Management of Acute Wounds - Expert Panel Consensus Statement.

SIGNIFICANCE: The Wound Healing Foundation recognized the need for consensus-based unbiased recommendations for the treatment of wounds. As a first step, a consensus on the treatment of chronic wounds was developed and published in 2022.(1) The current publication on acute wounds represents the second step in this process. Acute wounds may result from any number of conditions, including burns, military and combat operations, and trauma to specific areas of the body. The management of acute wounds requires timely and evidence-driven intervention to achieve optimal clinical outcomes. This consensus statement provides the clinician with the necessary foundational approaches to the causes, diagnosis and therapeutic management of acute wounds. Presented in a structured format, this is a useful guide for clinicians and learners in all patient care settings. RECENT ADVANCES: Recent advances in the management of acute wounds have centered on stabilization and treatment in the military and combat environment, Specifically advancements in hemostasis, resuscitation, and the mitigation of infection risk through timely initiation of antibiotics and avoidance of high pressure irrigation in contaminated soft tissue injury. . CRITICAL ISSUES: Critical issues include infection control, pain management and the unique considerations for the management of acute wounds in pediatric patients. FUTURE DIRECTIONS: Future directions include new approaches to preventing the progression and conversion of burns through the use of the microcapillary gel, a topical gel embedded with the anti-inflammatory drug infliximab.(38) Additionally, the use of three-dimensional bioprinting and photo-modulation for skin reconstruction following burns is a promising area for continued discovery.

Split-Thickness Skin and Dermal Pixel Grafts Can Be Expanded up to 500 Times to Re-Epithelialize a Full-Thickness Burn Wound.

Objective: Autologous skin transplantation is limited by donor site availability for patients with extensive burns. The objective of this study was to demonstrate the feasibility and efficacy of split-thickness skin (STS) and dermal pixel grafts (PG) in the treatment of burns. Approach: The study was divided into three arms of validation, expansion, and combination that all followed the same study design. Sixteen deep partial-thickness burns were created on the dorsum of anesthetized pigs. Three days postinjury the burns were debrided and grafted with STS and dermal PGs. The PGs were prepared by harvesting two skin grafts (split-thickness skin graft [STSG] and dermal graft) from the same donor site going down in depth. The grafts were minced to 0.3 × 0.3 × 0.3 mm PGs and suspended in a small volume of hydrogel. Healing was monitored for 6, 10, 14, or 28 days. In the validation study the PGs at 1:2 expansion ratio were transplanted and compared with STSG and untreated controls. The expansion study investigated the maximum expansion potential of the PGs and the combination of the benefits of transplanting STS and dermal PGs together. Results: The validation study showed that when STS and dermal PGs were transplanted in a 1:2 ratio they fully re-epithelialized the wounds in 14 days. The expansion study demonstrated that using expansion ratios up to 1:500 the wounds were re-epithelialized by day 28. The combination study showed that there was no additional benefit to use STS and dermal PGs together. Innovation: Pixel grafting provides expansion ratios greater than conventional STSG. The possibility to harvest both STS and dermal PGs from the same donor area further reduces the need for healthy skin. Conclusion: STSG and dermal grafts can be minced to PGs with preserved viability and expanded up to 500 times to re-epithelialize a wound.

Minced skin grafts for chronic wounds compared to conventional mesh grafts.

