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1.  The real expansion rate of meshers and micrografts: things we should keep in mind 
Summary
Skin graft expansion techniques (mesh and micrograft) are widely used, but there is ample evidence that skin graft meshers do not provide their claimed expansion rates. Although this finding might not be new for the majority of surgeons, less is known about surgeons’ actual knowledge of expansion rates. The aim of this study was to evaluate the true expansion rates of commonly used expansion techniques with regard to claimed, achieved, and polled results. In the first part of the study, 54 surgeons were polled during an annual burns meeting regarding the most commonly used expansion techniques and expansion ratios; in the second step the true (achievable) expansion rates of the most widely used meshers and micrografts were analysed; and in third step, a poll involving 40 surgeons was conducted to estimate the true expansion rates of the most frequently used skin expansion techniques. The skin meshers (1:1.5 / 1:3) did not achieve their claimed values: (1:1.5) 84.7% of the claimed expansion (mean ± SD: 1:1.27 ± 0.15) and (1:3) 53.1% of the 1:3 (1:1.59 ± 0.15) mesher. The use of the micrografting technique resulted in 99.8% of the 1:3 (1:2.99 ± 0.09), 93.6% of the 1:4 (1:3.74 ± 0.12) and 93.8% of the 1:6 (1:5.63 ± 0.12) claimed expansion rates, respectively. In general the surgeons overestimated the achievable expansion rates. In general the achieved expansion rate was lower than the estimated and claimed expansion rates. The micrografting technique provided reliable and valid expansion rates compared to the skin meshers. We recommend using the micrograft technique when large expansion ratios are required, for example in severe extensive burns.
PMCID: PMC3741003  PMID: 23966895
skin transplantation; skin graft; mesh; micrografting; Meek’s technique
2.  Negative Pressure Wound Therapy 
Executive Summary
Objective
This review was conducted to assess the effectiveness of negative pressure wound therapy.
Clinical Need: Target Population and Condition
Many wounds are difficult to heal, despite medical and nursing care. They may result from complications of an underlying disease, like diabetes; or from surgery, constant pressure, trauma, or burns. Chronic wounds are more often found in elderly people and in those with immunologic or chronic diseases. Chronic wounds may lead to impaired quality of life and functioning, to amputation, or even to death.
The prevalence of chronic ulcers is difficult to ascertain. It varies by condition and complications due to the condition that caused the ulcer. There are, however, some data on condition-specific prevalence rates; for example, of patients with diabetes, 15% are thought to have foot ulcers at some time during their lives. The approximate community care cost of treating leg ulcers in Canada, without reference to cause, has been estimated at upward of $100 million per year.
Surgically created wounds can also become chronic, especially if they become infected. For example, the reported incidence of sternal wound infections after median sternotomy is 1% to 5%. Abdominal surgery also creates large open wounds. Because it is sometimes necessary to leave these wounds open and allow them to heal on their own (secondary intention), some may become infected and be difficult to heal.
Yet, little is known about the wound healing process, and this makes treating wounds challenging. Many types of interventions are used to treat wounds.
Current best practice for the treatment of ulcers and other chronic wounds includes debridement (the removal of dead or contaminated tissue), which can be surgical, mechanical, or chemical; bacterial balance; and moisture balance. Treating the cause, ensuring good nutrition, and preventing primary infection also help wounds to heal. Saline or wet-to-moist dressings are reported as traditional or conventional therapy in the literature, although they typically are not the first line of treatment in Ontario. Modern moist interactive dressings are foams, calcium alginates, hydrogels, hydrocolloids, and films. Topical antibacterial agents—antiseptics, topical antibiotics, and newer antimicrobial dressings—are used to treat infection.
The Technology Being Reviewed
Negative pressure wound therapy is not a new concept in wound therapy. It is also called subatmospheric pressure therapy, vacuum sealing, vacuum pack therapy, and sealing aspirative therapy.
The aim of the procedure is to use negative pressure to create suction, which drains the wound of exudate (i.e., fluid, cells, and cellular waste that has escaped from blood vessels and seeped into tissue) and influences the shape and growth of the surface tissues in a way that helps healing. During the procedure, a piece of foam is placed over the wound, and a drain tube is placed over the foam. A large piece of transparent tape is placed over the whole area, including the healthy tissue, to secure the foam and drain the wound. The tube is connected to a vacuum source, and fluid is drawn from the wound through the foam into a disposable canister. Thus, the entire wound area is subjected to negative pressure. The device can be programmed to provide varying degrees of pressure either continuously or intermittently. It has an alarm to alert the provider or patient if the pressure seal breaks or the canister is full.
Negative pressure wound therapy may be used for patients with chronic and acute wounds; subacute wounds (dehisced incisions); chronic, diabetic wounds or pressure ulcers; meshed grafts (before and after); or flaps. It should not be used for patients with fistulae to organs/body cavities, necrotic tissue that has not been debrided, untreated osteomyelitis, wound malignancy, wounds that require hemostasis, or for patients who are taking anticoagulants.
Review Strategy
The inclusion criteria were as follows:
Randomized controlled trial (RCT) with a sample size of 20 or more
Human study
Published in English
Summary of Findings
Seven international health technology assessments on NPWT were identified. Included in this list of health technology assessments is the original health technology review on NPWT by the Medical Advisory Secretariat from 2004. The Medical Advisory Secretariat found that the health technology assessments consistently reported that NPWT may be useful for healing various types of wounds, but that its effectiveness could not be empirically quantified because the studies were poorly done, the patient populations and outcome measures could not be compared, and the sample sizes were small.
Six RCTs were identified that compared NPWT to standard care. Five of the 6 studies were of low or very low quality according to Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. The low and very low quality RCTs were flawed owing to small sample sizes, inconsistent reporting of results, and patients lost to follow-up. The highest quality study, which forms the basis of this health technology policy assessment, found that:
There was not a statistically significant difference (≥ 20%) between NPWT and standard care in the rate of complete wound closure in patients who had complete wound closure but did not undergo surgical wound closure (P = .15).
The authors of this study did not report the length of time to complete wound closure between NPWT and standard care in patients who had complete wound closure but who did not undergo surgical wound closure
There was no statistically significant difference (≥ 20%) in the rate of secondary amputations between the patients that received NPWT and those that had standard care (P = .06)
There may be an increased risk of wound infection in patients that receive NPWT compared with those that receive standard care.
Conclusion
Based on the evidence to date, the clinical effectiveness of NPWT to heal wounds is unclear. Furthermore, saline dressings are not standard practice in Ontario, thereby rendering the literature base irrelevant in an Ontario context. Nonetheless, despite the lack of methodologically sound studies, NPWT has diffused across Ontario.
Discussions with Ontario clinical experts have highlighted some deficiencies in the current approach to wound management, especially in the community. Because NPWT is readily available, easy to administer, and may save costs, compared with multiple daily conventional dressing changes, it may be used inappropriately. The discussion group highlighted the need to put in place a coordinated, multidisciplinary strategy for wound care in Ontario to ensure the best, continuous care of patients.
PMCID: PMC3379164  PMID: 23074484
3.  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.
doi:10.4103/0970-0358.101321
PMCID: PMC3495389  PMID: 23162238
Moist healing; topical wound care; wet dressings
4.  Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. 
