Suprathel-an innovative, resorbable skin substitute for the treatment of burn victims

Autologous split skin grafts are the most reliable method for closing third degree burns. Under this scheme, donor sites as well as second degree burns under conservative treatment, however, would benefit from rapid wound closure. For this treatment, biological as well as synthetic materials are available. For the improvement of these materials, primary goals are pain reduction and easy handling in the absence of biological risk. From a synthetic copolymer mainly based on DL-lactic acid a new skin substitute was developed, marketed as Suprathel. Within the scope of a bicentric study Suprathel was compared versus paraffin gauze intraindividually applied on split skin donor sites. Wound pain was measured on the Visual Pain Analog Scale over a period of 10 days as the critical criterion. Accordingly Suprathel versus Omiderm were compared on second degree burns (degree 2a, partial thickness burns). In both study parts, Suprathel significantly reduced pain. Its easy handling was superior compared to other materials. The Suprathel membrane adhered rapidly to the wound thus protecting against infections and promoting wound healing. No allergic reactions were observed. The ability of the material to resorb ensured pain-free removal after complete healing of the wound.     

Full-thickness skin columns: A method to reduce healing time and donor site morbidity in deep partial-thickness burns

The current standard of care for the coverage of large wounds often involves split thickness skin grafts (STSGs) which have numerous limitations. One promising technique that has gained traction is fractional autologous skin grafting using full-thickness skin columns (FTSC). Harvesting occurs orthogonally by taking numerous individual skin columns containing the epidermis down through the dermis and transferring them to the wound bed. The purpose of this porcine study was to investigate the efficacy of implanting FTSCs directly into deep partial-thickness burn wounds, as well as examining donor site healing at the maximal harvest density. It was hypothesised that by utilising FTSCs, the rate of healing in deep partial thickness burns can be improved without incurring the donor morbidity seen in other methods of skin grafting. Deep partial-thickness burns were created on the dorsum of female red duroc swine, debrided 3 days later and FTSCs were implanted at varying expansion ratios directly into the burn wounds. At day 14, 1:50 expansion ratio showed significantly faster re-epithelialisation compared to the debrided burn control and 1:200. Donor sites (at 7%–10% harvest density) were 100% re-epithelialised by day 7. Additionally, the maximal harvest density was determined to be 28% in an ex vivo model, which then five donor sites were harvested at 28% density on a red duroc swine and compared to five STSG donor sites. At maximal harvest density, FTSC donor sites were significantly less hypopigmented compared to STSGs, but no significant differences were observed in re-epithelialisation, contraction, blood flow or dermal thickness. In conclusion, implantation directly into deep partial-thickness burns is a viable option for the application of FTSCs, favouring lower expansion ratios like 1:50 or lower. Little difference in donor site morbidity was observed between FTSC at a maximal harvest density of 28% and STSGs, exceeding the optimal harvest density.     

Efficacy of treatment with Repithel and Jelonet in comparison to treatment with Jelonet alone - a randomized clinical trial in patients receiving meshed skin grafts

Moist wound treatment is a well recognized method for the treatment of aseptic acute and chronic wounds. While the moist environment is beneficial to the woundhealing process, it also increases the risk of bacterial superinfection. We here report on the results of a clinical phase-III-study in which we tested the effect of a new PVP-iodine liposomal hydrogel (Repithel) on split-thickness skin grafts. This formulation optimizes moist wound treatment by improving the cell proliferation rate while preventing wound infection. AIM: The aim of this phase-III-study was to analyse the efficacy and tolerance of Repithel in patients receiving meshed skin grafts. METHODS: 167 patients with transplantation wounds were either treated with lipid gauze alone (control group) or with lipid gauze and Repithel. In both groups the extent of neoepithelization, the frequency and severity of graft losses and the time until complete wound closure was achieved were determined. Analysis of the re-epithelization was achieved by photoplanimetry. Impedance measurements gave additional information on the regeneration of the epidermal barrier. RESULTS: Wounds receiving Repithel showed a significantly faster neoepithelisation than wounds which were treated with lipid gauze alone. Treatment with Repithel significantly reduced both the number of graft losses and the size of area lost. The time until wounds were closed completely was significantly shorter in patients receiving Repithel than in controls. The positive effects of Repithel on wound healing were especially observed in smokers, patients with chronic wounds, burns or infected wounds. CONCLUSIONS: Repithel supports healing of meshgraft transplants and reduces the risk of graft loss. Patients who heal poorly benefit particularly from the Repithel treatment.     