Background and Aims: Skin grafting is the single most effective method to close a chronic wound. The current standard of care is to use meshed split thickness skin grafts. This entails the use of surgical instruments that need to be autoclaved and to have a power source, which usually requires an OR facility. The minced skin technique uses single use, presterilized instruments and the procedure can be done under local anesthesia, by a wound care practitioner, in a wound clinic, a physician's office or even at the bedside. The current study was designed to determine if the results from micrografting were non inferior to conventional mesh grafting. Methods: In a prospective non inferiority study, 26 chronic ulcers were treated with micrografting (MSG) and 24 with conventional mesh grafts 1:3 (control group-CG) in a total of 21 patients, 10 male and 11 female. The donor site areas in the MSG group were predetermined to 2.5 × 5 cm and the mesh grafts expansion was set at 1:3. Results: In the first weeks postoperatively, micrograft healing initially lagged behind the conventional mesh grafts but at 60 days after grafting, all MSG wounds were healed. The MSG wounds had better pigmentation, less itching, and less scarring. The micrografting procedure was easy to learn and expeditious to perform. The MSG mean expansion was 9.1 compared to three times (CG). Conclusion: The MSG procedure is not inferior to conventional mesh grafting, requires smaller donor sites, and can be done with single use instruments, under local anesthesia, with early discharge.

Topical Drug Delivery in the Treatment of Skin Wounds and Ocular Trauma Using the Platform Wound Device.

Topical treatment of injuries such as skin wounds and ocular trauma is the favored route of administration. Local drug delivery systems can be applied directly to the injured area, and their properties for releasing therapeutics can be tailored. Topical treatment also reduces the risk of adverse systemic effects while providing very high therapeutic concentrations at the target site. This review article highlights the Platform Wound Device (PWD) (Applied Tissue Technologies LLC, Hingham, MA, USA) for topical drug delivery in the treatment of skin wounds and eye injuries. The PWD is a unique, single-component, impermeable, polyurethane dressing that can be applied immediately after injury to provide a protective dressing and a tool for precise topical delivery of drugs such as analgesics and antibiotics. The use of the PWD as a topical drug delivery platform has been extensively validated in the treatment of skin and eye injuries. The purpose of this article is to summarize the findings from these preclinical and clinical studies.

Delivery of topical gentamicin cream via platform wound device to reduce wound infection-A prospective, controlled, randomised, clinical study.

The platform wound device (PWD) is a wound coverage system that is designed to decrease wound infection rates by allowing for direct delivery of topical antibiotics and antimicrobials while creating a sealed, protective barrier around the area of injury. This study evaluated the safety and efficacy of the PWD as a protective dressing and a delivery system for topical antibiotics compared to the current standard of care (SoC). This was a multi-center, prospective, randomised, controlled clinical trial. The wounds were treated with the PWD with gentamicin cream or SoC dressings. The wounds were evaluated before the start of treatment and after 48-96 hours via clinical assessment, photographs, and qualitative bacterial swabs for bacterial analysis. The delivery of gentamicin via the PWD was safe and did not cause any adverse effects. The treatment decreased both inflammation and bacterial growth during the study period. No significant differences in the SoC were observed. The PWD is a transparent and impermeable polyurethane chamber that encloses and protects the injured area. The delivery of topical gentamicin via the PWD was safe and effective. Clinical assessment for infection found the PWD to be non-inferior to the current SoC treatment options.

Chronic wounds: Treatment consensus.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs. Eighty percent or better concurrence among the panellists was considered a consensus. A large number of critical questions were discussed and agreed upon. Important takeaways included that wound care needs to be simplified to a point that it can be delivered by the patient or the patient's family. Another one was that telemonitoring, which has proved very useful during the COVID-19 pandemic, can help reduce the frequency of interventions by a visiting nurse or a wound care center. Defining patient expectations is critical to designing a successful treatment. Patient outcomes might include wound specific outcomes such as time to heal, wound size reduction, as well as improvement in quality of life. For those patients with expectations of healing, an aggressive approach to achieve that goal is recommended. When healing is not an expectation, such as in patients receiving palliative wound care, outcomes might include pain reduction, exudate management, odour management and/or other quality of life benefits to wound care.

Wound care research sponsored by the Department of Defense.

Due to the need for more information about Department of Defense sponsored wound healing research, the Wound Healing Foundation initiated the writing of this article. It briefly describes the Vision, Mission and Goals of the Department of Defense Strategic Medical Research Plan. It also describes the current objectives of Department of Defense research funding and where to access this information in detail. The grant cycle, the timing of request for proposals and some of the specifics of their requirements are also mentioned. A brief discussion of budgeting and overhead is also included.