In man and domestic animals, scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in adverse aesthetics, loss of function, restriction of tissue movement and/or growth and adverse psychological effects. Current treatments are empirical, unreliable and unpredictable: there are no prescription drugs for the prevention or treatment of dermal scarring. Skin wounds on early mammalian embryos heal perfectly with no scars whereas wounds to adult mammals scar. We investigated the cellular and molecular differences between scar-free healing in embryonic wounds and scar-forming healing in adult wounds. Important differences include the inflammatory response, which in embryonic wounds consists of lower numbers of less differentiated inflammatory cells. This, together with high levels of morphogenetic molecules involved in skin growth and morphogenesis, means that the growth factor profile in a healing embryonic wound is very different from that in an adult wound. Thus, embryonic wounds that heal without a scar have low levels of TGFbeta1 and TGFbeta2, low levels of platelet-derived growth factor and high levels of TGFbeta3. We have experimentally manipulated healing adult wounds in mice, rats and pigs to mimic the scar-free embryonic profile, e.g. neutralizing PDGF, neutralizing TGFbeta1 and TGFbeta2 or adding exogenous TGFbeta3. These experiments result in scar-free wound healing in the adult. Such experiments have allowed the identification of therapeutic targets to which we have developed novel pharmaceutical molecules, which markedly improve or completely prevent scarring during adult wound healing in experimental animals. Some of these new drugs have successfully completed safety and other studies, such that they have entered human clinical trials with approval from the appropriate regulatory authorities. Initial trials involve application of the drug or placebo in a double-blind randomized design, to experimental incision or punch biopsy wounds under the arms of human volunteers. Based on encouraging results from such human volunteer studies, the lead drugs have now entered human patient-based trials e.g. in skin graft donor sites. We consider the evolutionary context of wound healing, scarring and regeneration. We hypothesize that evolutionary pressures have been exerted on intermediate sized, widespread, dirty wounds with considerable tissue damage e.g. bites, bruises and contusions. Modem wounds (e.g. resulting from trauma or surgery) caused by sharp objects and healing in a clean or sterile environment with close tissue apposition are new occurrences, not previously encountered in nature and to which the evolutionary selected wound healing responses are somewhat inappropriate. We also demonstrate that both repair with scarring and regeneration can occur within the same animal, including man, and indeed within the same tissue, thereby suggesting that they share similar mechanisms and regulators. Consequently, by subtly altering the ratio of growth factors present during adult wound healing, we can induce adult wounds to heal perfectly with no scars, with accelerated healing and with no adverse effects, e.g. on wound strength or wound infection rates. This means that scarring may no longer be an inevitable consequence of modem injury or surgery and that a completely new pharmaceutical approach to the prevention of human scarring is now possible. Scarring after injury occurs in many tissues in addition to the skin. Thus scar-improving drugs could have widespread benefits and prevent complications in several tissues, e.g. prevention of blindness after scarring due to eye injury, facilitation of neuronal reconnections in the central and peripheral nervous system by the elimination of glial scarring, restitution of normal gut and reproductive function by preventing strictures and adhesions after injury to the gastrointestinal or reproductive systems, and restoration of locomotor function by preventing scarring in tendons and ligaments.
doi:10.1098/rstb.2004.1475
PMCID: PMC1693363  PMID: 15293811
5.  Reconstructive Hair Transplantation of the Face and Scalp 
Seminars in Plastic Surgery  2005;19(2):159-166.
ABSTRACT
Quantum leap advancements in hair transplantation have occurred in the past 10 to 15 years, particularly the use of micrografts (one- to two-hair follicular unit grafts) and minigrafts (three- to four-hair follicular unit grafts) used in large numbers (> 1000 grafts) in a single session (megasession). This was initially described for the treatment of male pattern baldness. Since that time I have found many other applications, particularly in facial and scalp reconstruction. Common causes for aesthetic reconstructive hair restoration in my experience include: hair loss due to facelift and forehead lift procedures, revision of unsatisfactory results from previous hair transplantation, burn alopecia, congenital reasons, postoncological resections, and idiopathic. The basic technique is described in detail, including the variations for each of the challenging anatomic areas including sideburns and temporal hairline, eyebrows, eyelashes, mustache, beard, and remaining scalp. Especial attention is given to the direction of hair growth, texture, aesthetic planning, and absence of detectable scars, so as to mimic nature. The use of micrografts and minigrafts in the aesthetic reconstruction of the face and scalp has been found to be safe and predictable and has provided a high level of patient satisfaction.
doi:10.1055/s-2005-871732
PMCID: PMC2884705
Reconstructive; hair transplantation; micrografting; minigrafting
6.  The Use of Split-Thickness Skin Grafts on Diabetic Foot Ulcerations: A Literature Review 
Plastic Surgery International  2012;2012:715273.
Diabetic foot ulcerations are historically difficult to treat despite advanced therapeutic modalities. There are numerous modalities described in the literature ranging from noninvasive topical wound care to more invasive surgical procedures such as primary closure, skin flaps, and skin grafting. While skin grafting provides faster time to closure with a single treatment compared to traditional topical wound treatments, the potential risks of donor site morbidity and poor wound healing unique to the diabetic state have been cited as a contraindication to its widespread use. In order to garner clarity on this issue, a literature review was undertaken on the use of split-thickness skin grafts on diabetic foot ulcers. Search of electronic databases yielded four studies that reported split-thickness skin grafts as definitive means of closure. In addition, several other studies employed split-thickness skin grafts as an adjunct to a treatment that was only partially successful or used to fill in the donor site of another plastic surgery technique. When used as the primary closure on optimized diabetic foot ulcerations, split-thickness skin grafts are 78% successful at closing 90% of the wound by eight weeks.
doi:10.1155/2012/715273
PMCID: PMC3361270  PMID: 22666573
7.  Glycerin-Based Hydrogel for Infection Control 
Advances in Wound Care  2012;1(1):48-51.
Problem
Infection is a major problem in the health and wellbeing of patients in hospitals, nursing homes, and other medical facilities as well as the homecare patients and the general public. According to Scientia Advisors, wound care costs the healthcare system over $7 billion in 2009. After adding the cost associated with potential complications such as infections, extended physician care, and lengthy hospital stays, the annual wound care expenditures well exceeded over $20 billion.1 There are 20 million reported cases of diabetes per year and more every day. Because of the fact that leg ulcers are the number one health problem of men coupled with the rise in drug resistance of infections, the importance of providing the professional and the public with relatively simple and affordable wound care is of extreme importance. Often the wounds can become chronic wounds, which then result in long-term nursing expense in time and supplies or, worse yet, can result in expensive amputations ranging from $5000 to $40,000 per patient.