A recombinant human collagen hydrogel for the treatment of partial-thickness burns: A prospective,self-controlled clinical study

IntroductionAllogeneic and xenogeneic skin are recognized as the best coverings for skin burn wounds, but currently face a supply shortage. To solve this problem, our research group developed a standardized manufactured hydrogel dressing based on a new type of highly bioactive recombinant human collagen.Study designProspective self-controlled trial.ObjectiveTo evaluate the efficacy and safety of recombinant human collagen hydrogel in the treatment of partial burn wounds to the skin compared to those of xenogeneic skin.MethodsThis study included twenty-one patients admitted to Shanghai Changhai Hospital within 48 h after receiving partial-thickness skin burns. The wounds were symmetrically separated along the axis and treated with recombinant human collagen hydrogel (RHCH) or a human-CTLA4-Ig gene-transferred pig skin xenotransplant. The condition of the wound surfaces was recorded on days 0 (of enrollment), 5, 10, 15, and 20, and bacterial drug sensitivity testing, hematuria examination, and electrocardiographic tests were conducted on days 0, 10, 20, or on the day of wound healing.ResultsThere were no statistically significant differences in wound healing time between the two groups. The median number of days to healing was 11.00 ± 0.56 for xenogeneic skin vs. 11.00 ± 1.72 for RHCH.ConclusionDuring the observation period, the therapeutic effect of the RHCH developed by our group on partial-thickness burn wounds was not significantly different from that of gene-transferred xenogeneic skin. Thus, our designed RHCH shows potential for clinical use to treat burn wounds on the skin.     

Integra as a dermal replacement in a meshed composite skin graft in a rat model: a one-step operative procedure.

BACKGROUND: Current use of Integra, the collagen-based dermal analogue, requires a two-step grafting procedure to achieve wound closure with an "ultrathin" autograft. METHODS: A one-step operative procedure of meshed composite skin graft (MCSG) using Integra as a dermal template for a meshed split thickness autograft was developed in rats. The silicon layer of Integra was removed, the resulting dermal analogue was meshed (1:1.5), expanded, and placed on excised full thickness wound and covered with a meshed (1:1.5 or 1:6) split thickness autograft. Grafted wounds were dressed with BioBrane, Vaseline gauze, silver-impregnated nylon, or silver-nylon and direct current (SNDC). At scheduled intervals up to 3 months postgrafting, wounds were examined for epithelialization, collagen deposition and fibrosis, hair growth, and contraction. The results of wound closure and healing following the one-step procedure were compared with the outcome of the two-step grafting procedure where application of meshed Integra (step one) was followed in 14 days by removal of the silicon layer and application of the meshed autograft (step two). RESULTS: The one-step procedure applied to meshed autograft/Integra (1:1.5/1:1.5) composite graft accelerated wound closure by 6-19 days when compared with the two-step procedure. At 3 months postgrafting, the contraction of the healed wound dressed with SNDC, BioBrane, or Vaseline gauze was reduced by 13-16% following the one-step procedure compared with the two-step procedure (p < 0.05). The one-step procedure allowed the expansion of the autograft layer to 1:6 while achieving wound healing results similar to grafting with 1:1.5 meshed autograft layer using the two-step grafting procedure. CONCLUSION: Single-step application of meshed, thin, split thickness autograft over meshed Integra-derived dermal substitute allows more rapid wound closure with less contraction and more efficient use of graft donor skin than can be obtained with the commonly used two-step grafting procedure.     

The use of split-thickness dermal grafts to resurface full thickness skin defects

Coverage of large burns may be difficult when skin graft donor sites are limited. This study explored the use of the split-thickness dermal graft (STDG), as an alternative to the standard split-thickness skin graft (STSG). STSGs and STDGs were compared experimentally by their ability to resurface full thickness skin defects in a pig model. Both types of grafts were harvested from the backs of six pigs and placed on full thickness wounds. From the same donor site a 0.012 in. thick STSG and another two 0.012 in. thick STDGs were harvested. Thus the deep surface of grafts measured 0.012, 0.024 and 0.036 in. from the skin surface, respectively. All grafts were placed on 6 cm×6 cm full thickness wounds. The donor areas healed at 1 week. Epithelialization of the STDGs, was assessed by computerized planimetry, and was 100% at 4 weeks. Graft biopsies revealed that STSGs were significant thinner than STDGs at 1 week (P=0.0422, 0.0135), 2 weeks (P=0.0240) and 4 weeks (P=0.0516, 0.0425). We conclude that STDGs my provide definitive coverage of full thickness skin deficits in a pig wound model.     

