Negative pressure wound treatment in a neonate with epidermolysis bullosa simplex severe generalized: A case report

Negative pressure wound treatment (NPWT) is very useful for the treatment of chronic or deep wounds and in the setting of skin grafting. Due to the need for adhesive dressings, this treatment is rarely attempted in patients with skin fragility secondary to hereditary epidermolysis bullosa (EB). We present a neonate with EB simplex, severe generalized in a critical clinical state where NPWT was successfully applied and describe the measures taken to avoid any further skin damage. This case is of clinical importance to physicians and health care staff treating patients with this rare disease where additional therapeutic measures for the treatment of chronic wounds are scarce.     

Treatment of chronic wounds with bone marrow-derived cells

BACKGROUND: Recent evidence indicates that bone marrow contains stem cells with the potential for differentiation into a variety of tissues, including endothelium, liver, muscle, bone, and skin. It may thus be plausible that bone marrow-derived cells can provide progenitor and/or stem cells to wounds during healing. Our objective in this study was to establish proof of principle that bone marrow-derived cells applied to chronic wounds can lead to closure of nonhealing wounds. We applied autologous bone marrow cells to chronic wounds in 3 patients with wounds of more than 1-year duration. These patients had not previously responded to standard and advanced therapies, including bioengineered skin application and grafting with autologous skin. OBSERVATIONS: Complete closure and evidence of dermal rebuilding was observed in all patients. Findings suggesting engraftment of applied cells was observed in biopsy specimens of treated wounds. Clinical and histologic evidence of reduced scarring was also observed. CONCLUSION: Directly applied bone marrow-derived cells can lead to dermal rebuilding and closure of nonhealing chronic wounds.     

Recessive epidermolysis bullosa dystrophicans (Hallopeau-Siemens)--improvement of wound healing by autologous epidermal grafts on an esterified hyaluronic acid membrane.

Epidermolysis bullosa dystropicans of the Hallopeau-Siemens type (HS-EBD) is an autosomal-recessive blistering disease. Skin fragility due to mutations in structural proteins is responsible for further development of chronic and painful wounds, skin infections and sepsis. There is no causative treatment available. We present a case report with HS-EBD and longstanding painful wounds treated with autologous keratinocytes on an esterified hyaluronic acid membrane. Two out of three wounds treated showed a complete take of the graft. They improved markedly with a stable result over 12 months until now. Even autologous keratinocyte grafting may have a beneficial effect on chronic wounds in HS-EBD despite the fact that the genetic defects are unchanged.     

Skin grafts as pharmacological agents: pre-wounding of the donor site

Summary Initially thought to act as tissue replacement, cultured epithelial allografts arc now known to work by providing a potent stimultis for healing. In a similar fashion, we believe that traditional autografts may also provide a stimulus to help heal chronic wounds, thus acting as pharmacological agents for healing. We attempted to assess the possibility of augmenting the stimulatory properties of donor skin by initiating the healing process in the donor region prior to grafting. This was accomplished by pre-wounding the donor area 3 days prior to harvesting the donor skin. We compared these 'pre-wounded' grafts to those harvested immediately. Two patients underwent punch grafting for chronic leg ulceration. Half of the ulcer was grafted with donor skin harvested from an area that was pre-wounded and the other half from freshly harvested skin. We evaluated each for improvement of granulation tissue and degree of edge effect (migration ofthe previously dormant wound edges). All the grafts did well. There was marked improvement in granulation tissue in the ulcer hed after grafting, and the obvious presence of an edge effect. The edge eflect vvas increased on the site where the pre-wounded grafts were placed. It may be possible to augment the growth stimulatory properties of donor skin. This may offer therapeutic options in patients with chronic wounds.     

Tissue-engineered skin in the healing of wound stumps from limb amputations secondary to purpura fulminans

Currently wound treatment options of amputation stumps due to purpura fulminans include healing by secondary intention from wound debridement, split-thickness skin grafting, tissue and muscle flaps, plantar skin free transfer, skin expansion, artificial skin, and hyperbaric oxygen therapy. We saw a 6-month-old girl with purpura fulminans as a complication of meningococcemia. She developed necrosis of the distal extremities resulting in bilateral amputation of the lower limbs. Shortly thereafter the leg stumps also became necrosed and she underwent unsuccessful split-thickness grafts of lower limb ulcers. The patient's difficult-to-heal wounds made her an excellent candidate for treatment with tissue-engineered skin. At 10 months of age, this was applied to her previously nonhealing wounds. The tissue-engineered skin induced rapid healing of the patient's chronic amputation stump ulcers and provided her with substantial pain relief. In conclusion, tissue-engineered skin appears to be a potential beneficial treatment for chronic wounds in children with nonhealing amputation stumps.     

