Graftskin Treatment of Difficult to Heal Diabetic Foot Ulcers: One Center''s Experience

BACKGROUND: Chronic diabetes-related foot ulcers result from predisposition, tissue injury, and inadequate reparative mechanisms. Standard care for diabetes-related foot ulcers includes weight off-loading, pressure-relieving footwear, aggressive surgical debridement, and frequent dressing changes. Graftskin is a recently developed living skin construct. OBJECTIVE: To compare Graftskin and standardized wound care to standardized wound care alone in the treatment of difficult to heal diabetes-related neuropathic foot ulcers, and to assess the handling and application characteristics of Graftskin. METHODS: A university dermatology clinic was part of a 24-center prospective, randomized, controlled, parallel group comparative trial of Graftskin for the treatment of difficult to heal neuropathic diabetes-related foot ulcers. Patients were randomly assigned to treatment with Graftskin with aggressive debridement and standardized wound care, or aggressive debridement and standardized wound care alone. Blinding was not feasible due to device visibility during application. RESULTS: Five of nine patients (56%) treated with Graftskin therapy had complete healing. Three of eight control patients (37%) had complete healing. CONCLUSION: Graftskin as an adjunct to aggressive debridement and standardized wound care appears to be a valuable treatment adjunct in patients with difficult to heal diabetes-related neuropathic foot ulcers. The application learning curve was steep and the ease of application exceptional.     

Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing

HYPOTHESIS: In patients with diabetic foot and pressure ulcers, early intervention with biological therapy will either halt progression or result in rapid healing of these chronic wounds. DESIGN: In a prospective nonrandomized case series, 23 consecutive patients were treated with human skin equivalent (HSE) after excisional debridement of their wounds. SETTING: A single university teaching hospital and tertiary care center. PATIENTS AND METHODS: Twenty-three consecutive patients with a total of 41 wounds (1.0-7.5 cm in diameter) were treated with placement of HSE after sharp excisional debridement. All patients with pressure ulcers received alternating air therapy with zero-pressure alternating air mattresses. MAIN OUTCOME MEASURE: Time to 100% healing, as defined by full epithelialization of the wound and by no drainage from the site. RESULTS: Seven of 10 patients with diabetic foot ulcers had complete healing of all wounds. In these patients 17 of 20 wounds healed in an average of 42 days. Seven of 13 patients with pressure ulcers had complete healing of all wounds. In patients with pressure ulcers, 13 of 21 wounds healed in an average of 29 days. All wounds that did not heal in this series occurred in patients who had an additional stage IV ulcer or a wound with exposed bone. Twenty-nine of 30 wounds that healed did so after a single application of the HSE. CONCLUSIONS: In diabetic ulcers and pressure ulcers of various durations, the application of HSE with the surgical principles used in a traditional skin graft is successful in producing healing. The high success rate with complete closure in these various types of wounds suggests that HSE may function as a reservoir of growth factors that also stimulate wound contraction and epithelialization. If a wound has not fully healed after 6 weeks, a second application of HSE should be used. If the wound is not healing, an occult infection is the likely cause. All nonischemic diabetic foot and pressure ulcers that are identified and treated early with aggressive therapy (including antibiotics, off-loading of pressure, and biological therapy) will not progress.     

Efficacy of allogeneic cord blood platelet gel on wounds of dystrophic epidermolysis bullosa patients after pseudosyndactyly surgery

Epidermolysis bullosa (EB) is a rare genetic disorder characterized by the formation of blisters and wounds in skin and mucous membranes; it is classified into four types and has various methods of treatment. Management of previous wounds and prevention of formation of new lesions are the most important strategies in the course of therapy to improve patient's quality of life; lack of wound management can lead to further complications such as infection. The current study investigated the therapeutic effects of allogeneic platelet gel (prepared from umbilical cord blood) in a group of children diagnosed with dystrophic epidermolysis bullosa (DEB) eligible for surgical correction of pseudosyndactyly in the hand. The post‐surgical clinical outcome in this group was compared with the clinical outcomes of DEB patients receiving the standard treatment (paraffin gauze wound dressing and topical antibiotics) after corrective surgery. The current study results showed an increase in the rate of recovery and promotion of tissue granulation, complete wound healing, and a decrease in pain level and treatment period. The application of cord blood platelet gel topical dressing was not a conventional method of treatment in patients with DEB wounds and blisters. However, the current study results demonstrated that this gel dressing could effectively accelerate epithelialization and healing of the wounds and decrease patients' pain and post‐surgical recovery period, which altogether leads to improvements in patients' overall quality of life.     

