Topical embryonic stem cells enhance wound healing in diabetic rats

The effects of embryonic stem cells (ESCs) on diabetic wound healing were investigated using an excisional skin wound model in 110 diabetes‐induced rats. We transplanted a clonal population of ESCs (5 × 10⁶) by topical injection into full thickness skin wounds. Four study groups were used; nondiabetic rats as a control, non‐insulin controlled diabetic rats not treated with ESCs, insulin controlled diabetic rats not treated with ESCs, and insulin controlled diabetic rats treated with ESCs. Five rats in each experimental group were sacrificed on days 1, 5, 10, 15, and 20 after wounding. Wounds images were acquired daily and wound sizes were calculated. We measured the mRNA levels of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), and fibronectin levels in extracellular matrix, and assessed wound healing by assessing histological parameters of epidermal regeneration, granulation tissue thickness, and angiogenesis. In the ESC‐treated group, wound sizes were significantly smaller than in the insulin controlled diabetic group not treated with ESCs on days 5 and 10 (p < 0.05), and EGF and VEGF levels were markedly higher on days 5 and 10, fibronectin levels on day 5 after injection. All histological scores in the ESC‐treated group were significantly higher than those of the insulin controlled diabetic group on day 5 (p < 0.05). Our results shows that topical ESCs enhance diabetic wound healing during the early stage, and suggest that ESCs transplantation offers a novel therapeutic modality for the treatment of diabetic wounds. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1554–1562, 2011     

The efficacy and safety of epidermal growth factor in treatment of diabetic foot ulcers: the preliminary results

Objective: To evaluate the efficacy and safety of recombinant human epidermal growth factor (rh‐EGF) in healing foot ulcers in diabetic patients. Methods: A total of 28 subjects with foot ulcers were recruited into the pilot study. Patients who had obvious peripheral arterial disease, trans‐tibial amputation, plastic surgery or skin flap, and skin graft were excluded. The properly debrided wounds and the non closure wounds after toe amputation were included. When the wounds became clean or uninfected, they received twice‐a‐day treatment with 0·005% Easyef and hydrocolloid dressing. The size and severity of the wounds were evaluated. Others such as blood sugar, renal and hepatic function, serum albumin, vascular condition, foot infection or osteomyelitis were assessed. Results: All of 28 patients had positive response of granulation (100%). Complete healing was noted in 13 out of 23 subjects and finished 8‐week follow‐up (56·5%). The rates of wound closure were 43·3%, 59·9%, 68·7%, and 84·8% in week 2, 4, 6 and 8, respectively, regardless of the severity. Being dropped out, three patients needed further interventions. No skin allergic reaction. Over‐granulation was observed in one female patient (3·7%), but as minor. Conclusions: Easyef has positive effects on healing of moderate‐to‐severe foot ulcers and demonstrated being safe to diabetic patients. The drug had high tolerability and compliance.     

Evaluation of the use of recombinant human basic fibroblast growth factor in combination with negative pressure wound therapy with instillation and dwell time in porcine full‐thickness wound model

NPWT with instillation and dwell time (NPWTi‐d), which combines NPWT with wound irrigation, has been clinically applied as a more effective treatment than conventional NPWT. Commercially available recombinant human basic fibroblast growth factor (rh‐bFGF) has been demonstrated to be beneficial for use over the wound beds. The objective of this study was to evaluate the effectiveness of combined treatment with NPWTi‐d and rh‐bFGF. Six pigs received 12 full‐thickness excisional skin wounds and were treated with six different treatment groups for each pair. The treatment regimens were composed NPWTi‐d, NPWT, or advanced wound care with or without rh‐bFGF. On day 6, the minimum granulation tissue thickness and blood vessel number of the group of combined treatment with NPWTi‐d and rh‐bFGF spray were significantly greater than that of the control group. Combined treatment with NPWTi‐d and rh‐bFGF spray reads to good granulation tissue formation and vascularization for accelerating wound healing.     