Grafting of skin ulcers with cultured autologous epidermal cells

We treated five adult individuals with six full-thickness chronic ulcerations in the skin caused by venous insufficiency, sickle cell anemia, or surgical wounds. Each patient received applications to the ulcerations of sheets of autologous epidermal cells grown in culture. All patients experienced relief of pain after grafting. Four of the six ulcers healed completely in 21 to 35 days, and three of the four remained healed for up to 2 years. One ulceration recurred within 2 months. Our experience suggests that cultured autologous epidermal grafts can provide continuous covering, relief from pain, and rapid healing of chronic debilitating ulcerations of the skin.     

Meek植皮术在大面积烧伤创面中的临床应用及护理研究

目的探讨Meek植皮技术治疗大面积烧伤创面的手术配合及护理体会。方法对28例大面积烧伤创面行Meek植皮术的术前准备、术中配合进行分析。结果Meek移植皮片全部存活，愈合质量高，治疗效果满意。结论大面积烧伤创面Meek植皮术，可以提高自体皮使用率和改善植皮区愈后，减少患者住院时间，降低经济费用，是大面积烧伤治疗中较为理想的植皮方法之一。手术室护士必须熟练掌握Meek植皮技术的操作方法及要点，积极配合手术，保证手术的顺利进行。     

One‐stage reconstruction of deep facial defects with a single layer dermal regeneration template

Background The reconstruction of deep facial wounds in oncological surgery is challenging. Especially for elderly multimorbid patients, a rapid procedure with acceptable aesthetic and reliable functional outcome is required. Recently, a new single layer skin substitute was developed. Integra^® dermal regeneration template single layer (IDRT‐SL) allows one‐stage surgery in combination with split thickness skin grafting. However, no study has yet analysed the efficiency of IDRT‐SL treatment. Objectives To evaluate applicability and efficiency of the IDRT‐SL treatment in combination with split thickness skin grafting for a one‐step closure of deep facial surgical wounds in elderly multimorbid patients. Patients/Methods This prospective study analysed the functional and aesthetic outcome after reconstruction with an IDRT‐SL template and an immediate split thickness skin graft in the face (80 ± 3 years; >3 concomitant diseases). Results Nine tumours, four basal cell carcinoma, two lentigo maligna, one spinal cell carcinoma, one lentigo maligna melanoma and one Bowen carcinoma were resected. Five defects were located on the nose and four on the cheek. The mean defect size was 11 ± 3 cm². All but one graft were taken completely without any complication. One patient suffered from a partial graft loss (30%). All defects showed significant shrinkage of 61 ± 4%. Conclusions One‐stage reconstruction with a combination of IDRT‐SL and split thickness skin grafting is an elegant, easy and rapid method to treat deep skin defects. The take rates, functional and early cosmetic outcome are promising. This new method should be considered for selected cases of elderly multimorbid patients with deep facial wounds.     

The Effect of a Collagenous Implant on Deep Dermo-Periosteal Defects in the Rabbit

In plastic surgey, extensive wounds with exposed bone and loss of the periosteum (i.e., deep dermo-periosteal defects) are difficult to treat, even with split-thickness skin grafts, because such grafts rarely survive. Even when these grafts do survive, functional impairment often occurs subsequently. The application of a collagen sponge (Terudermis®, Terumo, Tokyo) to such wounds has previously been reported to accelerate granulation tissue formation, resulting in would healing and graft survival. However, this previous report only presented data relating to gross morphological appearance In this paper, we present histological evidence to demonstrate the beneficial effect of the collagen sponge on experimental dermo-periosteal scalp defects in rabbits. About two weeks after the application of collagen sponge to the experimental wounds, a well-vascularized granulation tissue was formed. Autologous split-thickness skin grafts applied to this new granulation tissue were found to be viable one week after grafting. The results confirm histologically that collagen sponge is effective for the treatment of deep dermo-periosteal defects which would not have regenerated skin cover with conventional therapies such as skin grafting or the temporary use of dermoprotective materials followed by skin grafting.     

