Showing papers in "Advances in wound care in 2017"
TL;DR: Hyperbaric oxygen therapy has been shown to significantly improve healing rates in certain problem wounds, including advanced diabetic foot ulcers and late effect radiation injury, and is provided in a variety of clinical settings by providers with varying levels of expertise.
Abstract: Significance: Hyperbaric oxygen therapy (HBOT) is an important advanced therapy in the treatment of problem wounds, including diabetic foot ulcers and late effect radiation injury. HBOT remains among the safest therapies used today. Nonetheless, there are side effects associated with HBOT. It is important for providers to be able to identify, understand, and quantify these side effects for prevention, management, and informed consent. Recent Advances: The past two decades have seen significant advancements in our understanding of the underlying mechanisms of HBOT. This has led to a better understanding of the underlying reason for clinical benefit. It has also led to a better understanding of its side effects. Moreover, more recent literature allows for better quantification of these side effects. This review will highlight these side effects. Critical Issues: Wound healing in the case of problem nonhealing wounds requires the use of various advanced treatment modalities, including HBOT. HBOT has been sho...
166 citations
TL;DR: The development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.
Abstract: Significance: Excessive scarring is major clinical and financial burden in the United States. Improved therapies are necessary to reduce scarring, especially in patients affected by hypertrophic and keloid scars. Recent Advances: Advances in our understanding of mechanical forces in the wound environment enable us to target mechanical forces to minimize scar formation. Fetal wounds experience much lower resting stress when compared with adult wounds, and they heal without scars. Therapies that modulate mechanical forces in the wound environment are able to reduce scar size. Critical Issues: Increased mechanical stresses in the wound environment induce hypertrophic scarring via activation of mechanotransduction pathways. Mechanical stimulation modulates integrin, Wingless-type, protein kinase B, and focal adhesion kinase, resulting in cell proliferation and, ultimately, fibrosis. Therefore, the development of therapies that reduce mechanical forces in the wound environment would decrease the risk of developing excessive scars. Future Directions: The development of novel mechanotherapies is necessary to minimize scar formation and advance adult wound healing toward the scarless ideal. Mechanotransduction pathways are potential targets to reduce excessive scar formation, and thus, continued studies on therapies that utilize mechanical offloading and mechanomodulation are needed.
132 citations
TL;DR: TMR has the potential to treat pain from neuromas while enabling amputee patients to return to their activities of daily living and improve prosthetic use and tolerance and demonstrates great potential for establishing a new standard of care for amputees.
Abstract: Scope and Significance: There are ∼185,000 amputations each year and nearly 2 million amputees currently living in the United States. Approximately 25% of these amputees will experience chronic pain issues secondary to localized neuroma pain and/or phantom limb pain. Problem: The significant discomfort caused by neuroma and phantom limb pain interferes with prosthesis wear, subjecting amputees to the additional physical and psychological morbidity associated with chronic immobility. Although numerous neuroma treatments are described, none of these methods are consistently effective in eliminating symptoms. Translational Relevance: Targeted muscle reinnervation (TMR) is a surgical technique involving the transfer of residual peripheral nerves to redundant target muscle motor nerves, restoring physiological continuity and encouraging organized nerve regeneration to decrease and potentially prevent the chaotic and misdirected nerve growth, which can contribute to pain experienced within the residual limb. Clinical Relevance: TMR represents one of the more promising treatments for neuroma pain. Prior research into "secondary" TMR performed in a delayed manner after amputation has shown great improvement in treating amputee pain issues because of peripheral nerve dysfunction. "Primary" TMR performed at the time of amputation suggests that it may prevent neuroma formation while avoiding the risks associated with a delayed procedure. In addition, TMR permits the target muscles to act as bioamplifiers to direct bioprosthetic control and function. Summary: TMR has the potential to treat pain from neuromas while enabling amputee patients to return to their activities of daily living and improve prosthetic use and tolerance. Recent research in the areas of secondary (i.e., delayed) and primary TMR aims to optimize efficacy and efficiency and demonstrates great potential for establishing a new standard of care for amputees.
92 citations
TL;DR: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinicians to maintain the translational efficacy of this approach.
