, patients who underwent systematic treatment recovered with a lower wound infection rate (P < 0.05), a shorter healing time (13.6 ± 3.2 d) compared with (19.1 ± 3.5 d) and more bearable pain during wound dressing at three days, one week and two weeks after a Chinese herbal bath (P < 0.05). Satisfactory results were achieved with regard to restored function of patients' joints and blood supply to nerve endings, closure of the eyelids and the size of mouth opening tended to be normal, and only 7.1% of patients were diagnosed with severe scar hyperplasia and contracture deformity compared with 30.7% in the control group. In addition, the color, thickness, vascular distribution and softness score of the scars improved (P < 0.01), and the effects of the psychological intervention was remarkable as shown by the Self-Rating Anxiety Scale and Self-Rating Depression Scale. CONCLUSION: A better prognosis can be achieved in patients in the late stage of a burn with active residual wound repair, limb functional exercise, anti-scar and psychological rehabilitation.

Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation.

BACKGROUND: Hypertrophic scar (HS) is characterized by the increased proliferation and decreased apoptosis of myofibroblasts. Myofibroblasts, the main effector cells for dermal fibrosis, develop from normal fibroblasts. Thus, the stimulation of myofibroblast apoptosis is a possible treatment for HS. We aimed to explore that whether over-activated myofibroblasts can be targeted for apoptosis by anticancer drug elesclomol. METHODS: 4',6-diamidino-2-phenylindole staining, flow cytometry, western blotting, collagen gel contraction and immunofluorescence assays were applied to demonstrate the proapoptotic effect of elesclomol in scar derived myofibroblasts and TGF-ß1 induced myofibroblasts. The therapeutic potential of elesclomol was investigated by establishing rabbit ear hypertrophic scar models. FINDINGS: Both 4',6-diamidino-2-phenylindole staining and flow cytometry indicated that elesclomol targets myofibroblasts in vitro. Collagen gel contraction assay showed that elesclomol inhibited myofibroblast contractility. Flow cytometry and western blot analysis revealed that elesclomol resulted in excessive intracellular levels of reactive oxygen species(ROS), and caspase-3 and cytochrome c proteins. Moreover, compared with the control group, the elesclomol group had a significantly lower scar elevation index in vivo. Immunofluorescence assays for TUNEL and α-smooth muscle actin indicated that elesclomol treatment increased the number of apoptotic myofibroblasts. INTERPRETATION: The above results indicate that elesclomol exerted a significant inhibitory effect on HS formation via targeted myofibroblast apoptosis associated with increased oxidative stress. Thus, elesclomol is a promising candidate drug for the treatment of myofibroblast-related diseases such as HS.

Emerging Role of IL-10 in Hypertrophic Scars.

Hypertrophic scars (HS) arise from traumatic or surgical injuries and the subsequent abnormal wound healing, which is characterized by continuous and histologically localized inflammation. Therefore, inhibiting local inflammation is an effective method of treating HS. Recent insight into the role of interleukin-10 (IL-10), an important anti-inflammatory cytokine, in fibrosis has increased our understanding of the pathophysiology of HS and has suggested new therapeutic targets. This review summarizes the recent progress in elucidating the role of IL-10 in the formation of HS and its therapeutic potential based on current research. This knowledge will enhance our understanding of the role of IL-10 in scar formation and shed new light on the regulation and potential treatment of HS.

Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation.

Hypertrophic scars are pathological scars that result from abnormal responses to trauma, and could cause serious functional and cosmetic disability. To date, no optimal treatment method has been established. A variety of cell types are involved in hypertrophic scar formation after wound healing, but the underlying molecular mechanisms and cellular origins of hypertrophic scars are not fully understood. Macrophages are major effector cells in the immune response after tissue injury that orchestrates the process of wound healing. Depending on the local microenvironment, macrophages undergo marked phenotypic and functional changes at different stages during scar pathogenesis. This review intends to summarize the direct and indirect roles of macrophages during hypertrophic scar formation. The in vivo depletion of macrophages or blocking their signaling reduces scar formation in experimental models, thereby establishing macrophages as positive regulatory cells in the skin scar formation. In the future, a significant amount of attention should be given to molecular and cellular mechanisms that cause the phenotypic switch of wound macrophages, which may provide novel therapeutic targets for hypertrophic scars.

Fabrication of tough poly(ethylene glycol)/collagen double network hydrogels for tissue engineering.

In this study, a series of poly(ethylene glycol)/collagen (PEG/Col) double network (DN) hydrogel is fabricated from PEG and Col. Results of the compressive strength test indicate that the strength and toughness of these DN hydrogels are significantly enhanced. The fracture strength of PEG/Col DN hydrogels increases by 9- to 12-fold compared with that of PEG single network (SN) hydrogel, and by 36- to 48-fold compared with that of Col SN hydrogel. Taking advantage of both PEG and Col building blocks, the PEG/Col DN hydrogels possess a strengthened skeleton. Moreover, the water-storage capability and favorable biocompatibility of Col are effectively maintained. Given that the DN hydrogels can provide the appropriate environment for the adhesion, growth, and proliferation of MC3T3-E1 cells, PEG/Col DN hydrogels have potential as a load-bearing tissue repair material. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 192-200, 2018.