Novel cryoprecipitate for wound healing and skin grafts in rats

The authors sought to evaluate the ability of locally administered enhanced cryoprecipitate (eCryo) to improve the wound healing of split thickness skin grafts (STSG) and their donor sites. An STSG (5 × 5 cm) was harvested on the back of 30 rats and divided into four areas that were then treated in one of the following groups: A: ‘standard’ dressing without STSG; B: eCryo without STSG; C: eCryo with STSG coverage and D: STSG alone. Macroscopic and histological assessments (histomorphometric grading scale and cellular composition) were evaluated at days 7, 14, 21 and 28 for wound healing. All wound beds as well as STSGs healed well without any complications. Eighty per cent of the STSG showed a histological graft take of >75% after 28 days. There were no statistically significant differences of macroscopic or histological results between the groups at any time point. Preparation of eCryo is easy and effective. Its use as an adhesive for STSGs is safe and shows similar results as controls. The theoretical benefits of eCryo did not show significant differences. Possible reasons as well as important findings for future research on wound healing are discussed.     

体外构建复合皮移植后对大鼠创面愈合的影响

目的：观察角质形成细胞和成纤维细胞与无细胞异种真皮基质构成的复合皮移植于全层皮肤缺损创面后的效果,寻找一种新的创面覆盖物。方法：54只SD大鼠作背部全层皮肤缺损创面后分为A、B、C三组,分别以A型复合皮（角质形成细胞＋成纤维细胞＋无细胞异种真皮基质）、B型复合皮（角质形成细胞＋无细胞异种真皮基质）和普通敷料进行移植,术后定期观察创面愈合情况并进行创面收缩率的计算,同时切取创面组织进行组织学检测。结果：三组中,A组的创面愈合及外观情况最好;A组创面收缩率明显低于B、C两组（P（0．05）;组织学检测提示A组复合皮上皮分化充分,胶原增生有序,表皮一真皮连接结构重建明显,未见明显的急性期免疫排斥反应。结论：角质形成细胞和成纤维细胞与无细胞异种真皮基质构成的复合皮移植后能改善创面愈合质量,是一种较理想的、可探索的皮肤替代物。     

密闭性敷料与凡士林油纱对皮片供皮区创面愈区的比较研究

目的 观察密闭性敷料所造成的密闭液性环境对皮片供皮区创面愈合的影响。方法 以成人断层皮片供皮区创面为研究对象,采用自身对照法,应用临床观察、组织学、组织化学及电镜观察等方法。结果 密闭环境下创面愈合较快,其炎症反应较重,巨噬细胞出现较早较多,持续时间较长。结论 密闭环境下创面愈合早期的炎症反应较重,巨噬细胞出现较早较多,与促进创面愈合有关。     

Suprathel, a new skin substitute, in the management of donor sites of split-thickness skin grafts: results of a clinical study

OBJECTIVE: A prospective, randomized, two center clinical study was conducted to evaluate the impact on wound healing of Suprathel in donor sites of split-thickness skin grafts. Suprathel represents an absorbable, synthetic wound dressing with properties of natural epithelium. METHODS: 22 burn patients who were treated with split-thickness skin grafts, and with a mean age of 39.6 years were included in the study. Donor sites of skin grafts were randomly selected; partly treated with Jelonet and partly treated with Suprathel. First gauze change was carried out the fifth day postoperatively followed by regular wound inspection until complete re-epithelization. The study focused on patient pain score, healing time, analysis of wound bed, ease of care, and treatment costs. RESULTS: There was no significant difference between the two materials tested regarding healing time and re-epithelization. There was a significantly lower pain score for patients treated with Suprathel (p=0.0002). Suprathel became transparent when applied and allowed close monitoring of wound healing. In contrast to Jelonet, Suprathel showed excellent plasticity with better attachment and adherence to wound surfaces. Throughout the healing process it detached from wounds without damaging the new epithelial surface. In addition, wound areas treated with Suprathel required less frequent dressing changes. It also demonstrated excellent ease of care. This, altogether with the significant pain reduction, presented a positive feedback by patients and healthcare professionals who both rated Suprathel as their treatment preference. Though Jelonet is more cost effective as dressing material, the study revealed an overall reduction in total treatment costs achieved with Suprathel. CONCLUSION: Suprathel represents a solid, reliable epidermal skin substitute with impact on wound healing, patient comfort and ease of care. The material effectiveness contributes to the reduction of overall treatment costs.     

