Acute and chronic wound fluids influence keratinocyte function differently

Wound healing requires a proper functioning of keratinocytes that migrate, proliferate and lead to a competent wound closure. Impaired wound healing might be due to a disturbed keratinocyte function caused by the wound environment. Basically, chronic wound fluid (CWF) differs from acute wound fluid (AWF). The aim of this study was to analyse the effects of AWF and CWF on keratinocyte function. We therefore investigated keratinocyte migration and proliferation under the influence of AWF and CWF using MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] test and scratch assay. We further measured the gene expression by qRT‐PCR regarding growth factors and matrixmetalloproteinases (MMPs) involved in regeneration processes. AWF had a positive impact on keratinocyte proliferation over time, whereas CWF had an anti‐proliferative effect. Keratinocyte migration was significantly impaired by CWF in contrast to an undisturbed wound closure under the influence of AWF. MMP‐9 expression was strongly upregulated by CWF compared with AWF. Keratinocyte function was significantly impaired by CWF. An excessive induction of MMP‐9 by CWF might lead to a permanent degradation of extracellular matrix and thereby prevent wounds from healing.     

Adipose‐derived stem cells and keratinocytes in a chronic wound cell culture model: the role of hydroxyectoine

Chronic wounds represent a major socio‐economic problem in developed countries today. Wound healing is a complex biological process. It requires a well‐orchestrated interaction of mediators, resident cells and infiltrating cells. In this context, mesenchymal stem cells and keratinocytes play a crucial role in tissue regeneration. In chronic wounds these processes are disturbed and cell viability is reduced. Hydroxyectoine (HyEc) is a membrane protecting osmolyte with protein and macromolecule stabilising properties. Adipose‐derived stem cells (ASC) and keratinocytes were cultured with chronic wound fluid (CWF) and treated with HyEc. Proliferation was investigated using MTT test and migration was examined with transwell‐migration assay and scratch assay. Gene expression changes of basic fibroblast growth factor (b‐FGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases‐2 (MMP‐2) and MMP‐9 were analysed by quantitative real‐time polymerase chain reaction (qRT‐PCR). CWF significantly inhibited proliferation and migration of keratinocytes. Addition of HyEc did not affect these results. Proliferation capacity of ASC was not influenced by CWF whereas migration was significantly enhanced. HyEc significantly reduced ASC migration. Expression of b‐FGF, VEGF, MMP‐2 and MMP‐9 in ASC, and b‐FGF, VEGF and MMP‐9 in keratinocytes was strongly induced by chronic wound fluid. HyEc enhanced CWF induced gene expression of VEGF in ASC and MMP‐9 in keratinocytes. CWF negatively impaired keratinocyte function, which was not influenced by HyEc. ASC migration was stimulated by CWF, whereas HyEc significantly inhibited migration of ASC. CWF induced gene expression of VEGF in ASC and MMP‐9 in keratinocytes was enhanced by HyEc, which might partly be explained by an RNA stabilising effect of HyEc.     

The role of SDF‐1 in homing of human adipose‐derived stem cells

One of the putative pathophysiological mechanisms of chronic wounds is a disturbed homing of stem cells. In this project, the stromal cell‐derived factor 1 (SDF‐1)/C‐X‐C chemokine receptor (CXCR) 4 and SDF‐1/CXCR7 pathway were focused in human adipose‐derived stem cells (ASCs). ASCs were incubated with acute (AWF) or chronic wound fluid (CWF) to analyze their effects by quantitative real‐time polymerase chain reaction (SDF‐1, CXCR4, CXCR7, TIMP3), enzyme‐linked immunosorbent assay (SDF‐1 in WFs and supernatant), and transwell migration assay with/without antagonization. Whereas SDF‐1 amounted 73.5 pg/mL in AWF, it could not be detected in CWF. Incubation with AWF led to a significant enhancement (129.7 pg/mL vs. 95.5 pg/mL), whereas CWF resulted in a significant reduction (30 pg/mL vs. 95.5 pg/mL) of SDF‐1 in ASC supernatant. The SDF‐1 receptor CXCR7 was detected on ASCs. AWF but not CWF significantly induced ASC migration, which was inhibited by CXCR4 and CXCR7 antagonists. Expressions of SDF‐1, CXCR4, and CXCR7 were significantly stimulated by AWF while TIMP3 expression was reduced. In conclusion, an uncontrolled inflammation in the chronic wound environment, indicated by a reduced SDF‐1 expression, resulted in a decreased ASC migration. A disturbed SDF‐1/CXCR4 as well as SDF‐1/CXCR7 pathway seems to play an important role in the impaired healing of chronic wounds.     