A pilot study evaluating non‐contact low‐frequency ultrasound and underlying molecular mechanism on diabetic foot ulcers

Non‐contact low‐frequency ultrasound (NCLF‐US) devices have been increasingly used for the treatment of chronic non‐healing wounds. The appropriate dose for NCLF‐US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non‐healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non‐healing DFUs for 5 weeks receiving standard of care and/or NCLF‐US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF‐US thrice per week (Group 1), NCLF‐US once per week (Group 2) and the control (Group 3) that received no NCLF‐US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of pro‐inflammatory cytokines (IL‐6, IL‐8, IL‐1β, TNF‐α and GM‐CSF), matrix metalloproteinase‐9 (MMP‐9), vascular endothelial growth factor (VEGF) and macrophages in response to NCLF‐US consistent with wound reduction, when compared with control group subjects. This proof‐of‐concept pilot study demonstrates that NCLF‐US is effective in treating neuropathic diabetic foot ulcers through, at least in part, inhibiting pro‐inflammatory cytokines in chronic wound and improving tissue regeneration. Therapeutic application of NFLU, thrice (3) per week, renders the best wound area reduction.     

Epidermal growth factor‐containing wound closure enhances wound healing in non‐diabetic and diabetic rats

Background: This study was designed to elucidate the in vivo efficacy of epidermal growth factor (EGF) on wound healing in non diabetic and diabetic rats. Methods: Ninety‐six male Wistar‐Albino rats were randomly divided into six groups. Saline‐moistened gauze, pure gelatin or EGF in gelatin‐microsphere dressings were used in a dermal excision model in both normal and streptomycin‐induced diabetic rats. Wound healing was evaluated on day 7 and 14. Reduction in wound area, hydroxypyroline content and tensile strength of the wound were evaluated in each rat. Tissue samples taken from the wounds were examined histopathologically for reepithelialisation, cellular infiltration, number of fibroblasts, granulation and neovascularisation. Results: On day 7, the use of EGF‐containing dressing was observed to reduce the wound area better when compared with the other dressings tested. This effect was significant in normal rats rather than diabetic rats. The difference in reduction of wound area did not persist on day 14. No significant effect on hydroxyproline content of the wound was found with EGF‐containing dressing in either normal or diabetic rats. There was a statistically significant increase in tensile strength values of EGF‐applied non diabetic rats over the 14 day period. An increase in tensile strength was prominent in also EGF‐applied diabetic rats on day 14. Histological examination revealed higher histopathologic scores in EGF‐applied diabetic and non diabetic rats. Conclusion: These findings implicate that use of EGF in gelatin‐microsphere dressings improves wound healing both in normal and diabetic rats.     

Coacervate delivery of HB‐EGF accelerates healing of type 2 diabetic wounds

Chronic wounds such as diabetic ulcers pose a significant challenge as a number of underlying deficiencies prevent natural healing. In pursuit of a regenerative wound therapy, we developed a heparin‐based coacervate delivery system that provides controlled release of heparin‐binding epidermal growth factor (EGF)‐like growth factor (HB‐EGF) within the wound bed. In this study, we used a polygenic type 2 diabetic mouse model to evaluate the capacity of HB‐EGF coacervate to overcome the deficiencies of diabetic wound healing. In full‐thickness excisional wounds on NONcNZO10 diabetic mice, HB‐EGF coacervate enhanced the proliferation and migration of epidermal keratinocytes, leading to accelerated epithelialization. Furthermore, increased collagen deposition within the wound bed led to faster wound contraction and greater wound vascularization. Additionally, in vitro assays demonstrated that HB‐EGF released from the coacervate successfully increased migration of diabetic human keratinocytes. The multifunctional role of HB‐EGF in the healing process and its enhanced efficacy when delivered by the coacervate make it a promising therapy for diabetic wounds.     

The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo

Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high‐voltage and high‐frequency power supply. Eight‐week‐old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low‐dose group), and 180s' CAP (high‐dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound‐healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low‐dose group and high‐dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL‐6, tumour necrosis factor‐α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor‐β in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound‐healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.     

Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice

Impaired wound healing leading to skin ulceration is a serious complication of diabetes and may be caused by defective angiogenesis. Endothelial progenitor cells (EPCs) can augment neovascularisation in the ischaemic tissue. Experiments were performed to test the hypothesis that locally administered EPCs can promote wound healing in diabetes. Full‐thickness skin wounds were created on the dorsum of diabetic mice. EPCs were obtained from bone marrow mononuclear cells (BMMNCs) and applied topically to the wound immediately after surgery. Vehicle and non‐selective BMMNCs were used as controls. Wound size was measured on days 5, 10 and 14 after treatment, followed by resection, histological analysis and quantification of vascularity. Topical application of EPCs significantly promoted wound healing, as assessed by closure rate and wound vascularity. Immunostaining revealed that transplanted EPCs induced increased expression of vascular endothelial growth factor and basic fibroblast growth factor. Few EPCs were observed in the neovasculature based on in vivo staining of the functional vasculature. Ex vivo expanded EPCs promote wound healing in diabetic mice via mechanisms involving increased local cytokine expression and enhanced neovascularisation of the wound. This strategy exploiting the therapeutic capacity of autologously derived EPCs may be a novel approach to skin repair in diabetes.     

Growth factor therapy in patients with partial‐thickness burns: a systematic review and meta‐analysis

Growth factor (GF) therapy has shown promise in treating a variety of refractory wounds. However, evidence supporting its routine use in burn injury remains uncertain. We performed this systematic review and meta‐analysis assessing randomised controlled trials (RCTs) to investigate efficacy and safety of GFs in the management of partial‐thickness burns. Electronic searches were conducted in PubMed and the Cochrane databases. Endpoint results analysed included wound healing and scar formation. Thirteen studies comprising a total of 1924 participants with 2130 wounds (1131 GF receiving patients versus 999 controls) were identified and included, evaluating the effect of fibroblast growth factor (FGF), epidermal growth factor (EGF) and granulocyte macrophage‐colony stimulating factor (GM‐CSF) on partial‐thickness burns. Topical application of these agents significantly reduced healing time by 5·02 (95% confidence interval, 2·62 to 7·42), 3·12 (95% CI, 1·11 to 5·13) and 5·1 (95% CI, 4·02 to 6·18) days, respectively, compared with standard wound care alone. In addition, scar improvement following therapy with FGF and EGF was evident in terms of pigmentation, pliability, height and vascularity. No significant increase in adverse events was observed in patients receiving GFs. These results suggested that GF therapy could be an effective and safe add‐on to standard wound care for partial‐thickness burns. High‐quality, adequately powered trials are needed to further confirm the conclusion.     

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.     

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.     

Comparison of human umbilical cord blood‐derived mesenchymal stem cells with healthy fibroblasts on wound‐healing activity of diabetic fibroblasts

Various types of skin substitutes composed of fibroblasts and/or keratinocytes have been used for the treatment of diabetic ulcers. However, the effects have generally not been very dramatic. Recently, human umbilical cord blood‐derived mesenchymal stromal cells (hUCB‐MSCs) have been commercialised for cartilage repair as a first cell therapy product using allogeneic stem cells. In a previous pilot study, we reported that hUCB‐MSCs have a superior wound‐healing capability compared with fibroblasts. The present study was designed to compare the treatment effect of hUCB‐MSCs with that of fibroblasts on the diabetic wound healing in vitro. Diabetic fibroblasts were cocultured with healthy fibroblasts or hUCB‐MSCs. Five groups were evaluated: group I, diabetic fibroblasts without coculture; groups II and III, diabetic fibroblasts cocultured with healthy fibroblasts or hUCB‐MSCs; and groups IV and V, no cell cocultured with healthy fibroblasts or hUCB‐MSCs. After a 3‐day incubation, cell proliferation, collagen synthesis levels and glycosaminoglycan levels, which are the major contributing factors in wound healing, were measured. As a result, a hUCB‐MSC‐treated group showed higher cell proliferation, collagen synthesis and glycosaminoglycan level than a fibroblast‐treated group. In particular, there were significant statistical differences in collagen synthesis and glycosaminoglycan levels (P = 0·029 and P = 0·019, respectively). In conclusion, these results demonstrate that hUCB‐MSCs may have a superior effect to fibroblasts in stimulating diabetic wound healing.     