Delayed Staged Closure With Repeated Directional Suturing of Cutaneous Defects

BACKGROUND: Postsurgical wound management is traditionally a choice between intraoperative surgical repair or healing by secondary intention. We describe a technique that combines intraoperative and postoperative surgical repair with granulation. OBJECTIVE: Delayed closure with repeated directional suturing was evaluated as an alternative closure technique for large wounds. METHODS: Sixty patients had surgical defects partially closed intraoperatively with postoperative staged closures over 2 to 4 weeks. Only those wounds that could not be closed intraoperatively without vascular compromise or anatomic disfigurement were treated. RESULTS: All wounds were closed using skin from the same anatomic unit. Complications were minimal, and the results were acceptable to both the patients and the surgeon. CONCLUSION: Delayed closure with repeated directional suturing is a reasonable alternative when primary closure is not possible or when it would cause anatomic disfigurement.     

A bilayered living skin construct (APLIGRAF®) accelerates complete closure of hard-to-heal venous ulcers

The efficacy of a bilayered, living skin construct (APLIGRAF(R) [Graftskin]) was evaluated in patients (n = 120) with hard- to-heal venous leg ulcers of greater than 1 year's duration. The study was prospective, randomized, and controlled. Patients received Graftskin plus compression therapy, or standard compression therapy (active control). Patients were evaluated for frequency and time to complete (100%) wound closure. Treatment with Graftskin was significantly more effective than active control in the percentage of patients healed by 6 months (47% vs. 19%; p < 0.005) and the median time to complete wound closure (p < 0.005). Analysis with multivariate regression methods, adjusting for factors generally thought to influence wound healing (duration, baseline area, depth, location, fibrinous wound bed, and infection), showed that patients treated with Graftskin were twice as likely to achieve complete wound closure by 6 months (p < 0.005), and over 60% more effective in achieving wound closure than active control (p < 0.01). These data indicate that Graftskin is an effective treatment for venous ulcers of greater than 1 year's duration.     

Management of wounds with exposed bone structures using an artificial dermis and skin grafting technique

The task of managing an open wound complicated by exposed bony structures underneath is difficult, if not challenging. We have instituted a method of managing the problems in stages using an artificial dermis and skin grafting technique in 17 wounds in 15 individuals from Sept. 2006 to Feb. 2009. While all wounds were noted to assume aberrant healing processes, the majority of involved bony structures were devoid of periosteal covering compounded by various degrees of infection. Of 15 incidents, mechanical trauma was responsible for 10, chemical burns for two and electrical burns for two patients. A chronic non-healing ulcer with exposed bone formed in an old burn scar accounted for the remaining one. The regimen of surgical management consisted of initial debridement, the coverage of the resultant wound with an artificial dermis and a partial-thickness skin grafted over this dermis-like structure grown with granulation tissues. Complete wound healing was attained in 15 out of 17 with outstanding cosmetic and minimal donor-site morbidity. Despite initial failure encountered in two, the morbidities noted were low. It is especially useful in large defects that usually require flaps for coverage.     

Cultured epithelial autografts for the coverage of large wounds: minimizing skin graft donor sites in the sick patient

Systemically unwell patients with extensive wounds present a reconstructive challenge. Conventional skin grafting results in surgical morbidity and donor wounds that may not heal. We propose that cultured skin, in the form of cultured epithelial autografts, be used for wound coverage in these patients. We present two patients with chronic large wounds over the abdomen and the leg. Keratinocytes obtained from a skin biopsy were cultured on a fibrin mat and the cultured epithelial autograft (CEA)–fibrin construct was delivered onto the wound bed 3 weeks later. Initial graft take was 85 and 75 % respectively, and epithelization was complete by 3 weeks. Stable, good quality coverage was maintained at 1.5 years follow-up. We conclude that in a selected group of patients, CEA is a useful modality for the reconstruction of extensive defects with minimum donor site morbidity. The fibrin mat is an optimal system that supports the growth of keratinocytes and allows easy delivery to the wound bed. Level of Evidence: Level IV, therapeutic study.     

