Inflammatory inert poly(ethylene glycol)--protein wound dressing improves healing responses in partial- and full-thickness wounds

In this study, a novel soft hydrogel system based on the poly(ethylene glycol)-protein conjugates was evaluated as an occlusive wound dressing material. The hydrogel material, referred by the name of BioAquacare, contains up to 96% of the liquid and is formulated with phosphate-buffered saline and safe preservative to control bacterial load in the open wounds. Performance of the BioAquacare as a wound dressing material was assessed in partial- and full-thickness wounds in pigs. Wound analysis comprised macroscopic determination of the wound size, histological examination of the healing tissues and biochemical characterisation of wound exudates. The wounds treated with BioAquacare healed without any signs of inflammation, skin irritation, oedema or erythema. Cellular composition of the reepithelialised wounds was very similar to that of the normal skin, with a well-developed stratum corneum and epithelial layer. It was observed that BioAquacare plays the role of a liquid compartment, which provides pronounced hydration effect and helps maintain a natural moist environment of the healing tissues. BioAquacare showed relatively low protein-absorbing activity, absorbing predominantly low-molecular-weight molecules, including interleukin (IL)-1beta, IL-6, transforming growth factor-beta1 and products of haemoglobin degradation. It is concluded that application of the moist BioAquacare dressing promotes fast reepithelialisation by creating favourable environment for keratinocytes proliferation and it also reduces scarring. The results show that BioAquacare can be considered as a safe, biocompatible and inflammatory inert wound dressing material.     

A newly developed hydrofibre dressing, in the treatment of partial-thickness burns

A newly developed, carboxymethylcellulose based hydrofibre dressing, Aquacel, was tested for the treatment of partial thickness burns. In this study 84 patients with mainly partial thickness burns were included, 76 patients received 1 or 2 days pre-treatment with a topical antimicrobial agent. Clinical behaviour showed a strong resemblance with cadaver skin treatment with respect to adherence to the wound. Adverse reactions, incidence of clinical wound infection, healing time and the need for wound excision and grafting were analysed, as was the final outcome using the 'Vancouver Scar Scale'. The mean size of the wounds treated with the hydrofibre dressing was 6.0% body surface area (min: 1%, max: 18%). Two patients clinically showed signs of a wound infection during treatment, but in general wound cultures were low or negative. In 42 patients (50%) the wounds healed completely within 10 days, in six patients (7%) small defects remained that healed by further treatment with a topical antimicrobial cream. In 36 patients (43%) excision and grafting of the remaining deeper parts of the wounds was performed as this is the standard therapy in the centre for all burned areas that have not healed within 2-3 weeks post-injury. The extent of the surgical procedures was limited since 66.1% of the wound area had healed already at the end of the hydrofibre treatment. In 54 patients the outcome of the treatment after 2-3 months was analysed by means of the Vancouver Scar Scale, which showed favourable results in general, and especially for patients who did not require surgery. Compared to earlier experience with allograft skin it was concluded that hydrofibre dressing is a safe, suitable and easy to use material for treatment of partial thickness burns.     

Outcomes of conventional wound treatment in a comprehensive wound center

Conventional wound care is the elementary treatment modality for treating chronic wounds. However, early treatment with topical growth factors may be needed for a subset of chronic wounds that fail to heal with good wound care alone. A prospective nonrandomized case series from a single-community outpatient wound care clinic is presented here in an effort to identify the subset of chronic wounds that may require early adjuvant intervention. There were 378 consecutive patients with 774 chronic wounds of varying etiology. All patients received 4 weeks of conventional wound care, including weekly debridement and twice-daily dressing changes. Wounds not reduced by 50 per cent volume at 4 weeks were nonrandomly treated with human skin equivalent (Apligraf), platelet-derived wound healing factor, or platelet-derived growth factor isoform BB (becaplermin gel, Regranex). A total of 601 of 774 (78%) wounds healed regardless of treatment type. The median time to heal for all wounds was 49 days (interquartile range = 26-93). More women than men healed (85% vs 71%, respectively, P < 0.0001). Diabetic wounds were as likely to heal as nondiabetic wounds (78% vs 80%, P = 0.5675). Wounds that did not heal had larger volumes and higher grade compared with wounds that healed (P < 0.0001 for both variables). The data presented here show that the majority of chronic wounds will heal with conventional wound care, regardless of etiology. Large wounds with higher grades are less responsive to conventional wound care and will benefit from topical growth factor treatment early in the treatment course.     