Negative‐pressure wound dressings to secure split‐thickness skin grafts in the perineum

Several researches have shown that negative‐pressure wound dressings can secure split‐thickness skin grafts and improve graft survival. However, in anatomically difficult body regions such as the perineum it is questionable whether these dressings have similar beneficial effects. In this study, we evaluated the effects of negative‐pressure wound dressings on split‐thickness skin grafts in the perineum by comparing wound healing rate and complication rate with that of tie‐over dressings. A retrospective chart review was performed for the patients who underwent a split‐thickness skin graft to reconstruct perineal skin defects between January 2007 and December 2011. After grafting, the surgeon selected patients to receive either a negative‐pressure dressing or a tie‐over dressing. In both groups, the initial dressing was left unchanged for 5 days, then changed to conventional wet gauze dressing. Graft success was assessed 2 weeks after surgery by a single clinician. A total of 26 patients were included in this study. The mean age was 56·6 years and the mean wound size was 273·1 cm². Among them 14 received negative‐pressure dressings and 12 received tie‐over dressings. Negative‐pressure dressing group had higher graft taken rate (P = 0·036) and took shorter time to complete healing (P = 0·01) than tie‐over dressing group. The patients with negative‐pressure dressings had a higher rate of graft success and shorter time to complete healing, which has statistical significance. Negative‐pressure wound dressing can be a good option for effective management of skin grafts in the perineum.     

The possibility of microbial cellulose for dressing and scaffold materials

In recent years, natural polymers such as cellulose, alginate and chitosan have been used worldwide as biomedical materials and devices, as they offer more advantages over synthetic polymers. The aim of this study was to clarify the usefulness of microbial cellulose (MC) for use as a dressing and scaffold material. For evaluating the biodegradability and toxicity of MC, we divided the rats (n = 12) into two groups (the implanted group and the non‐implanted group). In the implanted group, we implanted the film type of MC in the backs of six rats. In the non‐implanted group, however, we did not implant the film type of MC in the backs of the six rats. Four weeks later, we compared two groups by the gross, histological and biochemical characteristics by using blood and tissue samples. To evaluate the wound healing effects of MC, three full‐thickness skin defects were made on the backs of each rat (n = 20). Three wounds on the backs of the same rats were treated with other dressing materials, namely, Vaseline gauze (group Con), Algisite M^® (group Alg) and MC (group MC). We analysed the gross, histological and biochemical characteristics by western blotting. MC was found to be biodegradable and non‐toxic. On day 3, the MC film was visible under the subcutaneous tissue; however, after 4 weeks, no remnants of the film were visible under the subcutaneous tissue. Furthermore, there was no evidence of MC‐induced toxicity. Moreover, group MC showed more rapid wound healing compared with group Con. On day 14 after skin excision, group MC showed greater decrease in wound size compared with group Con (33% versus 7·2%). The wound healing effects were also substantiated by the histological findings (greater reduction in inflammation and rapid collagen deposition as well as neovascularisation) and western blotting (decreased expression of vascular endothelial growth factor and transforming growth factor‐β1 in group MC on day 14 after skin excision, unlike group Con). This study showed that, in addition to having wound healing effects, MC is biodegradable and non‐toxic and can, therefore, be used as a dressing and scaffold material.     

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.     

多种生长因子促糖尿病患者难愈合性创面愈合的临床研究

目的　观察多种生长因子治疗糖尿病难愈合性创面的临床效果,并探讨其可能的机制。方法　将７８ 例糖尿病患者分为三组,即生理盐水对照组、表皮细胞生长因子（ Ｅ Ｇ Ｆ）治疗组、血小板源伤口愈合因子（ Ｐ Ｄ Ｗ Ｈ Ｆ）治疗组。观察治疗后１～８ 周创面闭合指数、创面治愈率及组织形态学变化。结果　 Ｅ Ｇ Ｆ组、 Ｐ Ｄ Ｗ Ｈ Ｆ组的创面闭合指数、创面治愈率较对照组明显增加,其肉芽组织毛细血管与成纤维细胞增生、胶原沉积和表皮覆盖明显,尤以溃疡与正常组织交界处明显。组间比较发现, Ｐ Ｄ Ｗ Ｈ Ｆ的促愈合作用优于 Ｅ Ｇ Ｆ。结论　局部应用多种生长因子可治疗糖尿病难愈合性创面,生长因子单独或配伍使用是改善糖尿病患者创面愈合受阻的有效措施。     