Efficacy and cost‐effectiveness of octenidine wound gel in the treatment of chronic venous leg ulcers in comparison to modern wound dressings

The aim of this study was to determine the efficacy, safety and cost‐effectiveness of an octenidine‐based wound gel in the treatment of chronic venous leg ulcers. For this purpose, 49 wounds were treated with either modern wound‐phase‐adapted dressings alone (treatment arm 1; n = 17), octenidine wound gel plus modern wound‐phase‐adapted dressings (treatment arm 2; n = 17) or octenidine wound gel alone (treatment arm 3; n = 15). During the study period of 42 days with dressing changes every 3–5 days, wound healing characteristics and treatment costs of different dressings were analysed. Wound size reduction was significantly better (P = 0·028) in both octenidine wound gel treatment arms compared to modern dressings alone with total reductions of 14·6%, 64·1% and 96·2% in treatment arms 1–3. Early wound healing was merely observed under octenidine wound gel treatment (n = 9), whereby lowest treatment costs were generated by octenidine wound gel alone (€20·34/dressing change). As a result, the octenidine wound gel is cost‐effective and well suitable for the treatment of chronic venous leg ulcers, considering both safety and promotion of wound healing.     

Low flow oxygenation of full‐excisional skin wounds on diabetic mice improves wound healing by accelerating wound closure and reepithelialization

Oxygen‐based therapies have proven effective in treating chronic and difficult‐to‐heal skin wounds, but the current therapeutic approaches suffer from major limitations and they do not allow for continuous wound treatment. Here we examined whether the continuous treatment of wounds with pure oxygen at low flow rates accelerates wound closure and improves wound healing in a murine model of diabetic skin wounds. Two full‐excisional dorsal skin wounds were generated on 15‐week‐old diabetic db/db mice and treated for 10 weeks continuously with pure oxygen (>99·9%) at low flow rates (3 ml/h). After 6 days, oxygen treatment resulted in a mean reduction of the original wound size by 60·2% as compared with only 45·2% in wounds on control mice that did not receive pure oxygen.(P = 0·022). After 10 days, oxygen‐treated wounds were 83·1% closed compared with 71·2% in wounds on control mice. While reepithelialisation was complete after 10 days in over 57% of wounds receiving low flow oxygen treatment, significant epithelial gaps remained in 75% wounds from mice that did not receive oxygen. Continuous low flow oxygenation significantly improves healing of diabetic skin wounds in mice and may therefore be an effective treatment for chronic cutaneous and possibly other slow‐healing wounds in diabetic patients.     

Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We developed a model to detect which factors can predict (prolonged) healing of complex acute wounds in patients treated in a large wound expertise centre (WEC). Using Cox and linear regression analyses, we determined which patient‐ and wound‐related characteristics best predict time to complete wound healing and derived a prediction formula to estimate how long this may take. We selected 563 patients with acute wounds, documented in the WEC registry between 2007 and 2012. Wounds had existed for a median of 19 days (range 6–46 days). The majority of these were located on the leg (52%). Five significant independent predictors of prolonged wound healing were identified: wound location on the trunk [hazard ratio (HR) 0·565, 95% confidence interval (CI) 0·405–0·788; P = 0·001], wound infection (HR 0·728, 95% CI 0·534–0·991; P = 0·044), wound size (HR 0·993, 95% CI 0·988–0·997; P = 0·001), wound duration (HR 0·998, 95% CI 0·996–0·999; P = 0·005) and patient's age (HR 1·009, 95% CI 1·001–1·018; P = 0·020), but not diabetes. Awareness of the five factors predicting the healing of complex acute wounds, particularly wound infection and location on the trunk, may help caregivers to predict wound healing time and to detect, refer and focus on patients who need additional attention.     