Solution
There are many dressing options now available for treating wounds with components such as glycerin, honey, salt, and many other natural products, with some dressings being more appropriate than others. In 1988, a patented glycerin-based dressing was introduced to the market, called Elasto-Gel™.2
New Technology
Elasto-Gel™ is a glycerin-based gel sheet (65%) combined with a hydrophilic polymer that causes the sheet to absorb the exudate from the wound and simultaneously release the glycerin from the gel, which adds many benefits to the wound for excellent healing outcomes. The gel sheet is 1/8th of an inch thick with a four-way stretch backing. It has the ability to absorb 3–4 times its own weight of fluids. The dressing will not dry out or allow the exudate to dry out, thus keeping the dressing from becoming bonded to the wound or the surrounding tissue. It does not have adhesive properties and, therefore, will not cause damage to the wound bed or periwound area upon dressing removal. Because of the thickness, the product provides excellent cushion and padding support. It has been also proven to be bacteriostatic/fungistatic. (Bacteriostatic is the ability to restrain the development or reproduction of bacteria.3)
Product Technology
Glycerin is a huamectant by definition and has been recognized by the U.S. Food and Drug Administration (FDA). Humectants attract, bind, and hold moisture to the site of application. The actual concentration of glycerin in a wound dressing is indicative of the ability to absorb excess moisture. Exudate management is an important function of topical treatment. The ability to absorb drainage and prevent pooling of exudate in the wound or on the surrounding skin are attributes specific to high glycerin content. Perhaps, the most significant advantage of the glycerin-based hydrogel sheet is its impact on wound bioburden and pathogenic organisms.4 Glycerin is a simple three-carbon tri-alcohol and is a natural humectant. It is used as a carrier in many medicines and as plasticizer in gelatin gel capsules. Glycerin is a component of cosmetics, conditioners, soaps, foods, and other common products. It is a component of mono-, di-, and triglycerides naturally occurring in the body. These glycerides and glycerin are constantly reacted with each other by the natural enzymes and reversed with the natural metabolic processes already present in the body. Any glycerin that may be absorbed into the body fluid is rapidly diluted in these fluids and is no longer toxic but is metabolized as another component of the food chain. It is well known that glycerin in high concentration will exhibit dehydrating effect on many systems including living cells by the commonly known process of osmosis. (Osmosis: the flow or diffusion that takes place through a semipermable membrane, as of living cell, typically separating a solvent such as water, thus bringing about equilibrium conditions.5) It has been shown that glycerin at high concentration will be cytotoxic to all cells that have been tested if they are exposed long enough. These properties of glycerin have been recognized by the European Skin Bank, where they use 85% glycerin solutions to store cadaver skin at ∼42F, and can be used for potential wound coverings. The cadaver skin that has been prepared by this method has been available since 1994.6 The concern for safety resulted in a three-day international synmposium7 with emphasis on glycerin-preserved cadaver skin providing healthy environment for the preserved skin to be successfully accepted without rejection, having no complications of infection and providing excellent healing outcomes and minimal scaring. Additional research by Dr. David P. Mackie of the Red Cross Hospital, The Netherlands, reported that using 85% glycerin solutions had slow bactericidal effects and also showed virocidal activity on several types of viruses.8 Dr. Hoekstra has observed that within 2 hours after application of Elasto-Gel™, the inflammatory reaction is reduced.9 Vandeputte, Belgium, showed that wounds covered with Elasto-Gel™ had fewer myofibroblasts than those covered with hydrocolloid.10 It has been proposed that myofibroblasts in high concentrations contribute to the formation of hypertrophic and keloid scars. As noted earlier, there is less scar formation when glycerin-based gel sheets are used. The data sited here have shown that glycerin and glycerin-based products are effective antimicrobial agents with less side effects. Many verbal reports along with personal communications have indicated that applying glycerin-based gel sheets to stalled wounds, some 15–20-year-old chronic wounds, resulted in healing in 1–20 weeks (data/case studies on file).
Indications for Use
Elasto-Gel™ has been approved for all types of wounds, that is, pressure ulcers, acute and chronic wounds, diabetic wounds, traumatic wounds, dermatology wounds, cancer tumors, and first- and second-degree burns, to name a few. Because of the product's features and benefits, it may be used on a variety of wounds. Because of its padding properties, it may be also used as a preventative product over bony prominence areas so that wounds do not occur. The glycerin properties act as a skin substitute and may also be used for scar reduction.
Caution
Elasto-Gel™ is not approved for third-degree burns as no dressing has been approved by the FDA for this type of wound.
doi:10.1089/wound.2011.0288
PMCID: PMC3839013  PMID: 24527279
8.  Clinical Impact Upon Wound Healing and Inflammation in Moist, Wet, and Dry Environments 
Advances in Wound Care  2013;2(7):348-356.
Significance
Successful treatment of wounds relies on precise control and continuous monitoring of the wound-healing process. Wet or moist treatment of wounds has been shown to promote re-epithelialization and result in reduced scar formation, as compared to treatment in a dry environment.
Recent Advances
By treating wounds in a controlled wet environment, delivery of antimicrobials, analgesics, other bioactive molecules such as growth factors, as well as cells and micrografts, is allowed. The addition of growth factors or transplantation of cells yields the possibility of creating a regenerative wound microenvironment that favors healing, as opposed to excessive scar formation.
Critical Issues
Although several manufacturers have conceived products implementing the concept of moist wound healing, there remains a lack of commercial translation of wet wound-healing principles into clinically available products. This can only be mitigated by further research on the topic.
Future Directions
The strong evidence pointing to the favorable healing of wounds in a wet or moist environment compared to dry treatment will extend the clinical indications for this treatment. Further advances are required to elucidate by which means this microenvironment can be optimized to improve the healing outcome.
doi:10.1089/wound.2012.0412
PMCID: PMC3842869  PMID: 24587972
9.  A porcine model of full-thickness burn, excision and skin autografting 
Acute burn wounds often require early excision and adequate coverage to prevent further hypothermia, protein and fluid losses, and the risk of infection. Meshed autologous skin grafts are generally regarded as the standard treatment for extensive full-thickness burns. Graft take and rate of wound healing, however, depend on several endogenous factors. This paper describes a standardized reproducible porcine model of burn and skin grafting which can be used to study the effects of topical treatments on graft take and re-epithelialization.
Procedures provide a protocol for successful porcine burn wound experiments with special focus on pre-operative care, anesthesia, burn allocation, excision and grafting, postoperative treatment, dressing application, and specimen collection. Selected outcome measurements include percent area of wound closure by planimetry, wound assessment using a clinical assessment scale, and histological scoring.
The use of this standardized model provides burn researchers with a valuable tool for the comparison of different topical drug treatments and dressing materials in a setting that closely mimics clinical reality.
doi:10.1016/j.burns.2008.03.013
PMCID: PMC2637517  PMID: 18617332
Burn; Burn excision; Wound healing; Reconstruction; Autograft
10.  Which dressing do donor site wounds need?: study protocol for a randomized controlled trial 
Trials  2011;12:229.
Background
Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds.
Methods
A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale). Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009.
Discussion
This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s) that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such patients. Thus, we aim to contribute a well-designed trial, relevant to all clinicians involved in the care for donor site wounds, which will help enhance uniformity and quality of care for these patients.