EGF increases short-term type I collagen accumulation during wound healing in diabetic rats

Continuous topical application of epidermal growth factor (EGF) to granulation tissue increases the rate of collagen accumulation. It is believed that the clinical use of growth factors, such as EGF, may become common in the treatment of impaired wound healing in the near future. Impairments in the production and degradation of wound collagens have been demonstrated in diabetes mellitus. We studied the effects of a single, local application of EGF on collagen content, collagenase activity, and the ratio of type III and type I collagens within granulation tissue using polytetrafluoroethylene (PTFE) wound cylinders in 48 streptozotocin-induced diabetic rats in order to determine potential benefits of EGF to wound healing in diabetics. Wound collagen content in EGF-treated diabetic animals was significantly higher than in diabetic controls during the first 10 days of wound healing (236% on day 5, P less than .001; 140% on day 10, P less than .01), but decreased to significantly lower levels by day 15 of healing (71% of diabetic controls, P less than .01; 47% of nondiabetic controls, P less than .01). An 18% increase in diabetic wound protease activity was observed following application of EGF (P less than .001). The ratio of type III collagen to total wound collagen within the granulation tissue was significantly reduced (P less than .001) following EGF application. We demonstrate that a single, topical application of EGF promotes early synthesis of type I collagen, thereby deranging the usual type III/total collagen ratio, and is associated with increased wound protease activity.     

Improvement of wound tissue repair by chitosan films containing (–)‐borneol,a bicyclic monoterpene alcohol,in rats

The aim of this study was to investigate the wound‐healing activity of (–)‐borneol (BOR) incorporated in chitosan film on healing protocol in rodents. To assess the BOR wound‐healing potential, male Wistar rats were subjected to a full‐thickness excisional wound. The animals were divided into three groups: dressed with chitosan‐based film (QUIN); dressed with chitosan‐based film containing 0·5% BOR (QUIBO05); or dressed with chitosan‐based film containing 1% BOR (QUIBO1). Dressing the wound areas and histological analysis were performed on the 3rd, 7th, 14th, and 21st days. The myeloperoxidase (MPO) activity was assessed on the third and seventh days after surgical procedures. Wounds dressed with chitosan‐based film containing BOR reduced significantly the MPO activity (P < 0·001), showed significantly larger wound retraction rates (7 days, P < 0·05), improved the granulation reaction, and also provided better collagenisation density and arrangement during wound healing. It is suggested that BOR modulates the wound‐healing process and is a promising compound to be used in wound care. This product may be quite useful in improving wound healing and could be a new biotechnological product with healing properties and clinical application. Further ongoing studies will enable us to understand the precise mechanisms whereby BOR improves the wound‐healing process.     

Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective,randomised, multicentre study

This 12‐week, prospective, randomised, controlled multi‐centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix (AM) (study group) and standard of care (control group) therapies. Eighty‐six patients were randomised into study (47 patients) and control (39 patients) groups. No significant differences in demographics or pre‐treatment ulcer data were calculated. Complete healing and mean healing time were 69·6% and 5·7 weeks, respectively, for the study group and 46·2% and 6·8 weeks, respectively, for the control group. The proportion of healed ulcers between the groups was statistically significant (P = 0·0289), with odds of healing in the study group 2·7 times higher than in the control group. Kaplan–Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate (P = 0·015) for the control group (53·9%) compared with the study group (30·4%). After adjusting for ulcer size at presentation, which was a statistically significant covariate (P = 0·0194), a statistically significant difference in non healing rate between groups was calculated (P = 0·0233), with odds of healing 2·0 times higher in the study versus control group. This study supports the use of single‐application AM therapy as an effective treatment of diabetic, neuropathic ulcers.     

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.