032 Treatment of Chronic Ulcer with Allogeneic Cultured Dermal Substitute (CDS) composed of Collagen Sponge with Fibroblasts

We have been cultivating human epidermal cells for therapeutic purpose according to the original methods developed by Rheinwald and Green. Cultured epithelium (CE) was applied to patients with severe skin defects, burn wounds, chronic skin ulcers and cutaneous disorders like hypomelanosis. Autologous CE allows to restore massive skin surface in a short period compared with other conventional treatments. For grafts take, it is important to manage wound beds properly prior to CE grafting. The CDS was applied to prepare wound bed acceptable for CE grafting. The CDS was designed to secrete various types of cytokines, i.e., VEGF and KGF to stimulate wound healing. The successful management of deep wounds like chronic skin ulcer or burn ulcer requires granulation tissue formation and epithelialization to wound closure. This study aimed to evaluate the application of CDS in conjunction with CE for patients with chronic skin ulcer and burn ulcer. In some cases the wounds were cured by using CDS, and followed by CE grafting. All clinical trials achieved excellent or good results, showing no contracture and no hypertrophic scar after wound closure. The CDS was found to be useful to prepare wound beds and to facilitate wound management.     

感染性股动脉假性动脉瘤手术治疗及伤口处理：附16例分析

目的:探讨感染性股动脉假性动脉瘤治疗的手术方式,以及评估封闭负压辅助闭合(VAC)装置在治疗感染伤口的作用和应用价值。方法:回顾性分析2015年7月—2018年4月行手术治疗的16例感染性股动脉假性动脉瘤患者的临床资料。结果:16例患者术中破损动脉直接缝合破口5例,自体静脉修补6例,自体静脉置换3例,2例行动脉瘤切除局部旷置。患者手术伤口术后均经VAC装置引流治疗;伤口二期直接缝合12例,行皮瓣移植4例,伤口愈合时间平均34.2 d。术后13例患者获随访6个月,除1例伤口再次破溃接受清创治疗之外,其余12例患者伤口均无再次感染或破溃,所有随访患者动脉瘤均未复发。结论:感染性股动脉假性动脉瘤应尽早手术清创治疗;VAC装置治疗感染性伤口安全、有效。     

Use of a lyophilized bovine collagen matrix in postoperative wound healing.

BACKGROUND: Immediate reconstruction is the preferred approach to the management of defects following Mohs micrographic surgery. In a minority of patients, however, reconstruction is contraindicated, and a long-term biological dressing that stimulates wound healing and minimizes wound care is desirable. OBJECTIVE: We wanted to assess the utility of a lyophilized, type I bovine collagen matrix (SkinTemp) in wound care and wound healing following Mohs micrographic surgery. METHODS: Fifteen patients were treated with a bovine collagen matrix following Mohs micrographic surgery. Study wounds were evaluated for time to complete granulation, time to complete epithelialization, and adverse reactions including infection and allergy. The time to complete healing (granulation and epithelialization) for this group was compared to 15 size- and site-matched surgical defects. RESULTS: The use of bovine collagen matrix provided more rapid wound healing than traditional second intention healing at all anatomic sites studied. The time to complete healing averaged 6.1 weeks with bovine collagen matrix versus 9.4 weeks for the control group. Use of bovine collagen matrix required an average of 3.0 dressing changes weekly compared to 7.0 changes weekly in the control group. There were no wound infections or allergic reactions to it. CONCLUSIONS: A Type I bovine collagen matrix provided a safe, readily available alternative to traditional methods of second intention healing. It minimized wound care while reducing the time for complete healing. A larger study should be performed to confirm the results of this pilot study.     

Cold atmospheric plasma promotes different types of superficial skin erosion wounds healing

Superficial skin erosion wounds are very common in the clinic, and conventional treatments are not always effective; thus, effective and novel therapy is needed. Cold atmospheric plasma (CAP) has been recognised as a promising approach to wound healing. The purpose of this study is to show the potential clinical application of CAP for the healing of different kinds of superficial skin wounds. Seven patients with different kinds of superficial skin wounds (two patients with pyoderma gangrenosum, two patients with trauma would, one patient with giant genital wart, one patient with diabetic foot, and one patient with chronic eczema) were recruited to this study. All patients accepted and received CAP treatment every other day till the wound healed. The expected results were complete wound healing after CAP treatment. All patients achieved complete wound healing after several rounds (range from two to eight) of CAP treatment, and there was no side effect observed. CAP may provide a new and effective choice to solve the problem of the healing of superficial wounds that are not only caused by trauma but also because of eczema. CAP has certain value in the treatment of superficial skin diseases in the future.     