Utilization of a Novel Negative Pressure Platform Wound Dressing on Surgical Incisions: A Case Series.

Closed incision negative pressure therapy (ciNPT) has been shown to improve wound healing for patients at high risk for wound complications. Current devices consist of opaque interface dressings that do not allow ongoing visual evaluation of the surgical incision and utilize a negative pressure of -80 mm Hg to -125 mm Hg. The Negative Pressure Platform Wound Dressing (NP-PWD) was developed to address these aspects. This case series is the first evaluation of the NP-PWD in a clinical setting. METHODS: Patients aged 18-85 undergoing an operation with an anticipated incision and primary closure were screened. Demographics, comorbidities, and operation performed were recorded. Following closure, the incision was measured and photographed before NP-PWD placement. The NP-PWD was removed at the first postoperative check (POC) between postoperative days (PODs) 3-5. Subjects were followed until PODs 9-14. POCs consisted of incision assessment, measurement, photography, and adverse event monitoring. RESULTS: A total of 8 patients with 10 incisions were included in the study. Five patients were men. Median age was 56 years (IQR 53-74 years). All incisions were intact and without inflammation or infection at all POCs. Three adverse events, including small blisters and interruption of therapy, were noted. CONCLUSIONS: This case series reports that patients tolerated the NP-PWD on closed surgical incisions well and that all incisions were intact without evidence of inflammation or infection after 2 weeks of follow-up. Future controlled, clinical studies should further examine the safety and efficacy of the use of the NP-PWD.

Human platelet lysate delivered via an ocular wound chamber for the treatment of corneal epithelial injuries.

Current strategies to address corneal surface defects are insufficient to successfully resolve damage caused by injury and/or disease. To address this issue, we have developed an ocular wound chamber (OWC) that creates a fluid-filled environment by encompassing damaged ocular and periocular tissues allowing for the continuous delivery of therapeutics. This study tested human platelet lysate (hPL) as a treatment for corneal epithelial defects when used with the OWC. Corneal epithelial injuries were created in anesthetized guinea pigs by debridement of the central cornea. An OWC was placed over the injured eye and animals randomly grouped followed by injection of either 20% hPL, 100% hPL, or vehicle (balanced salt solution, BSS) into the chamber. Eyes were assessed at 0, 24, 48, and 72 h using intraocular pressure (IOP), optical coherence tomography (OCT), and fluorescein imaging. Whole globes were histologically processed, and hematoxylin and eosin (H&E) stained. No differences in IOP were recorded as a result of corneal wounding, chamber placement, and/or therapeutic application. OCT images demonstrated increased corneal swelling at 48 h and 72 h in the vehicle group compared to 20% hPL. Fluorescein staining showed increased corneal re-epithelialization in the 20% and 100% hPL groups at 48 h compared to vehicle only. H&E staining revealed increased stromal cellular infiltrate in the BSS group. This study demonstrates the delivery of hPL via the OWC improves corneal re-epithelialization and supports the expanded usage of the chamber in combination with hPL to manage a variety of corneal surface injuries, diseases and/or periocular conditions.

Moist Wound Healing with Commonly Available Dressings.

Significance: A moist wound environment has several benefits that result in faster and better quality of healing. It facilitates autolytic debridement, reduces pain, reduces scarring, activates collagen synthesis, facilitates and promotes keratinocyte migration over the wound surface, and supports the presence and function of nutrients, growth factors, and other soluble mediators in the wound microenvironment. Recent Advances: Wound dressings can be utilized to create, maintain, and control a moist environment for healing. Moist wound dressings can be divided into films, foams, hydrocolloids, hydrogels, and alginates. We are also including negative pressure wound therapy systems in the moist dressings. Critical Issues: An optimal wound dressing should provide a moist environment and have an optimal water vapor transmission rate (WVTR) and absorptive capacity. It should also protect the wound against trauma and contamination and be easy to apply, painless to remove, and esthetically acceptable or even pleasing. Future Directions: Interventions, particularly dressing changes, by medical caregivers are labor intensive and expensive and there should be a continuous effort to reduce their number per week. Smart dressings with integrated microsensors and delivery capabilities that would allow wireless real-time monitoring and treatment of the wound would be very advantageous. This way the state of the wound as well as the wear time of the dressing could be assessed without dressing removal or visit to the wound care center. In addition, an ability to adjust the WVTRs to the exudate level of the wound (or having a large absorptive capacity without changing the WVTR) would be useful. This feature would guarantee an optimal level of hydration of the wound surface throughout the treatment.