Potential of Oncostatin M to accelerate diabetic wound healing

Oncostatin M (OSM) is a multifunctional cytokine found in a variety of pathologic conditions, which leads to excessive collagen deposition. Current studies demonstrate that OSM is also a mitogen for fibroblasts and has an anti‐inflammatory action. It was therefore hypothesised that OSM may play an important role in healing of chronic wounds that usually involve decreased fibroblast function and persist in the inflammatory stage for a long time. In a previous in vitro study, the authors showed that OSM increased wound healing activities of diabetic dermal fibroblasts. However, wound healing in vivo is a complex process involving multiple factors. Thus, the purpose of this study was to evaluate the effect of OSM on diabetic wound healing in vivo. Five diabetic mice were used in this study. Four full‐thickness round wounds were created on the back of each mouse (total 20 wounds). OSM was applied on the two left‐side wounds (n = 10) and phosphate‐buffered saline was applied on the two right‐side wounds (n = 10). After 10 days, unhealed wound areas of the OSM and control groups were compared using the stereoimage optical topometer system. Also, epithelialisation, wound contraction and reduction in wound volume in each group were compared. The OSM‐treated group showed superior results in all of the tested parameters. In particular, the unhealed wound area and the reduction in wound volume demonstrated statistically significant differences (P < 0·05). The results of this study indicate that topical application of OSM may have the potential to accelerate healing of diabetic wounds.     

A prospective,multicentre study on the use of epidermal grafts to optimise outpatient wound management

Current wound management through the use of a split‐thickness skin graft often requires hospital admission, a period of immobility, attentive donor site wound care and pain management. This study evaluates the feasibility of using a novel epidermal graft‐harvesting device (CelluTome) that allows pain‐free epidermal skin grafting in the outpatient clinic setting. A prospective series of 35 patients was performed in 2 centres, involving 10 acute and 25 chronic wounds. All patients were subjected to epidermal grafting in the outpatient specialist clinic, without the use of anaesthesia, and allowed to return home after the procedure. Completely healed wounds were noted in 22 patients (62·9%). The overall mean time for 50% and 100% reduction in wound size was 3·31 ± 2·33 and 5·91 ± 3·48 weeks, respectively. There was no significant difference in healing times between the acute and chronic wounds (50% reduction in wound size; acute 2·20 ± 0·91 weeks versus chronic 3·73 ± 2·63 weeks, P = 0·171. Hundred percent reduction in wound size; acute 4·80 ± 1·61 weeks versus chronic 6·83 ± 4·47 weeks, P = 0·183). The mean time for donor site healing was 5·49 ± 1·48 days. The mean pain score during graft harvest was 1·42 ± 0·95, and the donor site Vancouver Scar Scale was 0 for all cases at 6 weeks. This automated device offers autologous skin harvesting in the outpatient setting with minimal or no pain and a scar free donor site, equally benefiting both the acute and chronic wounds. It has the potential to save NHS resources by eliminating the need for theatre space and a hospital bed while at the same time benefiting patient care.     

Reduction in wound healing times,cost of consumables and number of visits treated through the implementation of an electronic wound care system in rural Australia

Globally, wound care costs the health care system 2–3% of the total expenditure on health, which equates to several billion dollars annually. To date, there are little data on the cost and healing rates of various wounds. This has been partly because of the difficulty in tracking wound management as the majority of wound care data has been focused on retrospective data from hospitals, general practice clinics and aged care facilities. This study reports on wound healing and cost of wounds collected from a larger project using the mobile wound care (MWC) electronic documentation system, which has been described elsewhere. The study involved 2350 clients from four health service districts in the Gippsland region in rural Australia who received treatments as part of the MWC research project (2010–2012), with a total of 3726 wounds identified (so an average of 1·6 wounds per client). By the end of the data collection period, 81% of these wounds had healed. A significant drop in healing time, cost of consumables and number of visits was found across the 3‐year period.     

Wound dressing components degrade proteins detrimental to wound healing

Excessive levels of matrix metalloproteinases (MMPs) are present in chronic wounds preventing wound closure. Reducing detrimental components may be key in healing chronic wounds. Elta Protease-containing wound dressings have been observed clinically to resolve inflammation and appear to aid healing in acute and chronic recalcitrant wounds. To investigate possible mechanisms of action, in vitro tests, zymography, collagenase assays and enzyme-linked immunosorbent assays (ELISAs), were performed to evaluate the effect of the dressing proteases on detrimental and beneficial wound healing components such as MMPs, Tissue Inhibitor of Matrix Metalloproteinases (TIMPs), cytokines and growth factors. Standards of pro- and active MMP-2, MMP-9 and chronic wound fluid (CWF) were prepared. Degradation of target proteins was enhanced by increased Elta Protease concentration, temperature and incubation time. Incubation with serial dilutions of the Elta Proteases resulted in nearly complete degradation of all MMP standards. After a 30-minute incubation, twofold diluted Elta Proteases degraded >90% of the gelatinases in CWF. ELISAs showed that Elta Proteases effectively degraded MMP-9 and tumour necrosis factor (TNF-alpha). In contrast, Platelet Derived Growth Factor (PDGF) and interleukin 1 beta were resistant to degradation by Elta Proteases. These results suggest that Elta Protease dressings appear to deactivate detrimental components in CWF, which may reduce wound bed contact with harmful proteins.     