Organotypic keratinocyte coculture using normal human serum: an immunomorphological study at light and electron microscopic levels

Organotypic human skin equivalents of keratinocytes and fibroblasts embedded in collagen matrix have been the subject of studies dealing with various culture conditions. Development of standardized living skin equivalents using defined culture media containing respective supplements can provide important instruments of investigation in skin biology. In addition, tissue engineering has created human skin substitutes for treatment of acute and chronic wounds. In our study, we generate a modified organotypic human skin equivalent using normal human serum instead of fetal calf serum (FCS). This living skin equivalent shows regular stratification of the epidermis and the dermal-epidermal junction zone at the light and electron microscopic level after 1 and 3 weeks of coculture. Indirect immunofluorescence reveals regular expression of differentiation antigens and the major structural proteins collagen IV, laminin 5 and the integrin chains alpha 6 and beta 4 at the dermo-epidermal junction zone. Immunoelectron microscopy demonstrates expression of collagen IV, alpha 6 and beta 4 integrin after 1 and 3 weeks of coculture. This organotypic skin model could be the basis for autologous skin grafting for acute or chronic wounds using autologous serum as well as patients' keratinocytes and fibroblasts, thus minimizing the risk of transmitting infectious agents.     

Wound bed preparation with 10-percent phenytoin ointment increases the take of split-thickness skin graft in large diabetic ulcers

Healing of large diabetic foot ulcers may be difficult, particularly if the blood supply and chronic infection do not allow primary suturing. Split-thickness skin graft is a simple reconstructive technique used to close large wounds. Phenytoin is known to promote healing mainly by increasing granulation tissue formation. The effectiveness of topical phenytoin in wound-bed preparation (WBP) for split thickness skin grafting has been examined in 16 patients with large diabetic foot ulcers. All patients were treated with standard wound bed preparation including debridement of necrotic tissue. Topical phenytoin (10 % w/w ointment) was applied for 2-8 weeks prior to performance of autografting. Clinical and histologic evaluations were performed. The graft survival was 100 percent In twelve patients, 80-90 percent in three patients take and 60 percent in one patient. Neither local nor systemic side effects were observed. The authors conclude that phenytoin ointment is a safe and efficacious treatment to enhance the survival of split-thickness skin grafts in large chronic diabetic ulcers.     

Epithelial-mesenchymal interactions in wounds: treatment of palmoplantar wounds by nonpalmoplantar pure epidermal sheet grafts

BACKGROUND: Palms and soles differ from other body sites in terms of clinical and histologic appearance and response to mechanical stress. We previously reported that palmoplantar fibroblasts regulate keratin 9, which is a marker of palms and soles. OBJECTIVE: To treat palmoplantar wounds by using nonpalmoplantar pure epidermal sheets as a graft. DESIGN: Nonrandomized controlled trials. SETTING: University dermatology and plastic surgery services. PATIENTS: Forty-eight patients with palmoplantar wounds caused by burns, trauma, chronic ulcers, and the resection of malignant tumors, such as squamous cell carcinoma and acral lentiginous melanoma. INTERVENTIONS: The patients received nonpalmoplantar pure epidermal sheet grafts (n = 14), nonpalmoplantar donor site skin grafts (n = 17), or palmoplantar donor site skin grafts (n = 17). MAIN OUTCOME MEASURES: Clinical and histologic findings. RESULTS: The pure epidermal sheets were successfully grafted and gradually demonstrated the adoption of a palmoplantar phenotype when reticular dermis of the recipient site remained. The epidermis showed hyperkeratosis and acanthosis by histologic studies and stained positively for keratin 9 in all of the suprabasal keratinocyte layers like palmoplantar-type skin. Pure epidermal sheets were placed on deeper wounds after the wounds had an artificial dermis applied and adopted the palmoplantar phenotype without erosions and ulcerations. Neither nonpalmoplantar split-thickness nor full-thickness skin grafts resulted in a palmoplantar phenotype. CONCLUSIONS: Pure epidermal sheet grafting would be useful for the treatment of palmoplantar wounds as nonpalmoplantar epidermis is much easier to obtain clinically. In addition, secondary procedures are not required to repair the donor site, since this wound is superficial.     

Purified Type I Collagen Wound Matrix Improves Chronic Wound Healing in Patients with Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa is a severe genetic blistering skin condition resulting in chronic wounds. Nonhealing wounds were treated over 8 weeks using a reconstituted natural purified type I collagen skin substitute. Chronic wounds were defined as nonhealing wounds present for longer than 6 months. For each patient, two chronic wounds were identified and randomized into a control or treatment group. Both groups received standard‐of‐care wound dressings. The treatment group received an additional type I collagen skin substitute. Wound size was measured at baseline and weeks 1, 4, and 8. Pain, pruritus, and burning and stinging were assessed. Wound cultures were obtained at baseline and thereafter as was considered clinically relevant. Ten subjects were enrolled; seven completed the study. Six subjects showed a positive response to the type I collagen skin substitute. Three subjects demonstrated full wound reepithelialization. Wounds treated using the collagen skin substitute showed statistically significantly greater improvement. Average scores for pruritus and pain decreased significantly. Reconstituted natural purified type I collagen skin substitutes improved the healing of chronic wounds and may be a valuable addition to the epidermolysis bullosa wound care arsenal.     