Healing of a deep skin wound using a collagen sponge as dressing in the animal experiment]

The high number of available wound dressing materials as well as the scientific reports about the topic indicates that the problem of an ideal wound dressing is not jet solved. In the last thirty years lot of scientific reports about collagen as wound covering has been published. The positive effect of collagen by his application on a wound ist well known. We investigated the effect of a collagen sponge on healing of full thickness skin wound in guinea pig. The animals were divided in two control groups and two experimental groups. In the control group there were air exposed wounds and another wounds covered with paraffin gauze. In the experimental groups were such wounds covered with natural reconstituted collagen sponge as well as wounds covered with chemically prepared collagen sponge with hexamethyldiisocyanat. The results were compared. The air exposed wounds healed in 50 days, the wounds covered with paraffin gauze healed in 48 days. By covering the wounds with collagen sponge the healing was shortened in 24 or 27 days respectively. Not only the healing time was shortened but also the quality of the wound repair by dressing the wounds with collagen sponge was enhanced.     

Evaluation of a bi-layer wound dressing for burn care. II. In vitro and in vivo bactericidal properties

We have recently designed a medicated bi-layer wound dressing to address the key requirements for treating external, contaminated war wounds. This study assessed the in vitro and in vivo bactericidal efficacies of the DRDC hydrogel/polyurethane wound dressing. Chloramphenicol- and chlorhexidine-loaded DRDC dressings produced significantly larger zones of inhibition against Pseudomonas aeruginosa than the other medicated dressings for 4 d. Chlorhexidine-loaded Allevyn and Hydrasorb remained bactericidal for 48 h only. Chloramphenicol-loaded Hydrasorb and Allevyn remained bactericidal for 1 and 3 d, respectively. Ps. aeruginosa and Staphylococcus epidermidis counts in wounds treated with chlorhexidine- and chloramphenicol-loaded DRDC dressings for 24 h were 1-3-log lower than those of control wounds. While Ps. aeruginosa counts in the wounds on day 4 were comparable following daily changes of either antiseptic-loaded dressings, chlorhexidine showed a 75% greater bactericidal efficacy against Staph. epidermidis than chloramphenicol. Though increasing the frequency of dressing changes led to a greater reduction in the wound bacterial load, the contamination levels of all antiseptic-treated wounds remained below 10(5) CFU/g of wound. Cerium nitrate-loaded dressings did not exert any bactericidal effect, irrespective of the experimental conditions. These data show that the DRDC dressing is effective in delivering medications, such as an antimicrobial agent, to the wound bed.     

Clinical experience with collagenous wound dressing in severe traumatic soft tissue injuries]

We treated 34 patients during 1987-1990 with a collagen wound dressing. Eleven patients had traumatic soft tissue defects, 10 patients had 3 degrees-grade open fractures, 7 patients had infected soft tissue wounds and 6 patients had deep 2 degrees and 3 degrees-degree burns. Our clinical experience confirmed the excellent clinical experimental results of collagen wound dressings. In all cases after 4 until 6 days of treatment good granulation and vascularisation of the wound bed was obtained, so that a skin transplant could be performed, which in all cases healed primarily. Moreover, the wound dressing had a good antibacterial effect and integrated actively in the wound healing process.     

Recent advances in topical wound care

There are a wide variety of dressing techniques and materials available for management of both acute wounds and chronic non-healing wounds. The primary objective in both the cases is to achieve a healed closed wound. However, in a chronic wound the dressing may be required for preparing the wound bed for further operative procedures such as skin grafting. An ideal dressing material should not only accelerate wound healing but also reduce loss of protein, electrolytes and fluid from the wound, and help to minimize pain and infection. The present dictum is to promote the concept of moist wound healing. This is in sharp contrast to the earlier practice of exposure method of wound management wherein the wound was allowed to dry. It can be quite a challenge for any physician to choose an appropriate dressing material when faced with a wound. Since wound care is undergoing a constant change and new products are being introduced into the market frequently, one needs to keep abreast of their effect on wound healing. This article emphasizes on the importance of assessment of the wound bed, the amount of drainage, depth of damage, presence of infection and location of wound. These characteristics will help any clinician decide on which product to use and where,in order to get optimal wound healing. However, there are no ‘magical dressings’. Dressings are one important aspect that promotes wound healing apart from treating the underlying cause and other supportive measures like nutrition and systemic antibiotics need to be given equal attention.KEY WORDS: Moist healing, topical wound care, wet dressings     