The rate of re-epithelialization across meshed skin grafts is increased with exposure to silver

The objective in this study was to determine whether exposure to pure silver increases the rate of re-epithelialization across a partial thickness wound. A meshed skin graft, placed on an excised burn wound was used as a healing model. Methods: The rate of meshed skin graft epithelial closure on an exposed burn using a moist healing environment was shown. A moistened silver delivery system (Acticoat) was compared with a standard xeroform and eight ply gauze dressing continually moistened with a 0.01% neomycin and polymyxin solution (NP). Twenty burn patients with deep burns of over 15% of TBS were excised and grafted with 2:1 meshed grafts. One graft area was treated with the antibiotic solution and another with the silver delivery. The meshed graft was performed within 3 days of injury. Results: No infections were noted and quantitative swab cultures gave less than 10(2) bacteria in all cases at wound closure. At day 7, re-epithelialization was complete with silver and 55% closed with NP solution. Wound closure was complete in the NP solution group at day 10. Silver increased re-epithelialization rate by over 40%, a significant increase. Graft take was over 95% in both groups. Conclusion: Silver released in a moist wound surface environment significantly increases the rate of re-epithelialization compared to a standard antibiotic solution.     

Autologous skin transplantation: comparison of minced skin to other techniques

BACKGROUND: Skin grafting may be necessary to close nonhealing skin wounds. This report describes a fast and minimally invasive method to produce minced skin suitable for transplantation to skin wounds. The technique was evaluated in an established porcine skin wound healing model and was compared to split-thickness skin grafts and suspensions of cultured and noncultured keratinocytes. MATERIALS AND METHODS: The study included 90 wounds on 3 pigs. Fluid-treated full-thickness skin wounds were grafted with minced skin, split-thickness skin grafts, noncultured keratinocytes, or cultured keratinocytes. Controls received either fluid or dry treatment. The wound healing process was analyzed in histologies collected at Days 8 to 43 postwounding. Wound contraction was quantified by photoplanimetry. RESULTS: Wounds transplanted with minced skin and keratinocyte suspension contained several colonies of keratinocytes in the newly formed granulation tissue. During the healing phase, the colonies progressed upward and reepithelialization was accelerated. Minced skin and split-thickness skin grafts reduced contraction as compared to keratinocyte suspensions and saline controls. Granulation tissue formation was also reduced in split-thickness skin-grafted wounds. CONCLUSIONS: Minced skin grafting accelerates reepithelialization of fluid-treated skin wounds. The technique is faster and less expensive than split-thickness skin grafting and keratinocyte suspension transplantation. Minced skin grafting may have implications for the treatment of chronic wounds.     

Povidone-iodine ointment: no effect of split skin graft healing time

In major burns, local treatment of the split skin graft after a burn injury is important to prevent serious infectious complications. Topical burn wound therapy may improve the bacteriological condition of the wound, which in turn may improve the successful take of a skin graft. Delay of wound healing is an undesired side effect of these topical anti-microbial agents. It is known that povidone-iodine has many clinical advantages. In view of this, the total healing time of the freshly grafted burn wound was studied. In this prospective study, comparable areas of the same patient were treated with povidone-iodine ointment or with simple vaseline gauze. There was no statistical difference in the total wound healing time between the treated and the control group.     

Porcine dermal collagen as a wound dressing for skin donor sites and deep partial skin thickness burns

Collagen was extracted by pepsin digestion from porcine skin, and collagen membrane was prepared by salt precipitation. The porcine collagen membrane was evaluated as a burn wound dressing in deep partial skin thickness burn wounds in rats. Burn wounds, 4 × 4 cm, were inflicted by exposure of skin to 75°C for 15 s followed by de-epithelialization. Wound healing was assessed by planimetry of epithelialization on day 10 after injury. Open wounds exhibited 24 per cent of wound area re-epithelialized. Collagen membrane dressing significantly improved the healing to 69 per cent of wound area (P < 0.0001). In a completely separate experiment, the porcine collagen membrane was applied as a wound dressing to the donor sites of burn patients, and its effect on wound healing was compared with that of a petroleum jelly gauze dressing. The donor sites covered with petroleum jelly gauze had re-epithelialized by an average of 14.5 days (ranging from 13 to 16 days) after wounding. The wounds dressed with collagen membrane demonstrated a significant increase in the healing rate. Complete re-epithelialization was observed by 10.3 days (ranging from 10 to 12 days) after wounding (P < 0.0001).     

Characterization of a novel standardized human three‐dimensional skin wound healing model using non‐sequential fractional ultrapulsed CO2 laser treatments

Background and Objective

At present, there is no standardized in vitro human skin model for wound healing. Therefore, our aim was to establish and characterize an in vitro/ex vivo three‐dimensional (3D) wound healing model, which we employed to analyze the effects of dexpanthenol on wound healing and gene regulation.