Trial registration
http://www.trialregister.nl, NTR1849. Date registered: June 9, 2009
doi:10.1186/1745-6215-12-229
PMCID: PMC3219559  PMID: 21999705
11.  CICATRIZATION OF WOUNDS  
In the study of the action of non-antiseptic substances on the rate of cicatrization, the chief obstacle encountered is the facility with which wounds become reinfected under an aseptic dressing. At the beginning of Experiment 1 the wound was sterile. It was subjected to flushing with distilled water for 2 hours, then to flushing with 30 per cent sodium chloride solution for another 2 hours. During that time no special precaution was taken to sterilize the wound and the dressing was left intact until the following morning. It was then found that the wound contained from 30 to 50 bacteria per field. The following day, after the wound had been subjected to the same treatment, the number of bacteria had increased to 50 and 100 per field, and as an immediate consequence the surface of the wound increased from 12 to 12.6 sq. cm. in 2 days. The wound was then dressed antiseptically and was found to be sterile 3 days later. Reinfection again took place the following day in spite of antiseptic dressing with chloramine paste 4 parts per 1,000, which was applied for 20 hours. In Experiment 2 similar results were observed. After 2 days of flushing with distilled water, the number of bacteria had increased to 50 per field. The wound was thereupon sterilized, but new reinfection ensued a few days later. Another wound on the same patient became reinfected under the same conditions after 1 day of sterile dressing. In none of the patients could the wounds be kept in a sterile condition throughout the whole experiment. It was impossible to maintain the sterility of a wound under aseptic dressing. Dakin's solution was therefore injected every 4 hours, or less often, according to the degree of infection, or chloramine paste was applied during the night. If there were 3 or 4 bacteria per field, the experiment was discontinued in order that the wound might be sterilized again. The cicatrization and bacteriological curves of Experiment 4 show that by the application of chloramine paste a wound may be maintained in an appropriately bacteriological condition for carrying out an experiment. Nevertheless, in spite of the antiseptic precautions taken, it was necessary to interrupt this experiment on two occasions, on December 13 to 15 and on December 18 to 22, in order that a complete sterilization of the wound might be effected. When the sterilization was performed as soon as the bacteria were discovered, little retardation occurred in the process of cicatrization. Moreover, the reinfection from the skin was often due to fine bacilli which have but mild retarding action on the rate of healing. The use of at least six flushings in 2 hours with Dakin's solution or of 12 hours' dressing with chloramine paste 10 parts per 1,000, was necessary to keep the wound in a condition of surgical asepsis. The action of distilled water was studied in Experiments 1, 2, and 3. In Experiment 1 the wound was subjected to flushing with distilled water first for 2 hours, then 4 hours, and later for 8 hours per day. The wound was maintained in a condition of mild infection. No marked modification, either acceleration or retardation, was noted in the rate of repair during the period that the treatment was applied. From November 21 to 25 the wound was almost clean and the observed curve remained parallel to the calculated curve, showing that distilled water did not retard the rate of healing. In Experiment 2 the wound was subjected to uninterrupted flushing with distilled water, first for 2 and 8 hours, then for 24 hours. It was continued from November 24 to 30; viz., for 112 hours out of 120, without the occurrence of any marked modification of the course of healing. The bacteriological curve showed that from November 22 to 27 inclusive the wound was kept aseptic. The slight retardation which occurred afterwards was probably brought about by the infection. In Experiment 3 the wound was subjected to flushing with distilled water, first for 2, then for 4, 6, and 8 hours, a total of 20 hours in 4 days. From November 21 to 24 the wound remained surgically aseptic. No modification in the rate of healing occurred. The action of the hypertonic sodium chloride solution was studied in a similar way. In Experiment 4 the wound was flushed at first with 40 per cent sodium chloride solution, from December 4 to 9 for 12 hours a day, and from December 10 to 13 for 24 hours a day, making a total of 144 hours out of 240 hours. At the end of this time the surface area of the wound coincided exactly with the calculated area. Owing to reinfection the experiment was suspended. From December 24 to 29 the wound was kept in contact with 50 per cent sodium chloride solution for 54 hours, and after December 30 flushing with 80 per cent solution for 24 hours a day was resorted to. The total amount of time involved in the above treatments was 174 hours with 40 per cent solution, 72 hours with 50 per cent solution, and 120 hours with 80 per cent solution. On January 1, the surface measured 11 sq. cm. and the calculated surface was 11.3 sq. cm. On January 5 the. surface observed was 10 sq. cm. and the calculated surface was 9 sq. cm. It should be noticed that on January 5 the bacteria numbered 4 per field, which might account for the difference. In Experiment 5 the wound was flushed for 24 hours every day with 50 per cent sodium chloride solution from December 11 to 18, a total of 192 hours. From December 18 to 24 the wound was dressed with agar-agar cakes containing 40 per cent sodium chloride. The concentration was raised to 50 per cent from December 24 to 27. The cicatrization curve indicates only a slight retardation of the repair which can be attributed to infection when both cicatrization and infection curves are compared. The temporary acceleration on the 13th may have been due to the influence of the dressing, but as it did not occur again an experimental error is probably the cause of the change observed in the curve. In Experiment 6 two practically identical wounds at a distance of but a few centimeters from each other were located on the right thigh of Patient 721. The areas of the wounds were respectively 40 and 33 sq. cm. One of the wounds was flushed with distilled water only. The other was subjected to the action of 40 per cent sodium chloride solution. From December 20 to 25 both wounds were in a condition of surgical asepsis. However, the cicatrization curves show that in spite of the difference of treatment the rate of healing was not modified. The rate of healing of the wounds did not therefore apparently undergo any measurable modification under the influence of distilled water or hypertonic salt solution. It is well known that the osmotic changes of the medium have a marked influence on tissues deprived of circulation. But it seems that a tissue with normal circulation is protected by it against the changes of the osmotic pressure occurring at its surface. The above experiments show that apparently the conditions of the tissues of a wound are not modified by the changes of the osmotic pressure of the dressing. The beneficial effects of hypertonic sodium chloride solution on the sterilization of wounds and on the rate of healing recently described by various surgeons are possibly an illusion due to lack of precise technique.
PMCID: PMC2125649  PMID: 19868150
12.  Meshed skin grafts placed upside down can “take” if desiccation is prevented 
Plastic and reconstructive surgery  2010;125(3):855-865.
Background
The role of the wet environment in wound healing has been investigated in various studies. The current study explores the role of the wet wound environment in promoting healing of skin grafts. We hypothesized that survival of the skin grafts is not only dependent on the orientation of transplantation, but also on the environment into which the skin is transplanted.
Methods
The study included 72 full-thickness (2.5×2.5cm) wounds in 6 Yorkshire pigs. The wounds were grafted with autologous split-thickness skin grafts (meshed or sheet), placed either regularly (dermal-side-down) or inverted (dermal-side-up), and treated in wet or dry environment. Behavior of the skin grafts and healing were analyzed in histologies collected on days 4, 6, 9 and 12 postwounding. Wound contraction was quantified by photoplanimetry.
Results
In the wet environment, not only did inverted meshed skin grafts survive, but also they proliferated to accelerate reepithelialization. In this environment, wounds transplanted with inverted and regular meshed grafts showed no significant difference in reepithelialization rate and contraction. In contrast, in the dry environment, wounds transplanted with inverted meshed grafts showed a significantly lower reepithelialization and higher contraction than wounds transplanted with regular grafts. Inverted meshed grafts in dry environment and inverted sheet grafts did not survive.