Incisional negative pressure wound therapy after hemiarthroplasty for femoral neck fractures – reduction of wound complications

The aim of the study was to evaluate the use of incisional negative pressure wound therapy (iNPWT) in wound healing after femoral neck fracture (FNF) treated with hip hemiarthroplasty (HA) and its influence on postoperative seromas, wound secretion, as well as time and material consumption for dressing changes. The study is a prospective randomised evaluation of iNPWT in patients with large surgical wounds after FNF. Patients were randomised either to be treated by iNPWT (group A) or a standard wound dressing (group B). Follow‐up included ultrasound measurements of seroma volumes on postoperative days 5 and 10, duration of wound secretion, and time and material spent for wound dressing changes. For comparison of the means, we used the t‐test for independent samples, P > 0·05 was considered significant. There were 21 patients randomised in this study. Group A (11 patients, 81·6 ± 5·2 years of age) developed a seroma of 0·257 ± 0·75 cm³ after 5 days and had a secretion of 0·9 ± 1·0 days, and the total time for dressing changes was 14·8 ± 3·9 minutes, whereas group B (ten patients, 82·6 ± 8·6 years of age) developed a seroma of 3·995 ± 5·01 cm³ after 5 days and had a secretion of 4·3 ± 2·45 days, and the total time for dressing changes was 42·9 ± 11·0 minutes. All mentioned differences were significant. iNPWT has been used on many different types of traumatic and non‐traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas, reduction of total wound secretion days and reduction of needed time for dressing changes.     

Relationship between maceration and wound healing on diabetic foot ulcers in Indonesia: a prospective study

The aim of this study was to clarify the relationship between maceration and wound healing. A prospective longitudinal design was used in this study. The wound condition determined the type of dressings used and the dressing change frequency. A total of 62 participants with diabetic foot ulcers (70 wounds) were divided into two groups: non‐macerated (n = 52) and macerated wounds (n = 18). Each group was evaluated weekly using the Bates–Jensen Wound Assessment Tool, with follow‐ups until week 4. The Mann–Whitney U test showed that the changes in the wound area in week 1 were faster in the non‐macerated group than the macerated group (P = 0·02). The Pearson correlation analysis showed a moderate correlation between maceration and wound healing from enrolment until week 4 (P = 0·002). After week 4, the Kaplan–Meier analysis showed that the non‐macerated wounds healed significantly faster than the macerated wounds (log‐rank test = 19·378, P = 0·000). The Cox regression analysis confirmed that maceration was a significant and independent predictor of wound healing in this study (adjusted hazard ratio, 0·324; 95% CI, 0·131–0·799; P = 0·014). The results of this study demonstrated that there is a relationship between maceration and wound healing. Changes in the wound area can help predict the healing of wounds with maceration in clinical settings.     

A parallel open-label trial to evaluate microbial cellulose wound dressing in the treatment of diabetic foot ulcers

The purpose of this study was to compare the rate of wound healing in diabetic foot ulcers (DFU) using either a microbial cellulose (MC) wound dressing or Xeroform? Petrolatum gauze. In a parallel, open‐label trial in which the primary outcome was the rate of wound healing and the time to wound closure, 15 ulcers in type II diabetic patients received an MC dressing. Wounds in 19 control patients with type II diabetes were treated with a Xeroform gauze dressing. All wounds were non infected, Wagner stage II or III and received standard care including debridement, non weight bearing limb support and weekly wound evaluation. The mean time to heal in the MC (±SE) treated group was 32 days ± 2·5 and for controls it was 48 days ± 4·7 (P < 0·01). The rate of weekly wound closure (mean ± SE) was 1·7 times faster in the MC‐treated group (cellulose treated, ?5·04% per week ± 0·38 versus control, ?2·93% per week ± 0·19), (P < 0·001). Among covariants tested by univariate regression, only the original wound area correlated with the time to wound closure (P < 0·001). In conclusion, with the provision of current standards of care, the application of an MC dressing to a diabetic ulcer may enhance the rate of wound healing and shorten the time course of epithelisation.     