[Clinical application of Meek micrograft technique].

OBJECTIVE: To explore the clinical application of the transplantation of the Meek autograft. METHODS: Meek autografts were transplanted on the full-thickness wounds of 10 patients, including 9 cases of burn and 1 case of necrofascitis, with the area of 8.6% (2% - 28%) of the total body surface, and the average of the area was. Meek skin graft was placed on the wounds immediately after escharectomy (in 4 cases), 4 - 16 days after tangential excision (in 4 cases), or on the clean wound granulation 35 - 45 days after the injury (in 2 cases). 108 pieces of extending gauze of different rates were used. As comparison, Stamp-like grafts, micrografts, or net-like graft were used in different places of the same bodies in 5, 4, and 1 case respectively. RESULTS: The operation time of Meek micrograft technique was 9 - 60 minutes. The survival rate of the Meek graft was 93% (100% in 8 cases for, 80% in 1 case, and 50% in 1 case). The operation time of the other operation techniques was 30 - 240 minutes. The average survival rate of the other operation techniques was 86% (100% in 2 cases, 90% - 98% in 4 cases, 80% in 3 cases, and 50% in 1 case). CONCLUSION: Meek autograft is suitable for all of the full-thickness wound except bone-exposure wound, including the wound of major burns. This technique uses less skin to repair the wound and the time for epithelization is shorter than that of the traditional methods. The staff and time needed for the operation are less. The outcome is good and the healed wound is fine-looking.

[Effect of recombinant human granulocyte-macrophage colony stimulating factor on wound healing in patients with deep partial thickness burn].

OBJECTIVE: To evaluate the efficacy and safety of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) hydrogel in wound healing in patients with deep partial thickness burn. METHODS: The study was a multicenter, randomized, double-blind, placebo-controlled parallel clinical trial. Three hundred and twenty-one patients (302 cases finally fulfilled the protocol) with deep partial thickness burn were divided into A group (n = 200, with treatment of rhGM-CSF hydrogel, 100 microg/10 g/100 cm2/d), C group (n = 102,with treatment of placebo). Side-effect, systemic condition, wound healing time, wound healing rate, and total effective rate at different time points were observed. RESULTS: There were no obvious differences in vital signs, wound secretion, wound edge reaction, blood and urine routine, liver and kidney function between two groups (P > 0.05). No side-effect was observed. The median wound healing time was 17 days in A group, which was obviously shorter than that in C group (20 days, P < 0.01). The mean wound healing rate in A group was 24.5%, 70.5%, 95.3%, 99.6% respectively on 8th, 14th, 20th, 28th day after treatment, which were obviously higher than that in C group (15.1%, 51.4%, 84.6%, 97.1%, respectively, P < 0.01). The total effective rates in A group on 8th, 14th, 20th day after treatment were also higher than that in C group (P < 0.01). CONCLUSION: rhGM-CSF hydrogel can significantly accelerate wound healing in patients with deep partial thickness burn with certain safety.

[Multi-center clinical study of the effect of silver nitrate ointment on the partial-thickness burn wounds].

OBJECTIVE: To evaluate the therapeutic effect of silver nitrate ointment on partial-thickness burn wounds, and observe its side-effects. METHODS: Multi-center, randomized, positive drug paralleled self-controlled trial was carried out. Eighty patients with superficial partial-thickness burns, and 40 with deep-partial thickness burns were randomized into AgNO3 group and SD-Ag group according to drug topically applied to the wounds. The wound healing time, wound healing rate and bacterial culture of the wound, the effect and safety of the drug, as well as drug irritation to the wounds were studied in these two groups. RESULTS: For the patients with superficial partial-thickness burn wounds, the wound healing time in silver nitrate group was (9.5 +/- 2.7) days, which was obviously shorter than that in SD-Ag group [(10.8 +/- 3.4) days, P <0.01]. The wound healing rate in silver nitrate group on 7 post-burn day ( PBD) was (77.9 +/- 20.5)%, which was obviously higher than that in SD-Ag group [(67.3 +/- 22.6) %, P < 0.01]. For those with deep-partial thickness burn wounds, the wound healing time in silver nitrate group was (21.5 +/- 4.8) days, which was evidently shorter than that in SD-Ag group [(23.3 +/- 6.4) days, P <0.01]. The wound healing rate in silver nitrate group on 20 PBD was (86.6 +/- 15.9)%, which was evidently higher than that in SD-Ag group [(78.5 +/- 17.7)%, P < 0.01]. Silver nitrate ointment has the same antibacterial effect as 1% SD-Ag cream, but it was less painful when applied to the open wounds. CONCLUSION: Silver nitrate ointment is an effective and safe medicament for the clinical management of partial-thickness burn wounds.