Conclusions
The wound environment has an important role in the survival and proliferation of skin grafts, as demonstrated by survival of inverted meshed grafts in the wet environment and their contribution to accelerated reepithelialization, equal to the regularly placed grafts.
doi:10.1097/PRS.0b013e3181ccdc42
PMCID: PMC2848958  PMID: 20195112
13.  The Use of Growth Factors and Other Humoral Agents to Accelerate and Enhance Burn Wound Healing 
Eplasty  2011;11:e41.
Objective: Certain cytokines, especially those known as growth factors, have been demonstrated to mediate or modulate burn wound healing. Experimental and clinical evidence suggests that there are therapeutic advantages to the wound healing process when these agents are utilized. Positive effects have been reported for 4 types of wounds seen in the burn patient: partial-thickness wounds, full-thickness wounds, interstices of meshed skin grafts, and skin graft donor sites. Methods: A comprehensive literature search was performed using the MEDLINE, Ovid, and Web of Science databases to identify pertinent articles regarding growth factors and other cytokines in burns and wound healing. Results: The current knowledge about cytokine growth factors and their potential therapeutic applications in burn wound healing are discussed and reviewed. Conclusions: Platelet-derived growth factor, fibroblast growth factors, epidermal growth factors, transforming growth factor alpha, vascular endothelial growth factor, insulin-like growth factor I, nerve growth factor, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, and amnion-derived cellular cytokine solution have all been suggested to enhance the rate and quality of healing in 1 or more of these wounds encountered in burn care.
PMCID: PMC3212033  PMID: 22084646
14.  Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes 
Advances in Wound Care  2012;1(2):57-62.
Background
For patients suffering from catastrophic burns, few treatment options are available. Chimeric coculture of patient-derived autologous cells with a “carrier” cell source of allogeneic keratinocytes has been proposed as a means to address the complex clinical problem of severe skin loss.
The Problem
Currently, autologous keratinocytes are harvested, cultured, and expanded to form graftable epidermal sheets. However, epidermal sheets are thin, are extremely fragile, and do not possess barrier function, which only develops as skin stratifies and matures. Grafting is typically delayed for up to 4 weeks to propagate a sufficient quantity of the patient's cells for application to wound sites.
Basic/Clinical Science Advances
Fully stratified chimeric bioengineered skin substitutes could not only provide immediate wound coverage and restore barrier function, but would simultaneously deliver autologous keratinocytes to wounds. The ideal allogeneic cell source for this application would be an abundant supply of clinically evaluated, nontumorigenic, pathogen-free, human keratinocytes. To evaluate this potential cell-based therapy, mixed populations of a green fluorescent protein-labeled neonatal human keratinocyte cell line (NIKS) and unlabeled primary keratinocytes were used to model the allogeneic and autologous components of chimeric monolayer and organotypic cultures.
Clinical Care Relevance
Relatively few autologous keratinocytes may be required to produce fully stratified chimeric skin substitute tissue substantially composed of autologous keratinocyte-derived regions. The need for few autologous cells interspersed within an allogeneic “carrier” cell population may decrease cell expansion time, reducing the time to patient application.
Conclusion
This study provides proof of concept for utilizing NIKS keratinocytes as the allogeneic carrier for the generation of bioengineered chimeric skin substitute tissues capable of providing immediate wound coverage while simultaneously supplying autologous human cells for tissue regeneration.
doi:10.1089/wound.2011.0340
PMCID: PMC3839016  PMID: 24527281
15.  Mobilisation versus Bed Rest after Skin Grafting Pretibial Lacerations: A Meta-Analysis 
Plastic Surgery International  2012;2012:207452.
Pretibial lacerations are problematic and best managed by surgical debridement, then skin grafting. Traditional postoperative care involves bed rest to optimise graft survival. This meta-analysis assesses early mobilisation versus bed rest for skin graft healing of these wounds. Medline, Embase, Cochrane, Cinahl, and Google Scholar databases were searched. Analyses were performed on appropriate clinical trials. Four trials met with the inclusion criteria. No difference was demonstrated in split skin graft healing between patients mobilised early compared to patients admitted to hospital for postoperative bed rest at either 7 (OR 0.86 CI 0.29–2.56) or 14 days (OR 0.74 CI 0.31–1.79). There was a statistically significant delay in healing in patients treated with systemic corticosteroids (OR 8.20 CI 0.99–15.41). There was no difference in postoperative haematoma, bleeding, graft infection, or donor site healing between the comparison groups. In the available literature, there is no difference between early mobilisation and bed rest for the healing of skin grafts to pretibial wounds. Corticosteroids exert a negative effect on skin graft healing unlike early mobilisation, which does not cause increased haematoma, bleeding, infection, or delayed donor site healing. Modality of anaesthesia does not affect skin graft healing.
doi:10.1155/2012/207452
PMCID: PMC3335719  PMID: 22567252
16.  Management of Superficial to Partial-Thickness Wounds 
Journal of Athletic Training  2007;42(3):422-424.
Reference/Citation: Wiechula R. The use of moist wound-healing dressings in the management of split-thickness skin graft donor sites: a systematic review. Int J Nurs Pract. 2003; 9:S9–S17.
Clinical Question: Do rates of healing, infection, and pain differ depending on whether nonmoist or moist dressings are used to manage superficial to partial-thickness wounds?
Data Sources: Investigations were identified by CINAHL, MEDLINE, Pre-MEDLINE, Cochrane Library, Current Contents, Health STAR, EMBASE, Expanded Academic Index, and Dissertation Abstracts International searches. The search terms included skin, graft, and donor. Additional searches were performed with reference lists and bibliographies of retrieved studies.
Study Selection: To be included in the review, each study had to fulfill the following criteria: it had to be an intraindividual or prospective randomized controlled trial of human subjects; it had to include patients with postharvest split-thickness skin graft donor sites; it had to evaluate the effectiveness of primary and secondary wound dressings; and it had to have outcome measures that included healing (objective), infection (subjective), and pain (objective).
Data Extraction: Data extraction and study quality assessment procedures were developed specifically for this review based on Cochrane Collaboration, Centre for Reviews and Dissemination, and Joanna Briggs Institute protocols and were performed independently by the author. Details of the procedures were not fully explained. The principal outcome measures were healing (proportion of sites healed within the study period or time to complete healing), rate of infection, and pain scores. The studies were grouped according to broad dressing type (nonmoist and moist) and specific types of moist dressings (hydrocolloids and polyurethane semipermeable transparent films). When comparable, study results were pooled and analyzed with a fixed-effects model. Data within broader dressing categories (nonmoist and moist) were analyzed with a random-effects model. χ 2 analysis was used to determine heterogeneity among the studies. RevMan software (version 4.04; Cochrane Centre, Oxford, UK) was used for statistical analysis.
Main Results: The searches identified 111 studies and 1 integrative review, of which 58 studies met the inclusion and exclusion criteria. Inconsistency and variation in outcome measures and incomplete reporting of results prevented analysis of many studies. Wound healing was measured by days to complete healing (when dressings could be removed without trauma and pain) and wounds healed by day X (removal of dressings at regular intervals). Wound infection was subjectively measured based on clinical signs of infection (edema, heat, pain, or smell). Visual analog scales were used to measure pain levels.