Use of epidermal skin grafts in chronic wounds: a case series

In stalled, chronic wounds, more aggressive and proactive wound closure efforts are needed. We describe adjunctive use of epidermal grafting in patients with chronic wounds. Wound bed preparation consisted of surgical necrotectomy or sharp debridement, hyperbaric oxygen therapy, negative pressure wound therapy, compression therapy, platelet‐rich plasma therapy and/or heparan sulphate agents. Epidermal grafts were harvested from the patient's thigh and applied to the wound. Wound and donor site healing was monitored. A total of 78 patients (average age = 64·1 ± 15·6 years) were included in the study. Common comorbidities included hypertension (47·4%), venous insufficiency (37·2%) and obesity (28·2%). Average wound duration was 13·2 months (range: 0·3–180 months). The most common wound types were dehiscence (29·5%), radiation ulcer (24·4%) and venous ulcer (17·9%). Total time from epidermal grafting to wound closure was 10·0 ± 7·3 weeks. Of the 78 wounds, 66 (84·6%) reached full wound closure (49 < 3 months, 16 > 3 months, 1 without time data). Of 78 wounds, 10 (12·8%) underwent partial wound healing, while 2 wounds (2/78; 2·6%) remained unhealed. These results suggest that wound surface reduction can be achieved by proactive early application of biological therapies and epidermal skin grafts, which may help decrease time to wound healing.     

Systematic review and meta‐analysis of the efficacy of epidermal grafting for wound healing

Autologous skin grafting is an important method for wound coverage; however, it is an invasive procedure and can cause donor site morbidity. Epidermal grafting (EG) enables epidermal transfer to wounds with minimal donor site morbidity. However, data to date have been heterogeneous. This study aims to synthesise the current evidence on EG for wound healing to establish the efficacy of this surgical technique. A comprehensive search in the MEDLINE, EMBASE and CENTRAL databases was conducted. The endpoints assessed were proportion of wounds healed and mean wound‐healing time. This systematic review was conducted and reported according to the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We identified 1568 articles, of which seven articles were included in this review – a total of 209 wounds in 190 patients. The mean wound duration was 17·06 weeks (95% CI 8·57–25·55). Of these, 71·5% (95% CI 56·7–84·2) of the wounds achieved complete healing. Mean time for complete wound healing was 5·53 weeks (95% CI 3·18–7·88). The mean donor site healing time was 7·48 days (95% CI 4·83–10·13), with no reported donor site morbidity. The current data are small and lack level 1 evidence.     

Negative pressure wound therapy as an adjunct in healing of chronic wounds

Negative pressure wound therapy (NPWT) has emerged as a cutting‐edge technology and provides an alternative solution to the problem of wounds. This study was undertaken to assess the efficacy of this technique in the treatment of chronic wounds. A prospective clinical study was used to evaluate our experience in use of NPWT in the healing of pressure ulcers and chronic wounds over 2 years. The primary end point of the study group was the time taken for appearance of healthy granulation tissue and full reepithelialisation without drainage. All patients with sepsis were excluded from the study. The statistical analysis of the data was carried out. Of the 60 patients studied, 41 had associated comorbidities including diabetes mellitus. The commonest site of occurrence was the lower limb. Coverage in the form of a flap was required at presentation in 63·33% of patients. However, after initiation of NPWT, none of them required the procedure and they healed spontaneously either by secondary intention or by skin grafting. The time taken for appearance of healthy granulation tissue was 14·36 ± 4·24 days. Complete healing of wounds occurred by 33·1 ± 10·22 days. There was a statistically significant difference in the volume of the wounds before and after the intervention (P = 0·000). Complications resulting from NPWT were minimal. This technique is an excellent adjunct to surgical debridement.     

Suboptimal identification of patient‐specific risk factors for poor wound healing can be improved by simple interventions

Poor wound healing is an important surgical complication. At‐risk wounds must be identified early and monitored appropriately. Wound surveillance is frequently inadequate, leading to increased rates of surgical site infections (SSIs). Although the literature demonstrates that risk factor identification reduces SSI rates, no studies have focused on wound management at a junior level. Our study assesses documentation rates of patient‐specific risk factors for poor wound healing at a large district general hospital in the UK. It critically evaluates the efficacy of interventions designed to promote surveillance of high‐risk wounds. We conducted a full‐cycle clinical audit examining medical records of patients undergoing elective surgery over 5 days. Interventions included education of the multidisciplinary team and addition of a Wound Healing Risk Assessment (WHRA) checklist to surgical admissions booklets. This checklist provided a simple stratification tool for at‐risk wounds and recommendations for escalation. Prior to interventions, the documentation of patient‐specific risk factors ranged from 0·0% to 91·7% (mean 42·6%). Following interventions, this increased to 86·4–95·5% (mean 92·5%), a statistically significant increase of 117·1% (P < 0·01). This study demonstrates that documentation of patient‐specific risk factors for poor wound healing is inadequate. We have shown the benefit of introducing interventions to increase risk factor awareness.     