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.     

Vacuum-assisted closure: indications and clinical experience

The use of subatmospheric pressure to promote wound healing has gradually found support in the past few years. The vacuum-assisted closure system uses a pump providing a continuous negative pressure of preferably 125 mmHg, which is distributed over the wound surface by an airtight covered foam. The exact mechanisms of vacuum therapy are not yet understood, but clinically soft tissue defects seem to heal faster when subatmospheric pressure is applied. Our experience with the first 100 patients with soft tissue defects of different origin that were treated with vacuum therapy is presented. In 29 patients, the wounds healed without further surgical intervention, 53 patients underwent secondary wound closure and 11 patients required more than one procedure. Seven patients died due to their underlying disease. Few complications were seen. Vacuum sealing is a new therapeutic concept in wound healing which can precede and sometimes replace surgical wound closure. Received: 18 January 2000 / Accepted: 9 February 2000     

An economic assessment of Apligraf® (Graftskin) for the treatment of hard-to-heal venous leg ulcers

Several recent advances in wound care may offer promise for the treatment of hard-to-heal venous leg ulcers. One such treatment is Apligraf (Graftskin), a bilayered, living human skin construct. To assess the economic impact of Graftskin, a model was constructed to compare the annual medical costs and cost-effectiveness of treating hard-to-heal venous leg ulcers with Graftskin vs. compression therapy using Unna's boot. A semi-Markov model was used to describe the pattern of ulcer treatment, healing, and recurrence among patients with venous leg ulcers. Patients received 1 of 2 treatment regimens, Graftskin or Unna's boot, and were followed in the model for a 12-month period. The analysis was done from the perspective of a commercial health plan; therefore, only direct medical costs were included. Health care resource use included the primary therapeutic intervention, additional compression dressings, physician office visits, home health visits, laboratory tests and procedures, management of adverse events, and hospitalizations. The model estimated the annual medical cost of managing patients with hard-to-heal venous leg ulcers to be $20,041 for those treated with Graftskin and $27,493 for those treated with Unna's boot. In addition, treatment with Graftskin led to approximately 3 more months in the healed state per person per year than did treatment with Unna's boot. Because patients treated with Graftskin experienced improved healing compared with those treated with compression therapy using Unna's boot, they required fewer months of treatment for unhealed ulcers. As a result, the use of Graftskin for treating hard-to-heal venous leg ulcers resulted in lower overall treatment costs.     

Artificial Skin for Closure and Healing of Wounds Created by Skin Cancer Excisions

BACKGROUND: A dermal regeneration template indicated for life-threatening third-degree burn injuries is a product with potential application to smaller wounds to aid in healing and closure of complex excision sites. OBJECTIVE: To assess the effectiveness of dermal regeneration template for closure of skin cancer excision sites that would have otherwise required complicated closures. METHODS: Five patients, 61-84 years old, with skin cancer surgery yielding a total of six wounds were treated with the dermal regeneration template to close and heal their wounds. RESULTS: Four of five patients had complete healing (five of six wounds) with cosmetically acceptable results. The one treatment failure was application of the dermal regeneration template over exposed skull where inadequate neodermis formed. Successful healing was observed in five complex skin cancer excision sites including two wounds in previously irradiated grafted skin, a large and deep temporal defect, a wide excision in the supraclavicular region, and an excision down to cartilage on the antihelix of the ear. No infections were noted, although in four of five patients prophylactic oral antibiotics (either erythromycin or cephalexin) were prescribed postoperatively for 1-2 weeks. CONCLUSION: The product simplified wound care, subjectively appeared to decrease pain and postoperative bleeding, and yielded cosmetically acceptable wound repair. Autografting was not necessary; wounds healed in 2-4 months by epithelialization over neodermis after removal of the silicone layer. Furthermore, the product was a convenient long-term dressing and healing device for wounds where complex repairs, autografts, and/or flaps would otherwise be considered for closure.     

Wound healing and all‐cause mortality in 958 wound patients treated in home care

Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound‐healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all‐cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home‐care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow‐up on December 2012. In total, 958 consecutive patients received wound care by home‐care nurses, corresponding to a 1‐year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50–3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03–0.50; pressure vs. other wounds: AHR 0.44, 0.27–0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35–7.50; pressure vs. other wounds: AHR 2.91, 1.56–5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis.     