Enhanced healing of mitomycin C‐treated healing‐impaired wounds in rats with hydrosheets composed of chitin/chitosan,fucoidan, and alginate as wound dressings

To create a moist environment for rapid wound healing, a hydrosheet composed of alginate, chitin/chitosan, and fucoidan (ACF‐HS) has been developed as a functional wound dressing. The aim of this study was to evaluate the accelerating effect of ACF‐HS on wound healing for rat mitomycin C‐treated healing‐impaired wounds. Full‐thickness skin defects were made on the back of rats and mitomycin C was applied onto the wound for 10 minutes to prepare a healing‐impaired wound. After thoroughly washing out the mitomycin C, ACF‐HS was applied to the healing‐impaired wounds. The rats were later euthanized and histological sections of the wounds were prepared. The histological examinations showed significantly advanced granulation tissue and capillary formations in the healing‐impaired wounds treated with ACF‐HS on days 7 and 14, in comparison with that in alginate fiber (Kaltostat^®), hydrogel wound dressing (DuoACTIVE^®), and nontreatment (negative control). Furthermore, in cell culture studies, ACF‐HS‐absorbed serum and fibroblast growth factor‐2 was found to be proliferative for fibroblasts and endothelial cells, respectively, and ACF‐HS‐absorbed serum was found to be chemoattractive for fibroblasts. However, our results may not be strictly comparable with general healing‐impaired wound models in humans because of the cell damage by mitomycin C. In addition, more biocompatibility studies of fucoidan are essential due to the possibility of renal toxicity.     

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).     

Development of a PHMB hydrogel‐modified wound scaffold dressing with antibacterial activity

Current wound scaffold dressing constructs can facilitate wound healing but do not exhibit antibacterial activity, resulting in high infection rates. We aimed to endow wound scaffold dressing with anti‐infective ability by polyhexamethylenebiguanide (PHMB). We prepared PHMB hydrogel at varying concentrations (0.25%, 0.5%, 1%, 2%) and assessed release and cytotoxicity. PHMB hydrogel was added to the wound scaffold dressing to generate a PHMB hydrogel‐modified wound scaffold dressing. Wound healing and infection prevention were evaluated using a full‐thickness skin defect model in rats. In vitro, the hydrogel PHMB release time positively correlated with PHMB concentration, with 1% allowing sufficiently long release time to encompass the high‐incidence period (3‐5 days) of infection following wound scaffold dressing implantation. Implantation of 1% PHMB hydrogel into the skin did not cause adverse responses. in vitro cytotoxicity assays showed the PHMB hydrogel‐modified wound scaffold dressing did not significantly affect proliferation of fibroblasts or vascular endothelial cells, 99.90% vs 99.84% for fibroblasts and 100.21% vs 99.28% for vascular endothelial cells at 21 days. Transplantation of PHMB hydrogel‐modified wound scaffold dressing/unmodified wound scaffold dressing on the non‐infected wounds of rats yielded no significant difference in relative vascularization rate, 47.40 vs 50.87 per view at 21 days, whereas bacterial content of the wound tissue in the PHMB hydrogel‐modified wound scaffold dressing group was significantly lower than the unmodified wound scaffold dressing group, (1.80 ± 0.35) × 10³ vs (9.34 ± 0.45) × 10³ at 14 days. Prevalence of persistent wound infection in the rats receiving PHMB hydrogel‐modified wound scaffold dressing transplantation onto infected wounds was significantly lower than the unmodified wound scaffold dressing group, 30% vs 100%. PHMB hydrogel‐modified wound scaffold dressing exhibited suitable antibacterial ability, and its biological activity did not significantly differ from that of the unmodified wound scaffold dressing, thereby allowing it to effectively prevent infection following wound scaffold dressing implantation.     