Among the broad categories of nonmoist (sterile gauze, fine mesh gauze, Xerofoam [Tyco Healthcare Group LP, Mansfield, MA]) and moist (DuoDERM hydrocolloid [ConvaTec, Princeton, NJ], Tegaderm transparent film [3M Health Care, St Paul, MN], Opsite transparent film [Smith & Nephew, London, UK]) dressings, the outcomes of healing, infection, and pain were analyzed. In 6 studies, the findings significantly favored moist dressings, compared with nonmoist dressings, for days to complete healing (weighted mean difference [WMD] = −3.97, 95% confidence interval [CI] = −5.91, −2.02). In 9 studies, wounds healed by day X (day 7, 8, 9, 10, or 12) were analyzed. The results were varied and inconclusive because of a small number of trials and subjects. Among 10 studies, no significant difference was noted in infection rates between nonmoist and moist dressings (odds ratio [OR] = 0.41, 95% CI = 0.14, 1.18). Three studies using visual analog scales for the outcome of pain were converted into a uniform scale of 1 to 10 (10 representing most painful). The findings significantly favored moist dressings over nonmoist dressings (WMD = −1.75, 95% CI = −2.94, −0.56).
Among nonmoist and specific types of moist dressings, a subset analysis was performed to examine the outcomes of healing, infection, and pain. For days to complete healing, 2 investigations significantly favored hydrocolloid dressings over nonmoist dressings (WMD = −2.19, 95% CI = −2.89, −1.49). Additionally, in 2 studies, hydrocolloid dressings were significantly favored over other moist dressings (semiocclusive hydrocolloid and transparent film) for days to complete healing (WMD = −1.45, 95% CI = −2.17, −0.74). In 3 studies, the data significantly favored polyurethane semipermeable transparent film dressings over nonmoist dressings for days to complete healing (WMD = −2.82, 95% CI = −3.58, −2.07). For infection rates, 4 studies significantly favored hydrocolloid dressings over nonmoist dressings (OR = 0.21, 95% CI = 0.07, 0.65). In 4 other studies, polyurethane semipermeable transparent film dressings were significantly favored over nonmoist dressings with regard to infection rates (OR = 0.28, 95% CI = 0.09, 0.91). For the outcome of pain, varied outcome measures and insufficient data prevented analysis among specific types of moist dressings.
Conclusions: Moist dressings decreased the days to complete healing and pain scores when compared with nonmoist dressings. Among the broad categories of nonmoist and moist dressings, no differences were found in infection rates. The data on specific types of moist dressings revealed that days to complete healing were decreased with hydrocolloid dressings compared with nonmoist and other moist dressings. Hydrocolloid dressings also decreased infection rates compared with nonmoist dressings. Polyurethane semipermeable transparent film dressings also decreased days to complete healing and infection rates compared with nonmoist dressings. Overall, the data indicated that hydrocolloid dressings are more effective than nonmoist dressings in terms of rates of healing, infection, and pain in the management of superficial to partial-thickness wounds. The variations in outcome measures among the included studies should be considered in interpreting these findings.
PMCID: PMC1978464  PMID: 18059999
moist dressings; abrasions
17.  PA01.39. A clinical study in the management of dustavrana with balataila application 
Ancient Science of Life  2012;32(Suppl 1):S89.
Purpose:
Proper care must be taken even for a clean wound in normal body to heal earlier with a minimum scar. Various scientific and technological advancement taking place from time to time the problem wound healing is still under evolution process, till now there are many research works have been undertaken on Chronic wounds. As Dustavrana is vitiated by various doshas so it needs proper care in proper time. Hence in present concept all efforts are directed to keep the wound clean and also to enhance the wound healing. To manage the Dustavrana different type of treatment modalities explained in the classics, Bala Taila is one among them. Objective of study: To assess the effectiveness of BalaTaila Application in wound healing. To assess the healing of wound (Vrana ropana).
Method:
30 patients were selected according to inclusion criteria and divided into two groups of 15 each. Viz Group I: Trail group, were treated by Bala Taila local application once daily & Group II: Control group, were treated by the application of Hydrogen Peroxyde, sterile dry gauze were used for dressing.
Result:
Results were assessed with the help of prefixed assessment criteria, and favorable results obtained on, Vedana as 85%, Swelling 80%, Varna 84.44%, Srava 82.92% Granulation 86.66% and size of wound 79.41%. The result of Bala Taila is found to be statically significant in the process of wound healing
Conclusion:
The Bala Taila proves a vital role in the healing of Dustavrana.
PMCID: PMC3800971
18.  Effect of Mixed Transplantation of Autologous and Allogeneic Microskin Grafts on Wound Healing in a Rat Model of Acute Skin Defect 
PLoS ONE  2014;9(1):e85672.
The treatment of extensive thermal injuries with insufficient autologous skin remains a great challenge to burn surgeons. In this study, we investigated the influence of the ratio of autologous and allogeneic tissue in mixed microskin grafts on wound healing in order to develop an effective method for using limited donor skin to cover a large open wound. Four different mixtures were tested: autologous microskin at an area expansion ratio of 10∶1 with allogeneic microskin at an area expansion ratio of 10∶1 or 10∶3 and autologous microskin at an expansion ratio of 20∶1 with allogeneic microskin at an expansion ratio of 20∶3 or 20∶6. Wound healing, wound contraction, and integrin β1 expression were measured. Mixed microskin grafting facilitated wound healing substantially. The mixture of autologous microskin at an expansion ratio of 10∶1 with the same amount of allogeneic microskin achieved the most satisfactory wound healing among the 4 tested mixtures. Histological examination revealed the presence of obviously thickened epidermis and ectopic integrin β1 expression. Keratinocytes expressing integrin β1 were scattered in the suprabasal layer. Higher levels of integrin β1 expression were associated with faster wound healing, implying that ectopic expression of integrin β1 in keratinocytes may play a pivotal role in wound healing. In conclusion, this study proves that this new skin grafting technique may improve wound healing.
doi:10.1371/journal.pone.0085672
PMCID: PMC3897459  PMID: 24465646
19.  Dressings and Products in Pediatric Wound Care 
Advances in Wound Care  2014;3(4):324-334.
Significance: The increasing complexity of medical and surgical care provided to pediatric patients has resulted in a population at significant risk for complications such as pressure ulcers, nonhealing surgical wounds, and moisture-associated skin damage. Wound care practices for neonatal and pediatric patients, including the choice of specific dressings or other wound care products, are currently based on a combination of provider experience and preference and a small number of published clinical guidelines based on expert opinion; rigorous evidence-based clinical guidelines for wound management in these populations is lacking.
Recent Advances: Advances in the understanding of the pathophysiology of wound healing have contributed to an ever-increasing number of specialized wound care products, most of which are predominantly marketed to adult patients and that have not been evaluated for safety and efficacy in the neonatal and pediatric populations. This review aims to discuss the available data on the use of both more traditional wound care products and newer wound care technologies in these populations, including medical-grade honey, nanocrystalline silver, and soft silicone-based adhesive technology.
Critical Issues: Evidence-based wound care practices and demonstration of the safety, efficacy, and appropriate utilization of available wound care dressings and products in the neonatal and pediatric populations should be established to address specific concerns regarding wound management in these populations.