Study Comparing Platform Wound Dressing, a Negative-Pressure Device without a Filler, with Three Conventional Negative-Pressure Wound Therapy Systems in the Treatment of Excisional and Incisional Wounds.

BACKGROUND: All common negative-pressure wound therapy systems include a material, usually foam or gauze, at the wound/device interface. In this preclinical study, the authors have compared the effects on different wound healing parameters in the three most common negative-pressure wound therapy systems (i.e., V.A.C.VIA, PREVENA, and PICO) with a new device without foam or gauze (i.e., Platform Wound Dressing). A strong effort was made to avoid bias. The study was conducted under good laboratory practice conditions, with the presence of an independent observer. METHODS: In pigs, three types of wounds were studied: full-thickness excisions, open incisions, and sutured closed incisions. Several macroscopic and microscopic parameters were studied. The pigs were euthanized on day 9 and all wounds were processed for histology and excisions for immunohistochemistry. RESULTS: In general, the devices produced similar results, with only a few significant differences. In the excisions, the Platform Wound Dressing reduced wound area more than the V.A.C.VIA and the PICO. In the excisional wounds, reepithelialization was the same. In open incisions, PREVENA was better than the Platform Wound Dressing. Histologic examination showed that, in open incisions, there was less inflammation in the PREVENA-treated in comparison with the Platform Wound Dressing- and the PICO-treated wounds. Immunohistochemical analyses showed that the Platform Wound Dressing-treated excisions had significantly more blood vessels (von Willebrand factor) than the V.A.C.VIA-treated ones and that the PICO caused less T-cell activation (CD3) than the other two. CONCLUSION: The devices-with foam, with gauze, or without either and just an embossed membrane-performed equally in general.

Treatment of Corneal Infections Utilizing an Ocular Wound Chamber.

Purpose: To demonstrate that the ocular wound chamber (OWC) can be used for the treatment of bacterial keratitis (BK). Methods: A blepharotomy was performed on anesthetized, hairless guinea pigs to induce exposure keratopathy 72 hours before corneal wound creation and Pseudomonas aeruginosa inoculation. Twenty-four hours postinoculation, eyes were treated with an OWC filled with 500 µL 0.5% moxifloxacin hydrochloride ophthalmic solution (OWC), 10 µL 0.5% moxifloxacin hydrochloride drops (DROPS) four times daily, or not treated (NT). White light, fluorescein, and spectral domain optical coherence tomography (SD-OCT) images; ocular and periocular tissues samples for colony-forming units (CFU) quantification; and plasma samples were collected at 24 and 72 hours posttreatment. Results: White light, fluorescein, and SD-OCT imaging suggests OWC-treated eyes are qualitatively healthier than those in DROPS or NT groups. At 24 hours, the median number of CFUs (interquartile range) measured was 0 (0-8750), 150,000 (106,750-181,250), and 8750 (2525-16,000) CFU/mL for OWC, NT, and DROPS, respectively. While 100% of NT and DROPS animals remained infected at 24 hours, only 25% of OWC-treated animals showed infection. Skin samples at 24 hours showed infection percentages of 50%, 75%, and 0% in DROPS, NT, and OWC groups, respectively. OWC-treated animals had higher moxifloxacin plasma concentrations at 24 and 72 hours than those treated with drops. Conclusions: OWC use resulted in a more rapid decrease of CFUs when compared to DROPS or NT groups and was associated with qualitatively healthier ocular and periocular tissue. Translational Relevance: The OWC could be used clinically to continuously and rapidly deliver antimicrobials to infected ocular and periocular tissues, effectively lowering bacterial bioburdens and mitigating long-term complications.