Exploiting potency of negative pressure in wound dressing using limited access dressing and suction-assisted dressing

Role of negative pressure dressing and moist wound healing are well established in the treatment of both acute and chronic wounds with certain advantages and disadvantages in both the techniques. Both these techniques prevents wound colonization, but the negative pressure dressing method has proved to have a greater potency to remove secretions, prevent wound invasion and eradication established infection. In both these techniques there is no accessibility to wound environment. Limited access dressing (LAD) is a moist wound dressing with negative pressure. It provides limited access to the wound through two small ports for both dressers and pathogens. The LAD design has notable advantages like wound isolation that reduces chance of wound colonization and safe disposal of infected materials (important factor to reduce hospital-acquired infections), while avoiding some major disadvantages such as opacity of dressing materials, inaccessible offensive smelling wound environment, and relatively high treatment costs. In LAD a definite intermittent negative pressure regimen is followed. The intermittent negative pressure (cycle of 30 minutes suction and 3½ hours rest) is effective. Overall, the LAD is a safe and effective alternative to conventional dressing methods. LAD is an excellent research tool for wound healing as frequent/continuous record of wound healing is possible without disturbing the wound healing process. LAD is an effective dressing for limb salvage in cases of acute and chronic complex wounds. Leech effect prevents wound related systematic response syndrome and sepsis. Suction-assisted dressing (SAD) is a combination of semiocclusive dressing with negative pressure. It works by removal of fluids by intermittent (like LAD) negative pressure and preventing bacterial invasion. SAD is especially advantageous where soakage is less, there is no dead tissue covering the wound (e.g., following skin grafting), superficial skin wounds (e.g., donor area) and also where LAD is technically difficult to apply over circumferential trunk and neck dressings under anesthesia.KEY WORDS: Limited access dressing, negative pressure wound therapy, suction-assisted dressing     

A Comparative Study of the Burn Wound Healing Properties of Saline-Soaked Dressing and Silver Sulfadiazine in Rats

The purpose of this study was to further investigate that phenomenon and to explore the effect silver sulfadiazine on wound healing. Full-thickness burn wounds were created on the dorsum of Wistar albino rats under anesthesia. The wounds were treated with silver sulfadiazine and saline-soaked dressing for fourteen days, and then observed until healed. Wound surface area was measured each three days. Time to 50% and 90% healing was compared. No clinical infections occurred. Wound half-life and healing times were shortest in the saline-soaked group (P < 0.0001) in full-thickness burns. Wound contraction was delayed by silver sulfadiazine. These data suggest that silver sulfadiazine retard burn wound healing. Infection control without delay of burn wound healing is most appealing and clinical trials are planned.     

The importance of periwound skin in the treatment of "difficult wound"

A "difficult wound" consists of a loosing of cutaneous substance, with multi factor pathogenesis, that doesn't heal spontaneously. The treatment of this pathology is quite complex and first of all requires the analysis of the aetiopathogenesis of the wound, as it can healed only operating on its causes. Cutaneous wounds are formed by three different parts: bottom, border-edge and periwound skin, that must be analysed before every dressing, without overlooking all their components. Periwound skin is the part of skin that stretches for 10 centimetres beyond the wound edge. Our work aims to describe the importance of periwound skin in wound healing process, analysing clinical variants and specific treatment. Studying periwound skin we can provide many information in order to understand the cause of the lesion, to foresee healing time and to chance and find the most proper dressing, optimizing resources consumption.     

Polyurethane film (Opsite) vs. impregnated gauze (Jelonet) in the treatment of outpatient burns: a prospective, randomized study

As it has been shown that re-epithelialization of partial skin thickness wounds can be accelerated if the wound is kept moist, a prospective, randomized clinical study compared the water vapour-semipermeable polyurethane film, Opsite, with the conventional impregnated gauze dressing, Jelonet, in the treatment of outpatient partial skin thickness burns. Fifty-five patients were included: 30 were treated with the polyurethane film and 25 with the conventional dressing. The patients were followed at regular intervals until healing had occurred and were seen 3 months later for evaluation of residual scars and pigmentation. The burns treated with polyurethane films healed with a median of 10 days, while the conventionally treated burns healed with a median of 7 days (P greater than 0.05). Residual scars were noted in 21 per cent of the patients treated with polyurethane films and in 8 per cent treated conventionally (P greater than 0.05). Prophylactic methods should be publicly stressed since one-quarter of the patients were children of 3 years or less who were scalded by split hot liquids. Furthermore the patients' wounds were only briefly cooled before attending medical care. With small burns we advise that cooling should be prolonged until the pain fades then professional assistance should be sought.     