An allogeneic cultured dermal substitute suitable for treating intractable skin ulcers and large skin defects prior to autologous skin grafting: three case reports

Intractable skin ulcers that arise as secondary lesions from disease and full-thickness skin defects that result from skin tumor excision often need autologous skin grafting to close the wound. We developed an allogeneic cultured dermal substitute (CDS) to shorten the time needed to prepare a wound bed suitable for autologous skin grafting. The CDS was prepared by plating normal human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelo-collagen. The allogeneic CDS was then placed on the rinsed wound surface. This procedure was repeated twice a week for up to five weeks, until the wounds were closed by autologous skin grafting. In all three cases, after CDS treatment for two to five weeks, the wound conditions became suitable for skin grafting; these conditions had not been improved by conventional topical treatments, including topical basic fibroblast growth factor (bFGF). Healthy granulation tissue developed rapidly, concomitant with wound size reduction. The present results indicate that CDS is an excellent biological wound dressing for improving wound conditions so that they are suitable for subsequent autologous skin grafting as well as for shortening the treatment duration for skin ulcers and full-thickness skin defects.     

Altered expression of L-arginine metabolism pathway genes in chronic wounds in recessive dystrophic epidermolysis bullosa

Individuals with the severe, mutilating Hallopeau-Siemens form of recessive dystrophic epidermolysis bullosa (HS-RDEB) have trauma-induced blisters and skin erosions which often progress to wounds that are slow to heal. These chronic wounds cause considerable morbidity and there is an increased risk of squamous cell carcinoma arising in the wound margins. Currently, little is known about the keratinocyte cell biology in these wounds. Therefore, we compared the gene expression profiles of wound edge with nonwounded skin from two individuals with HS-RDEB. Trauma-induced wound sites had been present in both patients for more than 3 months. Hybridizations using DermArray gene expression filters showed relative differences in gene expression between wounded and unwounded skin. Notably, there was a fivefold increase in expression of arginase-1 (ARG1) in the chronic wound samples. Expression of seven other genes relevant to L-arginine metabolism also showed differences greater than twofold. L-arginine is known to have a critical role in the synthesis of nitric oxide as part of normal tissue repair. Although alterations in arginase isoenzymes have been detected previously in other chronic wounds (human and animal models), this is the first study to demonstrate differences in several components of the L-arginine metabolism pathway in chronic wounds, and the first to examine chronic wounds in HS-RDEB. The data show that the cascade of L-arginine metabolites is altered in HS-RDEB and the findings may provide new insight into the pathology of chronic wounds in this genodermatosis.     

Contact sensitization in patients with chronic wounds: Results of a prospective investigation

Background It is well known that patients with chronic wounds frequently acquire clinically relevant contact sensitizations to skin care products. Objectives The aim of our study was to find out the actual frequency of contact sensitivities in patients with chronic wounds in Germany with particular attention to components of products used in modern wound therapy. Methods We examined the results of a prospective clinical investigation on skin patch tests of patients with chronic wounds. Results Altogether, 45 patients with chronic wounds were tested. In 25 (55.5%) of the examined patients, contact sensitization to at least one substance was detected. The most frequent contact sensitizations were to PVP‐iodine (20%), balsam of Peru (15.6%) patients, fragrance mix (11.1%), colophony (8.8%) and potassium dichromate (6.7%). We also found sensitization to the wound dressings Varihesive? (11.1%), Iruxol? N (6.7%) and Comfeel? (2.2%). Conclusions We would like to propagate that therapists who are involved in wound treatment should also pay attention on the ingredients of applied modern wound dressings.     