Immediate Treatment of Burn Wounds with High Concentrations of Topical Antibiotics in an Alginate Hydrogel Using a Platform Wound Device.

Objective: There is an unmet need to improve immediate burn care, particularly when definitive treatment is delayed. Therefore, the purpose of this project was to formulate a hydrogel that contains very high concentrations of antibiotics and validate its use together with a platform wound device (PWD) for the immediate care of burns. Approach: The hydrogel properties were optimized by using a rheometer, differential scanning calorimetry, and liquid chromatography-mass spectrometry and were tested in an infected porcine burn model. Immediately, after burn creation, the burns were infected with different bacteria. Subsequently, the burns infected with Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii were covered with the PWD and treated with a single dose of hydrogel containing 1000 × minimum inhibitory concentration of vancomycin, gentamicin, and minocycline, respectively. On day 7 or 45, the animals were euthanized, and the burns were harvested for histology and quantitative bacteriology. Results: 0.625% was the best alginate concentration for the hydrogel in terms of viscosity, stability, and drug release. The porcine studies demonstrated that vancomycin-, gentamicin-, and minocycline-treated tissues contained significantly less bacteria and reduced depth of tissue necrosis in comparison to controls. Innovation: The PWD represents a platform technology that begins at the point of the first treatment by protecting the wound and allowing administration of topical therapeutics. The device can be adapted to enclose any size burn over any contour of the body. Conclusion: Antibiotics can be delivered safely in very high concentrations in a hydrogel using the PWD, and burn infections can be treated successfully with this method.

Antibiotic-Containing Agarose Hydrogel for Wound and Burn Care.

Wound infections cause inflammation, tissue damage, and delayed healing that can lead to invasive infection and even death. The efficacy of systemic antibiotics is limited due to poor tissue penetration that is especially a problem in burn and blast wounds where the microcirculation is disrupted. Topical administration of antimicrobials is an attractive approach because it prevents infection and avoids systemic toxicity, while hydrogels are an appealing vehicle for topical drug delivery. They are easy to apply to the wound site by being injectable, the drug release properties can be controlled, and their many characteristics, such as biodegradation, mechanical strength, and chemical and biological response to stimuli can be tailored. Hydrogels also create a moist wound environment that is beneficial for healing. The purpose of this study was to formulate an agarose hydrogel that contains high concentrations of minocycline or gentamicin and study its characteristics. Subsequently, the minocycline agarose hydrogel was tested in a porcine burn model and its effect as a prophylactic treatment was studied. The results demonstrated that 0.5% agarose in water was the optimal concentration in terms of viscosity and pH. Bench testing at room temperature demonstrated that both antibiotics remained stable in the hydrogel for at least 7 days and both antibiotics demonstrated sustained release over the time of the experiment. The porcine burn experiment showed that prophylactic treatment with the agarose minocycline hydrogel decreased the burn depth and reduced the number of bacteria as efficiently as the commonly used silver sulfadiazine cream.

Novel negative pressure wound therapy device without foam or gauze is effective at -50 mmHg.