Materials and Methods

The novel human 3D skin wound healing model using scaffold and collagen 3D organotypic skin equivalents was irradiated with a non‐sequential fractional ultrapulsed CO₂ laser. These standardized injured full‐thickness skin equivalents enable qRT–PCR, microarray, and histological studies analyzing the effect of topically or systemically applied compounds on skin wound healing.

Results

These human laser‐irradiated skin models were found to be appropriate for in vitro wound healing analysis. Topical treatment of skin wounds with a 5% dexpanthenol water‐in‐oil emulsion or two different 5% dexpanthenol oil‐in‐water emulsions clearly enhanced wound closure compared to laser‐irradiated untreated control models. To find out whether this positive effect is caused by the active substance dexpanthenol, laser‐irradiated skin models were cultured in calciumpantothenate containing medium (20 μg/ml) compared to skin equivalents cultured without calciumpantothenate. 3D models cultured in calciumpantothenate revealed considerably faster wound closure compared to the control models. Quantitative RT–PCR studies showed enhanced mRNA expression of MMP3, IL1α, keratin‐associated protein 4–12 (KRTAP4–12), and decreased expression of S100A7 in laser‐irradiated skin models cultured in medium containing calciumpantothenate.

Conclusion

This novel standardized human 3D skin wound healing model proves useful for topical pharmacological studies on wound healing and reveals new insights into molecular mechanisms of dexpanthenol‐mediated effects on wound healing. In addition, these novel 3D model systems can be used to monitor ex vivo effects of various laser systems on gene expression and morphology of human skin. Lasers Surg. Med. 47:257–265, 2015. © 2015 Wiley Periodicals, Inc.     

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.     

微粒皮移植治疗大面积深度烧伤后关节瘢痕挛缩的初步体会

目的 探讨大面积深度烧伤病人自体微粒皮与大张异体皮移植术治疗关节部位瘢痕挛缩的方法.方法 选择大面积深度烧伤后期瘢痕严重增生挛缩造成关节畸形而自体皮匮乏的病人11例,共31个关节,在全麻下切除部分瘢痕,彻底松解,矫正关节畸形,用微粒皮加异体皮覆盖创面,术后进行植皮区压迫和早期功能锻炼.随访12个月以上.通过术前、术后的皮肤外观、关节功能、组织学观察等进行效果评价.结果 微粒皮移植者皮肤外观及关节功能明显改善;组织学可见表皮较厚,部分可见表皮脚,真皮层较薄,胶原纤维排列较有规律.结论 微粒皮加大张异体皮移植术可用于治疗大面积深度烧伤病人关节部位瘢痕挛缩.     

Meshed unexpanded split-thickness skin grafting for reconstruction of penile skin loss

PURPOSE: Sheets of unmeshed, split-thickness skin grafts (STSGs) have been advocated in potent men with penile skin deficiency. Since the survival of sheet grafts is rarely 100% and the appearance of unexpanded 1:1 mesh grafts is quite good, we used this technique. We report our experience with meshed, unexpanded STSGs for all penile resurfacing regardless of erectile function. MATERIALS AND METHODS: Nine consecutive patients with penile skin loss were prospectively treated between March 2001 and January 2003 with meshed STSGs to the penis. The underlying condition was Fournier's gangrene in 4 cases, chronic lymphedema in 2, skin deficiency from prior surgeries in 2 and Crohn's disease in 1. Graft thickness was 0.012 or 0.016 inches and meshing was performed in a 1:1 ratio. Meshed slits were oriented transversely without expansion and the graft juncture was located on the ventral surface in zigzag fashion. Graft take, appearance, and sexual and voiding function were assessed postoperatively. RESULTS: All 9 patients had 100% graft take. At a mean followup of 6 months a satisfactory cosmetic outcome was documented photographically in all except 1 case involving chronic penile manipulation. Erectile function and ejaculation were preserved in potent patients. CONCLUSIONS: Unexpanded meshed STSGs of penile skin loss yielded satisfactory functional and cosmetic outcomes.     

Methods of burn treatment. Part II: Technical aspects]

The best treatment for burns and scalds depends on the depth of the skin necrosis. Epidermal and superficial dermal burn injuries (IIa) can heal spontaneously with conservative treatment without scar development, but deep dermal or full-thickness burns constitute an absolute indication for surgery. Full-thickness or split-thickness skin grafts are used for wound closure. In the case of extensive burn injuries allografts are used for temporary wound closure. In certain licensed laboratories autologous keratinocytes can be cultured for transplantation. In circumferential burn injuries affecting the extremities or the trunk the rigid eschar has to be incised to relieve the pressure behind it. Following a debridement conservative treatment of superficial dermal burns involving wound coverage with biosynthetic dressings or nanocristalline silver gauze dressings or use of special disinfecting ointments can be implemented.