Ultrasonographic findings of re-epithelialized skin after partial-thickness burns

Background:This study aimed to investigate the difference between ultrasonographic findings of normal skin and those of re-epithelialized skin after partial-thickness burns and to evaluate the relationship between these findings and clinical outcomes. Methods:This study retrospectively analysed the ultrasound images of re-epithelialized skin after partial-thickness burns and contralateral normal skin from January 2016 to December 2016. A total of 155 lesions from 148 patients were analysed with ultrasound images, and healing time was documented. The scar status of each lesion was evaluated through medical records and photographs. We analysed the difference in ultrasonographic findings between normal skin and re-epithelialized skin after partial-thickness burns and statistically analysed the relationship between healing time, scar status and ultrasonographic findings. Results: The re-epithelialized skin after partial-thickness burns was significantly thicker than the contralateral normal skin, and the echogenicity was significantly lower. The ultrasound images of the re-epithelialized skin after partial-thickness burns showed the characteristic findings of low-echogenic bands (LEB), and the proportion of LEB thickness is strongly correlated with healing time. In the multivariate analysis of scar status, only the proportion of LEB thickness was statistical y significant. Conclusion:In this study, we found that there were ultrasonographic differences between re-epithelialized skin after partial-thickness burns and normal skin and that an LEB of varying thickness was formed after re-epithelialization. The thickness of the LEB in re-epithelialized skin after partial-thickness burns increased with healing time and was related to scar status.

The Effect of Fibronectin on Re-epithelialization of Rabbits Cornea after Alkali Burn

The authors found experimentally that (1) fibronectin enhanced the healing of rabbit corneal epithelium after alkali burn and prevented the secondary breakdown; (2) it rapidly deposited on the denuded basement membrane to disappear as epithelial cells slided over, and (3) ultrastructurally, the neighbouring epithelial cells became flattened, with filopodia at the advancing edge, and extended to the wounded areas at 24 hours after the burn. However, the epithelial defects recurred 72 hours after the burn...

Evaluation of artificial tears on cornea epithelium healing

AIM： To observe the efficacy of different artificial eye drops on corneal epithelium healing in rabbit. METHODS： Thirty-five rabbits with 6 mm diameter central corneal epithelium removed were randomly assigned to six groups： 0.9% normal saline（NS） group, 0.1% hyaluronate（HA） group, 0.3% HA group, Tears Naturale Free？（TNF） group, 0.4% polyethylene glycol（PEG） group, 0.5% carboxymethyl cellulose（CMC） group and blank control group. Treatments were administered topically four times daily. Corneal epithelium healing was evaluated by the percentage reduction in wound area at 24, 36, 48, 60, and 72 h after removal of the corneal epithelium. Cornea re-epithelialization was also assessed by histological analysis and electron microscopy. RESULTS： All corneal wounds completely re-epithelialized in less than 72 h. The average re-epithelialization time was 47.61±4.25 h in the 0.3% HA group and 49.72±1.05 h in the 0.9% NS group, followed by 0.1% HA, TNF, 0.4% PEG, 0.5% CMC, and lastly by the control group. Compared to the control group, there were significant differences among 0.3% HA, 0.9% NS, PEG, and TNF（P〈0.05） groups. At the first 24 h, re-epithelialization at the 0.3% HA, TNF, and 0.9% NS treatment groups were significantly faster than the other groups. At 48 h post-wounding, corneal epithelium is nearly completing re-epithelialization at 0.3% HA and 0.9% NS treatment groups. Electron microscopy revealed that there were a large number of vacuoles in the cells of the 0.9% NS group at 72 h. CONCLUSION： Artificial tears promote corneal reepithelium varied in the efficacy. Obviously, all artificial eye drops better than blank group. In the process of corneal healing, corneal epithelium cells suffered from hypoxia caused by NS.