Analysis of pressure ulcer wound fluid using two‐dimensional electrophoresis

The incidence rate of pressure ulcers in the USA ranges from 0·4% to 38% in acute care settings and from 2·2% to 23·9% in long‐term care settings, and their treatment costs are in the billions of dollars yearly. The proteome of wound fluid may contain early indicators or biomarkers associated with healing in pressure ulcers that would enable treatment regimes to be optimised for each individual. Wound fluid was collected from the interior and periphery of 19 chronic pressure ulcers at 15 time points during 42 days for an analysis of protein expression. Proteins were fractionated using two‐dimensional polyacrylamide gel electrophoresis. A comparison of the spot distributions indicates a biochemical difference between the interior and the periphery of wounds. Pressure ulcers that healed show a greater number of spots for interior and peripheral locations combined over time when compared with wounds that did not heal. Using this technique, protein S100A9 was identified as a potential biomarker of wound healing. The identification of differences within the proteome of healing versus non healing pressure ulcers could have great significance in the use of current treatments, as well as the development of new therapeutic interventions.     

A PEGylated fibrin hydrogel‐based antimicrobial wound dressing controls infection without impeding wound healing

Combat injuries are associated with a high incidence of infection, and there is a continuing need for improved approaches to control infection and promote wound healing. Due to the possible local and systemic adverse effects of standard 1% cream formulation (Silvadene), we had previously developed a polyethylene glycol (PEGylated) fibrin hydrogel (FPEG)‐based wound dressing for the controlled delivery of silver sulfadiazine (SSD) entrapped in chitosan microspheres (CSM). In this study, we have evaluated the antimicrobial and wound healing efficacy of SSD‐CSM‐FPEG using a full‐thickness porcine wound infected with Pseudomonas aeruginosa. Infected wounds treated with a one‐time application of the SSD‐CSM‐FPEG wound dressing demonstrated significantly reduced bacterial bioburden over time (99·99% of reduction by day 11; P < 0·05) compared with all the other treatment groups. The epithelial thickness and granulation of the wound bed was significantly better on day 7 (150·9 ± 13·12 µm), when compared with other treatment groups. Overall, our findings demonstrate that the SSD‐CSM‐FPEG wound dressing effectively controls P. aeruginosa infection and promotes wound healing by providing a favourable environment that induces neovascularisation. Collectively, sustained release of SSD using fibrin hydrogel exhibited enhanced benefits when compared with the currently available SSD treatment, and this may have significant implications in the bacterial reduction of infected wounds in military and civilian populations.     

Transplantation of BMSCs expressing hVEGF165/hBD3 promotes wound healing in rats with combined radiation‐wound injury

The combined radiation‐wound injury is a refractory wound with decreased number or dysfunction of repairing cells and growth factors. This remains a challenge in clinical practice. The object of this study is to evaluate the therapeutic efficacy of a combination of human vascular endothelial growth factor 165 (hVEGF₁₆₅) and human beta‐defensin 3 (hBD3) in the treatment of such wounds. A plasmid‐carrying hVEGF₁₆₅ gene and hBD3 gene was used to transfect rat bone‐marrow‐derived mesenchymal stem cells (BMSCs). The supernatant from the modified BMSCs significantly promoted the proliferation and cell migration of human endothelial cells and it also inhibited the growth of bacteria and fungus, demonstrating the successful expression of the transfected genes. The hVEGF₁₆₅/hBD3‐modified BMSCs were then injected into the sites of combined radiation‐wound injury on rats. It demonstrated that wound‐healing time was shortened significantly in the treated rats. The granulation tissue formation/maturation, skin appendage regeneration and collagen deposition were also improved significantly. Strong expression of hVEGF₁₆₅ and hBD3 was detected in the wound surface at early stage of the healing. The results indicate that topical transplantation of hVEGF₁₆₅/hBD3‐modified BMSCs promoted wound healing, and this gene therapy strategy presents a promising approach in the treatment of refractory wounds such as the combined radiation‐wound injury.