Wounds and malignancy

Due to the prevalence of skin cancers, health care practitioners involved with wound management are likely to encounter cutaneous malignancies as part of their practice. This article focuses on 2 ways in which malignancies and wounds are related: the malignant degeneration of chronic wounds into cancer and malignancies that present as chronic wounds. The most common scenario in which chronic wounds have been associated with the development of squamous cell carcinoma is in the presence of chronic osteomyelitis. However, wounds secondary to burns, trauma, radiotherapy, and diabetes are also at risk for malignant degeneration. It is often difficult to distinguish malignant transformations from primary malignant ulcers. Given the uncommon nature of degeneration of a chronic wound or a malignancy presenting as a chronic wound, some suggest that only suspicious wounds undergo biopsy. Primary malignancy should be considered if the ulcer has a relatively short duration and the patient does not have a history of prior radiotherapy. Until recently, amputation has been the treatment of choice for squamous cell carcinomas that arose within chronic wounds associated with chronic osteomyelitis; however, other reports have shown that other methods of ensuring complete local excision are also useful.     

Rapid healing of intractable diabetic foot ulcers with exposed bones following a novel therapy of exposing bone marrow cells and then grafting epidermal sheets

BACKGROUND: Diabetic foot ulcers with exposed bones commonly result in amputation. OBJECTIVES: To determine whether exposure of bone marrow cells and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation. METHODS: Thirty-eight patients with chronic wounds caused by diabetes mellitus were enrolled in this study. Epidermal sheets obtained from suction blisters of each patient were grafted on to diabetic foot ulcers without exposed bones (n = 10) and were compared with the standard treatment of local wound care, debridement with a scalpel when indicated, bed rest and parenteral antibiotics (n = 8). In another group of patients, diabetic wounds with exposed bones were treated either with the standard procedure (n = 9) or with a newly developed experimental procedure (n = 11). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until fresh bleeding was observed from the exposed bone. The lesions were then immediately covered with an occlusive dressing, and finally the wound was covered with an epidermal graft of skin harvested from suction blisters. Patients in each group were matched with their counterparts by age, sex, wound size, wound infection and wound duration, to compare the time needed for total skin repair and rates of amputation. RESULTS: Epidermal grafting significantly accelerated the healing of diabetic foot ulcers (P = 0.042) without exposed bones, with site-specific differentiation. The newly developed combination therapy resulted in the healing of all diabetic ulcers with exposed bones without the occurrence of osteomyelitis or the necessity for amputation (P < 0.0001). CONCLUSIONS: Our study indicates that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation.     

A modified, improved, easy and fast technique for split-thickness skin grafting

Background Large nonhealing ulcers and wounds frequently pose a great therapeutic challenge to clinicians and often require skin grafting. Various skin grafting methods are available to cover large skin defects that fail to epithelize. These methods include the use of small pinch grafts, full‐thickness punch grafts, large‐sized full‐thickness grafts and split‐thickness grafts. Large‐sized full‐thickness and split‐thickness skin grafting requires expertise to produce cosmetically acceptable results and prevent cobblestoning, unlike small pinch and full‐thickness punch grafts. Objectives To describe a modified technique of split‐thickness skin grafting that can be considerably faster than alternative methods. Methods We describe a method for split‐thickness skin grafting using tumescent anaesthesia at the donor site and an electrodermatome and a polyurethane membrane without sutures at the site of the skin defect. Results Since 1997, we have practised a modified, improved, quick and easy split‐thickness skin grafting method to cover large skin defects at the extremities. Complete healing is usually achieved 4–6 weeks after the split‐thickness skin transplantation, and long‐term results are aesthetically successful. Conclusions We provide a sophisticated modified split‐thickness skin graft procedure that has been practised for many years and provides cosmetically acceptable results while saving time.     

Transplantation of autologous single hair units heals chronic wounds in autosomal recessive dystrophic epidermolysis bullosa: A proof-of-concept study

Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is characterized by recurrent mucocutaneous blistering with non-healing ulcers which are often complicated by squamous cell carcinoma (SCC). Despite having as high as 80% death rate from SCC, RDEB still does not have an effective treatment. We report on the efficacy of single follicular unit extract (FUE) grafting to heal chronic ulcers of intermediate RDEB in a 54-year-old woman with extensive chronic wounds covering around 30% of the body surface area. On Day 17 post first graft session, the area of treated ulcers on her right upper back was reduced by 80%. Immunofluorescence study revealed positive type VII collagen expression along the epidermal and follicular basement membrane zone in the donor and recipient sites. A few grafted follicles continued to grow hair on the recipient sites. A total of 360 FUEs were grafted in nine sessions over five years, resulting in healing of most treated ulcers and reduced significantly her time for daily wound dressing. Importantly, FUE grafting using patient's own scalp follicles does not require any laboratory manipulation. It is safe and easy to perform. Autologous follicular grafting appears efficacious for healing of recalcitrant wounds and provides an innovative solution for RDEB patients with such wounds.