Total Particulate Matter and Wound Healing: An in vivo Study with Histological Insights

Objectives Wound healing in the skin is a multifarious orchestration of cellular processes and cigarette smoking may be a cause for delayed wound healing. The aim of this study was to investigate the plausible association between exposures of cigarette total particulate matter （TPM） and wound healing. Methods An in vivo wound healing model of mice was established for determination of assorted events of wound healing, dermal matrix regeneration, re-epithelialization, and neovascularization. A total of 72 adult mice, separated in eight groups, were exposed to TPM for 12 days. Results A highly considerable diminution in wound closure （P〈0.001） was pragmatic among all TPM-treated mice from day 6 to day 8 post-wounding. Histological investigations unveiled a noteworthy impede in the outcome of re-epithelialization, dermal matrix regeneration and maturation of collagen bundles among all TPM-exposed wounds. Delayed commencement of neovascularization was pragmatic among all TPM-treated mice, on day 12 post wounding. Abbot curve, angular spectrum, and other different parameters of 3D surface behavior of wounds revealed a very highly significant reduction （P〈0.001） in angiogenesis on days 6 and 8 post-wounding, which points that application of TPM instigates extensive delay in trigging the progression of angiogenesis, resulting in delayed onset of wound healing. Conclusion Our annotations validate the damaging effects of TPM on wound healing and excessive use of TPM may lead to the production of chronic wounds and oral ulcers.

Role of defensins in diabetic wound healing

The adverse consequences resulting from diabetes are often presented as severe complications.Diabetic wounds are one of the most commonly occurring complications in diabetes,and the control and treatment of this is costly.Due to a series of pathophysiological mechanisms,diabetic wounds remain in the inflammatory phase for a prolonged period of time,and face difficulty in entering the proliferative phase,thus leading to chronic non-healing wounds.The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management,however,standard wound treatment methods are still limited and therefore,more effective methods are required.In recent years,defensins have been found to play diverse roles in a variety of diseases;however,the molecular mechanisms underlying these activities are still largely unknown.Defensins can be constitutively or inductively produced in the skin,therefore,their local distribution is affected by the microenvironment of these diabetic wounds.Current evidence suggests that defensins are involved in the diabetic wound pathogenesis,and can potentially promote the early completion of each stage,thus making research on defensins a promising area for developing novel treatments for diabetic wounds.In this review,we describe the complex function of human defensins in the development of diabetic wounds,and suggest potential therapeutic benefits.

A Prospective, Within-Patient Controlled Study to Compare the Ability of the Non Adherent Drawtex®Hydroconductive Dressing to a Transparent Polyurethane Film Dressing (Standard of Care) on the Healing of Split-Thickness Skin Graft Donor Sites

Background: Dressing of split-thickness skin graft donor sites can be traumatic for the patient. The most advanced and expensive dressings have been compared to the most basic of dressings, with little or no consensus and an unpersuasive level of evidence. We aimed to determine the efficacy of the locally manufactured non-adherent, hydroconductive Drawtex? dressing and compare it to our current standard-of-care dressing, a thin transparent polyurethane film, in the healing of split-thickness donor sites. Methods: This prospective, within-patient controlled study included 27 adult participants, each with two split-thickness skin donor sites. The 54 donor site wounds were compared with regard to time to re-epithelialisation, perceived pain and healed wound quality. Results: By day 5, complete healing of donor site wounds, defined as >90% of epithelialized surface, was significantly higher in the hydroconductive dressing group compared to the polyurethane film group (22.2% and 3.7%, respectively;p < 0.0001). The hydroconductive dressing-treated donor site wounds were significantly less painful at 24-hours, 48-hours and 7-days post-operatively, and had fewer complications and superior wound healing quality. Conclusion: We have demonstrated that the relatively cheap and readily available dressing made locally in South Africa, Drawtex? is at least as safe, and potentially superior in wound healing, when compared to our current standard-of-care dressing.

Re-epithelialization resulted from prostate basal cells in canine prostatic urethra may represent the ideal healing method after two-micron laser resection of the prostate

The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate （TmLRP）. TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 （CK14）, CK5, CK18, synaptophysin （Syn）, chromogranin A （CgA）, uroplakin, transforming growth factor-β1 （TGF-β1）, and TGF-β type Ⅱ receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-β1 and TGF-β type Ⅱ receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.

Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study were to comprehensively examine the effectiveness,synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.Methods:Full-thickness wounds were made on the back of C57/BL6 mice.PRP or saline solution as a control was administered to the wound area.Wound healing rate,local inflammation,angiogenesis,re-epithelialization and collagen deposition were measured at days 3,5,7 and 14 after skin injury.The biological character of epidermal stem cells(ESCs),which reflect the potential for re-epithelialization,was further evaluated in vitro and in vivo.Results:PRP strongly improved skin wound healing,which was associated with regulation of local inflammation,enhancement of angiogenesis and re-epithelialization.PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β.An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1.Moreover,PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs,and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.Conclusion:PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization.However,the underlying regulatory mechanism needs to be investigated in the future.Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

Calcium silicate accelerates cutaneous wound healing with enhanced re-epithelialization through EGF/EGFR/ERK-mediated promotion of epidermal stem cell functions

Background:Human epidermal stem cells(hESCs)play an important role in re-epithelialization and thereby in facilitating wound healing,while an effective way to activate hESCs remains to be explored.Calcium silicate(CS)is a form of bioceramic that can alter cell behavior and promote tissue regeneration.Here,we have observed the effect of CS on hESCs and investigated its possible mechanism.Methods:Using a mouse full-thickness skin excision model,we explored the therapeutic effect of CS on wound healing and re-epithelialization.In vitro,hESCs were cultured with diluted CS ion extracts(CSIEs),and the proliferation,migration ability and stemness of hESCs were evaluated.The effects of CS on the epidermal growth factor(EGF),epidermal growth factor receptor(EGFR)and extracellular signal-related kinase(ERK)signaling pathway were also explored.Results:In vivo,CS accelerated wound healing and re-epithelialization.Immunohistochemistry demonstrated that CS upregulated cytokeratin 19 and integrinβ1 expression,indicating that CS improved hESCs stemness.In vitro studies confirmed that CS improved the biological function of hESCs.And the possible mechanism could be due to the activation of the EGF/EGFR/ERK signaling pathway.Conclusion:CS can promote re-epithelialization and improve the biological functions of hESCs via activating the EGF/EGFR/ERK signaling pathway.

Photodynamic therapy accelerates skin wound healing through promoting re-epithelialization

Background:Epidermal stem cells(EpSCs)that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis.Little is known about the effects of photochemical activation on EpSC differentiation,proliferation and migration during wound healing.The present study aimed to determine the effects of photodynamic therapy(PDT)on wound healing in vivo and in vitro.Methods:We created mouse full-thickness skin resection models and applied 5-aminolevulinic acid(ALA)for PDT to the wound beds.Wound healing was analysed by gross evaluation and haematoxylin–eosin staining in vivo.In cultured EpSCs,protein expression was measured using flow cytometry and immunohistochemistry.Cell migration was examined using a scratch model;apoptosis and differentiation were measured using flow cytometry.Results:PDT accelerated wound closure by enhancing EpSC differentiation,proliferation and migration,thereby promoting re-epithelialization and angiogenesis.PDT inhibited inflammatory infiltration and expression of proinflammatory cytokines,whereas the secretion of growth factors was greater than in other groups.The proportion of transient amplifying cells was significantly greater in vivo and in vitro in the PDT groups.EpSC migration was markedly enhanced after ALAinduced PDT.Conclusions:Topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization,promoting angiogenesis as well as modulating skin homeostasis.This work provides a preliminary theoretical foundation for the clinical administration of topical ALA-induced PDT in skin wound healing.

A curative-intent endoscopic surgery for postradiation nasopharyngeal necrosis in patients with nasopharyngeal carcinoma

Background:Postradiation nasopharyngeal necrosis(PRNN)is a severe complication after radiotherapy in patients with nasopharyngeal carcinoma(NPC),which can severely affect the quality of life and threaten the patient’s life.Only 13.4%-28.6%of patients can be cured by traditional repeated endoscopic debridement.Here,we introduced an innovative curative-intent endoscopic surgery for PRNN patients and evaluated its clinical efficacy.Methods:Clinical data of 72 PRNN patients who underwent radical endoscopic necrectomy,followed by reconstruc-tion using a posterior pedicle nasal septum and floor mucoperiosteum flap were analyzed to determine the efficacy of this surgery.The endpoints were complete re-epithelialization of the nasopharyngeal defect,relief of headache,and overall survival(OS).Results:All surgeries were successfully performed without any severe postoperative complications or death.The median value of numeric rating scales of pain decreased from 8 before surgery to 0 after surgery(P<0.001).Fifty-one patients(70.8%)achieved complete re-epithelialization of the nasopharyngeal defect.The number of cycles of radiotherapy(odds ratio[OR],7.254;95%confidence interval[CI]1.035-50.821;P=0.046),postoperative pathological result(OR,34.087;95%CI 3.168-366.746;P=0.004),and survival status of flap(OR,261.179;95%CI 17.176-3971.599;P<0.001)were independent risk factors of re-epithelialization of the nasopharyngeal defects.Postoperative patho-logical result(hazard ratio[HR],5.018;95%CI 1.970-12.782;P=0.001)was an independent prognostic factor for OS.The 2-year OS rate of the entire cohort was 77.9%.Conclusion:Curative-intent endoscopic necrectomy followed by construction using the posterior pedicle nasal septum and floor mucoperiosteum flap is a novel,safe,and effective treatment of PRNN in patients with NPC.