Future Directions: The creation and implementation of evidence-based guidelines for the treatment of common wounds in the neonatal and pediatric populations is essential. In addition to an evaluation of currently marketed wound care dressings and products used in the adult population, newer wound care technologies should also be evaluated for use in neonates and children. In addition, further investigation of the specific pathophysiology of wound healing in neonates and children is indicated to promote the development of wound care dressings and products with specific applications in these populations.
doi:10.1089/wound.2013.0477
PMCID: PMC3985526  PMID: 24761363
20.  Salvage of Failed Local and Regional Flaps with Porcine Urinary Bladder Extracellular Matrix Aided Tissue Regeneration 
Case Reports in Otolaryngology  2013;2013:917183.
Local and regional flap failure can be a major complication in head and neck surgery, which continue to be prevalent for a number of reasons including poor flap design, improper surgical technique, and poor tissue vascularity. Dealing with these failures can be quite difficult. Surgical debridement, flap revisions, and complex wound regimens are necessitated to reestablish appropriate tissue coverage. Traditional use of wet to dry dressing to enable proper wound granulation and possible closure with additional flaps or skin grafts is a laborious process. Such treatments place great time burdens on the patient, physicians, and nurses. Because the face and neck possess a complex three-dimensional topography, wound dressings are inherently complex to design and change. Many patients also require postoperative treatments such as radiation and chemotherapy to treat aggressive malignancies, and delay in wound healing leads to a delay in adjuvant treatment. Recently, advances in regenerative medicine, specifically xenogeneic extracellular matrix compounds, have been shown to promote tissue growth while limiting scar tissue formation (Badylak 2004). To our knowledge, this paper is the first case series using the porcine extracellular matrix bioscaffold (MatriStem ACell, Columbia, MD, USA) to salvage flaps with extensive wound breakdown on the face and neck.
doi:10.1155/2013/917183
PMCID: PMC3804044  PMID: 24191216
21.  A comparative analysis of advanced techniques for skin reconstruction with autologous keratinocyte culture in severely burned children: own experience 
Introduction
The local treatment in burns larger than 50% of total body surface area is still the great challenge for surgeons.
Aim
This paper presents a review of different solutions for deep burn wound healing in children and the early outcomes of treatment with combined autologous cell culture technique.
Material and methods
For this study, 20 children aged between 4 and 12 years with 55–65% of TBSA III grade burn injury were analyzed. A skin sample, 1 cm × 1 cm in size, for keratinocyte cultivation, was taken on the day of the burn. After necrotic tissue excision, the covering of the burned area with an isolated meshed skin graft was carried out between day 4 and 7. After 7 days of keratinocyte cultivation, the mentioned areas were covered with cells from the culture. We divided the burned regions, according to the way of wound closure, into 3 groups each consisting of 15 treated regions of the body. We used meshed split thickness skin grafts (SSG group), cultured autologous keratinocytes (CAC group), and both techniques applied in one stage (SSG + CAC group).
Results
In the SSG group, the mean time for complete closure of wounds was 12.7 days. Wounds treated with CAC only needed a non-significantly longer time to heal – 14.2 days (p = 0.056) when compared to SSG. The shortest time to heal was observed in the group treated with SSG + CAC – 8.5 days, and it was significantly shorter when compared to the SSG and CAC groups (p < 0.001).
Conclusions
This study suggests that cultured keratinocytes obtained after short-time multiplication, combined with meshed autologous split thickness skin grafts, constitute the optimal wound closure in burned children.
doi:10.5114/pdia.2014.43190
PMCID: PMC4112268  PMID: 25097488
burn; skin graft; meshed graft; skin cell culture
22.  Application of acellular dermal xenografts in full-thickness skin burns 
The aim of this study was to explore the clinical value of the porcine acellular dermal xenograft (ADX) in combination with autologous split-thickness skin and pure autologous split-thickness skin grafting applied in deep full-thickness burns and scar wounds. A total of 30 patients with deep burns were randomly divided into experimental and control groups following escharectomy. The patients were separately treated with porcine acellular dermal xenograft (ADX) in combination with autologous split-thickness skin and pure autologous split-thickness skin graft. The wound healing was observed routinely and the scores were evaluated using Vancouver scar scale at different times following transplant surgery. The samples of cograft regions and the control group (pure transplant split-thickness skin autograft) were observed using light microscopy and electron microscopy, and the follow-up results were recorded. No conspicuous rejections on the cograft wound surface were observed. Compared with the control group, the cograft wounds were smooth, presented no scar contracture and exhibited good skin elasticity and recovery of the joint function. The cografted skin combined well and displayed a clear and continuous basal membrane, as well as gradually combined skin structure, a mature stratum corneum, downward extended rete pegs, a mainly uniform dermal collagen fiber structure, regular alignment, and fewer blood capillaries. Clear desmosome cograft regions were identified among heckle cells, as well as a clear and continuous basal membrane. The cografted skin of the combined split-thickness autograft and the acellular heterologous (porcine) dermal matrix showed an improved shape and functional recovery compared with the pure split-thickness skin autograft. The combination of the meshed ADX and the split-thickness skin autograft applied in deep full-thickness burns and scar wounds may induce tissue regeneration via dermis aiming. This method also has superior shape and functional recovery, and has an extensive clinical application value.
doi:10.3892/etm.2013.1114
PMCID: PMC3735587  PMID: 23935745
skin grafting; burns; slit-thickness skin; acellular dermal xenograft
23.  Unusual Donor Sites for Harvesting of Island Skin Grafts 
Summary
This study reports on the use of two unusual donor sites for the harvesting of island skin grafts used in the coverage of large skin wounds. Island grafts were taken not only from intact skin but also from itself and from newly generated epithelium, so that it could be transferred to another defect area. The study included 23 patients with skin wounds of different sizes due to burn injury (17 patients) and traffic accidents (6 cases). After granulation tissue had taken on the wound surface, island grafts (area 1 to 2 cm2) were harvested from three donor sites and placed over the wound 1 to 3 cm apart. The granulation tissue around the grafts was covered by the epithelium spreading from the island grafts, with the wounds closing in two to seven weeks, depending on their size. Donor areas healed spontaneously, with epithelialization in one to three weeks. Utilizing the new donor sites as a source of epithelium, island grafts may become a new alternative to other skin graft techniques in patients who have limited donor sites or who do not want any more donor site scars.
PMCID: PMC3188200  PMID: 21991139
DONOR; SITES; HARVESTING; ISLAND; SKIN GRAFTS
24.  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.
doi:10.4103/0970-0358.101304
PMCID: PMC3495381  PMID: 23162230
Limited access dressing; negative pressure wound therapy; suction-assisted dressing
25.  Management of Chronic Pressure Ulcers 
Executive Summary
In April 2008, the Medical Advisory Secretariat began an evidence-based review of the literature concerning pressure ulcers.
Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/tech/tech_mn.html to review these titles that are currently available within the Pressure Ulcers series.
Pressure ulcer prevention: an evidence based analysis
The cost-effectiveness of prevention strategies for pressure ulcers in long-term care homes in Ontario: projections of the Ontario Pressure Ulcer Model (field evaluation)
Management of chronic pressure ulcers: an evidence-based analysis
Objective
The Medical Advisory Secretariat (MAS) conducted a systematic review on interventions used to treat pressure ulcers in order to answer the following questions:
Do currently available interventions for the treatment of pressure ulcers increase the healing rate of pressure ulcers compared with standard care, a placebo, or other similar interventions?