Negative pressure wound therapy (NPWT) promotes healing in acute or chronic wounds. Conventional NPWT devices consist of a filler (such as foam or gauze) that covers the wound and of a permeable membrane and tubing that connects the space under the membrane to a suction pump. The permeable membrane increases airflow and thus increases the required pump capacity that can cause patient discomfort or even ischemia in wounds with compromised vascularity. In addition, foam or gauze may fragment and become colonized with bacteria over time. To mitigate these, negative aspects, we have developed a new impermeable single layer component membrane dressing to deliver NPWT that does not need a foam or gauze to function. Therefore, the purpose of this study was to introduce this novel NPWT system (platform wound device, PWD) and evaluate its usability and effectiveness in the treatment of porcine full-thickness burns. A total of 48 burn wounds were created across four Yorkshire pigs on the dorsum. Wounds were created on day 0 and continuous NPWT with -50 mmHg and - 80 mmHg was initiated immediately. Subsequently, the burns were debrided on day 3 and animals were euthanized on day 7. The efficacy of the PWD on wound healing and reduction of bacterial burden was measured and compared to wounds that did not receive NPWT. The results showed that PWD promoted wound healing by outperforming the wounds that did not receive NPWT and that PWD was efficient at reducing bacteria from the burn eschar and from the wound bed. In conclusion, this study demonstrated that PWD promoted wound healing with a negative pressure as low as -50 mmHg, which likely benefits healing and avoids potential safety issues.

PWD: Treatment Platform for Both Prolonged Field Care and Definitive Treatment of Burn-Injured Warfighters.

INTRODUCTION: Burns are a very frequent injury type in the battlefield, comprising 5-20% of combat casualties in the recent conflicts. Almost 80% of the burns occur to the face, in part because the face is often not protected. Immediate treatment is critical in the first hours after severe burn injury in order to prevent infection and wound progression. Immediate treatment in the battlefield can be a serious challenge especially if the injury occurs in a remote area with limited transport options. Therefore, novel treatment modalities for prolonged field care when transport to the definitive care is delayed are needed. The purpose of this study was to utilize the platform wound device (PWD) with negative pressure capabilities for the immediate and definitive treatment of porcine full-thickness head burns. MATERIALS AND METHODS: Full-thickness burn wounds were created on foreheads of seven Yorkshire pigs. Burns were created on day 0, immediately enclosed with the PWD and treated topically with minocycline and lidocaine. On day 3, the burns were surgically debrided. Subsequently, new PWDs were placed on the wounds and continuous negative pressure wound therapy was initiated with either -50 mmHg or -80 mmHg. On day 7, the animals were euthanized and wounds were harvested for analyses. Control wounds were treated with silver sulfadiazine cream. RESULTS: The PWD treatment with negative pressure significantly reduced erythema and edema in the injured tissue and promoted granulation tissue and neocollagen formation by day 7 in comparison to control wounds. In addition, the PWD with both topical minocycline and negative pressure (-80 mmHg or -50 mmHg) reduced bacterial counts in the wounds similar to the current standard of care. CONCLUSION: This study demonstrates that the PWD is an effective platform for delivery of antibiotics and negative pressure wound therapy for the treatment of full-thickness burns. Therefore, the PWD may be utilized for both prolonged field care and definitive treatment of burn- and blast-injured warfighters.

Topically Delivered Minocycline Penetrates a Full-Thickness Burn Eschar and Reduces Tissue Bacterial Counts.

Injuries to the skin are often complicated by invasive infections. Standard treatment with intravenous antibiotics has limited tissue penetration and sometimes, major systemic toxicity. Traditional topical delivery of antimicrobials also has limited effectiveness and duration of action. We demonstrate the use of a new Platform Wound Device (PWD) for delivery of topical, ultrahigh concentrations of minocycline as well as lidocaine onto the burn eschar and on the surface of excisional wounds in a total of 56 burn wounds and 24 excisional wounds in a porcine model. Wounds were created on day 0, debrided on day 3, and pigs were killed on day 7. After 3 days of PWD with minocycline treatment, bacterial count was 5.44 log CFU/g in dorsal wound tissue inoculated with methicillin-resistant Staphylococcus aureus, less than that after treatment with silver sulfadiazine cream (7.64 log CFU/g). Pain was also relieved or eliminated in burn wounds and full-thickness excisional wounds when lidocaine was delivered by the PWD. The results demonstrate that ultrahigh concentrations of antibiotics can be delivered effectively by the PWD, and will accelerate wound bed preparation.