Hyaluronic acid derivatives and their healing effect on burns,epithelial surgical wounds,and chronic wounds: A systematic review and meta‐analysis of randomized controlled trials

Hyaluronic acid (HA) is a polysaccharide common to most species and is found in many sites in the human body, including the skin and soft tissue. A systematic review of the literature and meta‐analysis was performed to identify randomized controlled trials, evaluating the use of HA derivatives in healing burns, epithelial surgical, and chronic wounds. Nine studies were identified, which met the search criteria and clinical endpoints of complete healing and percent wound size reduction when using HA vs. either an active or passive comparator. It was found in the vast majority of randomized controlled trials (eight of nine) that HA derivatives significantly improved the healing of wounds vs. traditional therapies or placebo (either via complete healing or a significant reduction in wound size) occurring from burns, venous insufficiency, diabetes, neuropathic insufficiency, and surgical removal of the epithelial layer (for tattoo removal). In the other remaining trial, one formulation of HA was compared with another, with the higher concentration showing improved application characteristics. Further, it was found in a meta‐analysis in subsets of patients with diabetic foot ulcers (neuropathic) that HA derivatives healed these types of wounds significantly faster than standard of care. These studies in aggregate show that HA derivatives accelerate the healing process in burns, epithelial surgical wounds, and chronic wounds.     

Healing of Refractory Sinus Tracts by Dermal Matrix Injection With Cymetra

BACKGROUND: Sinus tracts are difficult wounds where clinical evidence to direct management is lacking. Should medical therapy fail, surgical options focus on various flaps and tissue grafts. We report the successful use of a simple surgical procedure to promote healing in recalcitrant sinus tracts: the use of the dermal matrix substitute Cymetra (LifeCell Corp., The Woodlands, NJ). OBSERVATIONS: Two patients-one a woman with a chronic sacral decubitus and the other an older gentleman with pyoderma gangrenosum-each developed a sinus tract that was unresponsive to medical therapy. After use of Cymetra, both patients healed completely without adverse reaction. They remained ulcer free at 1-year follow-up. CONCLUSION: Cymetra, micronized decellularized cadaveric dermis, may have utility in repairing soft tissue defects and promoting wound healing. It offers a safe and effective alternative in the management of recalcitrant sinus tracts.     

Pelvic reconstruction using vertical rectus abdominis musculocutaneous flaps

Coverage of complex perineal wounds resulting from surgical and radiation therapy results in significant morbidity. Acute complications occur in 25% to 60% of patients. Serious complications occur in 25% to 46% of patients. Musculocutaneous or omental flaps are used as primary or salvage procedures for nonhealing perineal wounds. Vertical rectus abdominis flaps are ideally suited to bring nonirradiated tissue into defects associated with radical surgical extirpation procedures and irradiated fields.A retrospective review of 73 cases using a vertical rectus abdominis flap for perineal reconstruction is reported. Acute perineal wound complications occurred in 17.8%, while serious complications requiring reoperation occurred in only 3.5%. There was 1 complete flap failure. Primary healing occurred in 84.9% of patients, with 94.5% of patients obtaining a healed perineal wound within 30 days. These results support the use of the transpelvic vertical rectus flap in difficult perineal wound reconstruction.     

Vacuum-assisted abdominal closure: its role in the treatment of complex abdominal and perineal wounds. Experience in 48 patients

INTRODUCTION: Vacuum-assisted closure (VAC) is a promising approach for the management of complex abdominal and perineal wounds. This paper summarizes our experience with this therapeutic modality and demonstrates its efficacity in difficult situations. PATIENTS AND METHODS: From January 2003 until December 2005, 48 patients (age 30-89) were treated with VAC therapy for open abdomen, infected laparotomy wounds, or tissue loss due to debridement of Fournier's gangrene. Wound dressings were changed every 2-3 days. RESULTS: Thirty-eight patients (79%) had major co-morbid conditions liable to impact negatively on wound healing. The treatment duration with VAC varied from 20-30 days with an average of eleven dressing changes (minimum 3-maximum 18). Treatment was effective in all patients. Spontaneous closure was achieved in 36 cases (75%); nine patients (19%) required a split-thickness skin graft, and three (6%) underwent delayed secondary closure. CONCLUSION: In our institution, VAC has become the treatment of choice for complex abdominal and perineal wounds. It is a safe, simple, and effective technique to speed wound healing and it has reduced the duration of hospital treatment in difficult clinical situations and in patients whose general condition is often severely compromised.