Development of a new wound dressing with antimicrobial delivery capability

A bilaminar wound dressing composed of an outer membrane and an inner three-dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial-impregnated polyurethane membrane. In this study, a gentamycin sulfate-impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full-thickness and split-thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open-label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.     

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.     

Defining complete wound closure: Closing the gap in clinical trials and practice

We investigate how wound closure is determined in recent randomized controlled wound trials and real‐world studies, identify solutions to the current limitations of wound assessment, and propose a standard methodology to define and assess wound healing in research. We searched PubMed for randomized clinical trials using the terms “complete wound closure” and “wound healing rate” and for real‐world studies using the terms “real‐world wound healing,” “real‐world wound data,” and “wound registries” dating from March 2010 through March 2018. We selected studies that had “complete wound closure” or “healed wound” as an endpoint. Sixty‐five trial articles and 10 real‐world articles met our criteria, from which we extracted the wound type studied, definition of healed wound used, wound assessment method, the number of weeks assessed, the number of wounds, and the percent of healed wounds in the study group(s) and control group. There were 7,194 trial wounds included. The most common definition of healing used by 26 studies (40.6%) was complete/full/100% (re)epithelialization or closure without discharge, drainage/scab, and/or dressing. Fifty‐two studies (81.2%) used blinded wound assessment, and at least 10 studies (15.6%) used blinded adjudication. The real‐world studies analyzed more than 901,396 wounds. Only three studies (33.3%) defined a healed/closed wound, two of which used “complete epithelialization.” Eight studies (88.9%) did not define the wound assessment method; none indicated a blinded assessment. We support the Food and Drug Administration definition: 100% reepithelialization of the wound surface with no discernable exudate and without drainage or dressing, confirmed at two visits 2 weeks apart, and we recommend blinded adjudication for wound assessment. The widespread adoption of a standard wound healing definition and assessment method in wound care research would allow for stronger comparisons of treatment effects across studies to improve the evidence base and strengthen the treatment decision‐making process in clinical practice.     

The effects of calcium alginate on wound healing

A non-woven alginate dressing has been used on experimental, full and partial thickness wound models for periods up to 14 days, to assess its effects on wound healing. Histological evaluation has shown that it is an effective haemostat, generally well tolerated by body tissues. Good epidermal healing was seen on all wounds although cellular reactions could be provoked in full thickness wounds without occlusion, if there was an insufficient volume of wound exudate to completely wet the alginate fibres.     

The concurrent use of probiotic microorganism and collagen hydrogel/scaffold enhances burn wound healing: An in vivo evaluation

Treatment of burn wounds is technically demanding and several attempts have been taken to improve wound healing. Silver sulfadiazine antibiotic has been shown to have some beneficial effects on wound healing via reduction in infection. This study was designed to investigate the impact of collagen hydrogel-scaffold dressing with or without topical use of Saccharomyces cerevisiae on cutaneous burn wound healing in rat. Four circular 1 cm cutaneous wounds were created in the dorsum back of rats, 48 h post-burning. Thirty male rats were divided into the three major groups (1–3, n = 10), then the wounds in each group were equally divided into two subgroup treatments (6 treatments), (1) including (a) silver sulfadiazine (SSD) as positive control (PC) and (b) untreated wounds as negative control (NC) (2) including (c) S. cerevisiae and (S.C.) and (d) collagen scaffold (CS), (3) including (e) collagen hydrogel-scaffold (CH-S) and (f) S. cerevisiae with collagen hydrogel-scaffold (CH-S-S). In each group, the animals were euthanized at 12 and 22 days post-injury (DPI) and the skin samples were used for histopathological and biomechanical investigations. Collagen scaffold and hydrogel modulated the inflammation, especially when combined together. Moreover, they increased wound healing, epithelialization and biomechanical performance of wound area and also reduced the scar size. The best results gained when the combination of collagen scaffold and hydrogel were mixed with probiotic. The CH-S biological dressing along with probiotic microorganism (S.C.) significantly increased collagen content compared to the negative controls. Moreover, the CH-S-S treated lesions demonstrated greater ultimate load and stiffness compared to the untreated wounds. In conclusion, application of S. cerevisiae with a bi-phase biological dressing (CH-S) improved the morphological and biomechanical characteristics of the healing burned wounds in rats and the results were comparable to the positive control.     

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.