Tissue engineered esophagus by copper——small intestinal submucosa graft for esophageal repair in a canine model

Acellular porcine small intestinal submucosa(SIS)has been used for esophagoplasty with success in a canine model.However,it did not lead to complete epithelialization.For better reconstruction,a cellular component is required.Moreover,promotion of angiogenesis with copper has been widely recognized by basic research as well as clinical studies.In this study,we have evaluated the feasibility and effectiveness of combined Cu and SIS(SIS-Cu patch)for the esophageal repair using a canine model.Eighteen male beagle dogs were subjected to surgical resection to produce cervical esophageal defects(5 cm in length,180°in range).SIS with Cu(5 or 25μmol L 1copper)or without Cu was patched on the esophageal defects.Barium esophagram and histology exam were carried out to evaluate the effectiveness of the therapy.As shown,the SIS-Cu graft promoted re-epithelialization,re-vascularization and muscular regeneration.SIS-Cu patch is more effective than SIS alone for esophageal repair,and the SIS+25μmol L 1Cu group demonstrated additional advantages over the SIS+5μmol L 1Cu.

P311 promotes typeⅡtransforming growth factor-βreceptor mediated fibroblast activation and granulation tissue formation in wound healing

Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.

Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice

Background:Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury.However,the systematic and detailed evaluation of the scald burn injury,including second-degree deep scald(SDDS)and thirddegree scald(TDS),is still unclear.The present study aims to analyze the wound-healing speed,the formation of granulation tissue,and the healing quality after cutaneous damage.Methods:In order to assess SDDS and TDS,the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice.Furthermore,an excisional wound was administered on the dorsal surface in mice(Cut group).The wound-healing rate was first analyzed at days 0,3,5,7,15 and 27,with the Cut group as a control.Then,on the full-thickness wounds,hematoxylin and eosin(H&E)staining,Masson staining,Sirius red staining,Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization,the formation of granulation tissue,vascularization,inflammatory infiltration and the healing quality at different time points in the Cut,SDDS and TDS groups.Results:The presented data revealed that the wound-healing rate was higher in the Cut group,when compared with the SDDS and TDS groups.H&E staining showed that re-epithelialization,formation of granulation tissue and inflammatory infiltration were greater in the Cut group,when compared with the SDDS and TDS groups.Immunohistochemistry revealed that the number of CD31,vascular endothelial growth factor A,transforming growth factor-βandα-smooth muscle actin reached preferential peak in the Cut group,when compared with other groups.In addition,Masson staining,Sirius red staining,Victoria blue staining,Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III,reticular fibers,failure stress,Young’s modulus and failure length in the SDDS group were similar to those in the normal group,suggesting that healing quality was better in the SDDS group,when compared with the Cut and TDS groups.Conclusion:Overall,the investigators first administered a comprehensive analysis in the Cut,SDDS and TDS groups through in vivo experiments,which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.

A biological membrane-based novel excisional wound-splinting model in mice (With video)

Rodents have robust wound healing mechanism compared to other animal species.The major mechanisms of wound healing diff er between rodents and humans.In humans,wound healing primarily depends on re-epithelialization and granulation tissue(GT)formation,whereas wound contraction is more important during rodent wound closure.In this study,we described a novel excisional wound-splinting model in mice with a new biological membrane to imitate wound healing in humans.In this model,wound contraction can be eff ectually prevented,and the extent of re-epithelialization and the amount of granulation tissue can be determined easily.Furthermore,the harvested tissues can be analyzed with diff erent methods according to the research aim.In conclusion,we have developed a biological membrane-based,novel,excisional wound-splinting model in mice that has unique advantages for wound healing research compared with the conventional animal model.