Within each category of intervention, which one is most effective in promoting the healing of existing pressure ulcers?
Background
A pressure ulcer is a localized injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure, or pressure in conjunction with shear and/or friction. Many areas of the body, especially the sacrum and the heel, are prone to the development of pressure ulcers. People with impaired mobility (e.g., stroke or spinal cord injury patients) are most vulnerable to pressure ulcers. Other factors that predispose people to pressure ulcer formation are poor nutrition, poor sensation, urinary and fecal incontinence, and poor overall physical and mental health.
The prevalence of pressure ulcers in Ontario has been estimated to range from a median of 22.1% in community settings to a median of 29.9% in nonacute care facilities. Pressure ulcers have been shown to increase the risk of mortality among geriatric patients by as much as 400%, to increase the frequency and duration of hospitalization, and to decrease the quality of life of affected patients. The cost of treating pressure ulcers has been estimated at approximately $9,000 (Cdn) per patient per month in the community setting. Considering the high prevalence of pressure ulcers in the Ontario health care system, the total cost of treating pressure ulcers is substantial.
Technology
Wounds normally heal in 3 phases (inflammatory phase, a proliferative phase of new tissue and matrix formation, and a remodelling phase). However, pressure ulcers often fail to progress past the inflammatory stage. Current practice for treating pressure ulcers includes treating the underlying causes, debridement to remove necrotic tissues and contaminated tissues, dressings to provide a moist wound environment and to manage exudates, devices and frequent turning of patients to provide pressure relief, topical applications of biologic agents, and nutritional support to correct nutritional deficiencies. A variety of adjunctive physical therapies are also in use.
Method
Health technology assessment databases and medical databases were searched from 1996 (Medline), 1980 (EMBASE), and 1982 (CINAHL) systematically up to March 2008 to identify randomized controlled trials (RCTs) on the following treatments of pressure ulcers: cleansing, debridement, dressings, biological therapies, pressure-relieving devices, physical therapies, nutritional therapies, and multidisciplinary wound care teams. Full literature search strategies are reported in appendix 1. English-language studies in previous systematic reviews and studies published since the last systematic review were included if they had more than 10 subjects, were randomized, and provided objective outcome measures on the healing of pressure ulcers. In the absence of RCTs, studies of the highest level of evidence available were included. Studies on wounds other than pressure ulcers and on surgical treatment of pressure ulcers were excluded. A total of 18 systematic reviews, 104 RCTs, and 4 observational studies were included in this review.
Data were extracted from studies using standardized forms. The quality of individual studies was assessed based on adequacy of randomization, concealment of treatment allocation, comparability of groups, blinded assessment, and intention-to-treat analysis. Meta-analysis to estimate the relative risk (RR) or weighted mean difference (WMD) for measures of healing was performed when appropriate. A descriptive synthesis was provided where pooled analysis was not appropriate or not feasible. The quality of the overall evidence on each intervention was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) criteria.
Findings
Findings from the analysis of the included studies are summarized below:
Cleansing
There is no good trial evidence to support the use of any particular wound cleansing solution or technique for pressure ulcers.
Debridement
There was no evidence that debridement using collagenase, dextranomer, cadexomer iodine, or maggots significantly improved complete healing compared with placebo.
There were no statistically significant differences between enzymatic or mechanical debridement agents with the following exceptions:
Papain urea resulted in better debridement than collagenase.
Calcium alginate resulted in a greater reduction in ulcer size compared to dextranomer.
Adding streptokinase/streptodornase to hydrogel resulted in faster debridement.
Maggot debridement resulted in more complete debridement than conventional treatment.
There is limited evidence on the healing effects of debridement devices.
Dressings
Hydrocolloid dressing was associated with almost three-times more complete healing compared with saline gauze.
There is evidence that hydrogel and hydropolymer may be associated with 50% to 70% more complete healing of pressure ulcers than hydrocolloid dressing.
No statistically significant differences in complete healing were detected among other modern dressings.
There is evidence that polyurethane foam dressings and hydrocellular dressings are more absorbent and easier to remove than hydrocolloid dressings in ulcers with moderate to high exudates.
In deeper ulcers (stage III and IV), the use of alginate with hydrocolloid resulted in significantly greater reduction in the size of the ulcers compared to hydrocolloid alone.
Studies on sustained silver-releasing dressing demonstrated a tendency for reducing the risk of infection and promoting faster healing, but the sample sizes were too small for statistical analysis or for drawing conclusions.
Biological Therapies
The efficacy of platelet-derived growth factors (PDGFs), fibroblast growth factor, and granulocyte-macrophage colony stimulating factor in improving complete healing of chronic pressure ulcers has not been established.
Presently only Regranex, a recombinant PDGF, has been approved by Health Canada and only for treatment of diabetic ulcers in the lower extremities.
A March 2008 US Food and Drug Administration (FDA) communication reported increased deaths from cancers in people given three or more prescriptions for Regranex.
Limited low-quality evidence on skin matrix and engineered skin equivalent suggests a potential role for these products in healing refractory advanced chronic pressure ulcers, but the evidence is insufficient to draw a conclusion.
Adjunctive Physical Therapy
There is evidence that electrical stimulation may result in a significantly greater reduction in the surface area and more complete healing of stage II to IV ulcers compared with sham therapy. No conclusion on the efficacy of electrotherapy can be drawn because of significant statistical heterogeneity, small sample sizes, and methodological flaws.
The efficacy of other adjunctive physical therapies [electromagnetic therapy, low-level laser (LLL) therapy, ultrasound therapy, ultraviolet light therapy, and negative pressure therapy] in improving complete closure of pressure ulcers has not been established.
Nutrition Therapy
Supplementation with 15 grams of hydrolyzed protein 3 times daily did not affect complete healing but resulted in a 2-fold improvement in Pressure Ulcer Scale for Healing (PUSH) score compared with placebo.
Supplementation with 200 mg of zinc three times per day did not have any significant impact on the healing of pressure ulcers compared with a placebo.
Supplementation of 500 mg ascorbic acid twice daily was associated with a significantly greater decrease in the size of the ulcer compared with a placebo but did not have any significant impact on healing when compared with supplementation of 10 mg ascorbic acid three times daily.
A very high protein tube feeding (25% of energy as protein) resulted in a greater reduction in ulcer area in institutionalized tube-fed patients compared with a high protein tube feeding (16% of energy as protein).
Multinutrient supplements that contain zinc, arginine, and vitamin C were associated with a greater reduction in the area of the ulcers compared with standard hospital diet or to a standard supplement without zinc, arginine, or vitamin C.
Firm conclusions cannot be drawn because of methodological flaws and small sample sizes.
Multidisciplinary Wound Care Teams
The only RCT suggests that multidisciplinary wound care teams may significantly improve healing in the acute care setting in 8 weeks and may significantly shorten the length of hospitalization. However, since only an abstract is available, study biases cannot be assessed and no conclusions can be drawn on the quality of this evidence.
PMCID: PMC3377577  PMID: 23074533

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