Abstract: Significance: With an aging population leading to an increase in diabetes and associated cutaneous wounds, there is a pressing clinical need to improve wound-healing therapies. Recent Advances: Tissue engineering approaches for wound healing and skin regeneration have been developed over the past few decades. A review of current literature has identified common themes and strategies that are proving successful within the field: The delivery of cells, mainly mesenchymal stem cells, within scaffolds of the native matrix is one such strategy. We overview these approaches and give insights into mechanisms that aid wound healing in different clinical scenarios. Critical Issues: We discuss the importance of the biomimetic niche, and how recapitulating elements of the native microenvironment of cells can help direct cell behavior and fate. Future Directions: It is crucial that during the continued development of tissue engineering in wound repair, there is close collaboration between tissue engineers and clinici...
89 citations
TL;DR: This is the first study to characterize components that function in wound healing, including inhibitor and protease content and activity, in micronized dHACM, providing a better understanding of how micronization dH ACM tissue can be used to effectively promote wound repair.
Abstract: Objective: The use of bioactive extracellular matrix (ECM) grafts such as amniotic membranes is an attractive treatment option for enhancing wound repair. In this study, the concentrations, activity, and distribution of matrix components, growth factors, proteases, and inhibitors were evaluated in PURION® Processed, micronized, dehydrated human amnion/chorion membrane (dHACM; MiMedx Group, Inc.). Approach: ECM components in dHACM tissue were assessed by using immunohistochemical staining, and growth factors, cytokines, proteases, and inhibitors were quantified by using single and multiplex ELISAs. The activities of proteases that were native to the tissue were determined via gelatin zymography and EnzChek® activity assay. Results: dHACM tissue contained the ECM components collagens I and IV, hyaluronic acid, heparin sulfate proteoglycans, fibronectin, and laminin. In addition, numerous growth factors, cytokines, chemokines, proteases, and protease inhibitors that are known to play a role in the wound-heal...
74 citations
TL;DR: Real-world data from the U.S. Wound Registry is compared with randomized controlled trials and publicly reported wound outcomes and criteria for honest reporting of wound outcomes are developed and it is developed that practitioners should report DFU and VLU healing rates in comparison to whether the wound would have healed.
Abstract: Significance: We compare real-world data from the U.S. Wound Registry (USWR) with randomized controlled trials and publicly reported wound outcomes and develop criteria for honest reporting of wound outcomes, a requirement of the new Quality Payment Program (QPP). Recent Advances: Because no method has existed by which wounds could be stratified according to their likelihood of healing among real-world patients, practitioners have reported fantastically high healing rates. The USWR has developed several risk-stratified wound healing quality measures for diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) as part of its Qualified Clinical Data Registry (QCDR). This allows practitioners to report DFU and VLU healing rates in comparison to the likelihood of whether the wound would have healed. Critical Issues: Under the new QPP, practitioners must report at least one practice-relevant outcome measure, and it must be risk adjusted so that clinicians caring for the sickest patients do not appear to have w...
73 citations
TL;DR: This work has revealed the diverse and dynamic bacterial communities that colonize chronic wounds, and examined fungal colonization and interactions with the bacterial component of the microbiome, their relationship with the host, and influence on wound outcomes.
Abstract: Significance: Culture-independent methods have revealed the diverse and dynamic bacterial communities that colonize chronic wounds. Only recently have studies begun to examine fungal colonization and interactions with the bacterial component of the microbiome, their relationship with the host, and influence on wound outcomes. Recent Advances: Studies using culture-independent sequencing methods reveal that fungi often go undetected in wounds. Candida spp. and Cladosporidium spp. are the most commonly identified fungi in wounds. The wound environment may promote multispecies biofilm formation between bacteria and fungi in wounds, with implications for pathogenicity, treatment, and outcomes. Critical Issues: Identifying microorganisms that are problematic for healing will require a comprehensive understanding of all members of the polymicrobial wound community, including fungi and bacteria. Improved reference databases and bioinformatics tools for studying fungal communities will stimulate further research ...
65 citations
TL;DR: Evidence now shows that multiple types of cells, including infiltrating or resident inflammatory cells, keratinocytes, fibroblasts, and ECs, express specific types of Toll-like receptors, which sheds new light on the mechanism by which the inflammatory or innate immune response is initiated in wound healing.
Abstract: Significance: Inflammation is an integral part of immune response and supports optimal wound healing in adults Inflammatory cells such as neutrophils, macrophages, dendritic cells, lymphocytes, and mast cells produce important cytokines, chemokines, and growth factors These immune cells interact with keratinocytes, fibroblasts, and endothelial cells (ECs), as well as the extracellular matrix within a complicated network that promotes and regulates wound healing Aberrant and persistent inflammation may result in delayed wound healing, scar formation, or chronic wounds Targeting the molecules involved in the inflammatory response may have great potential therapeutic value Recent Advances and Critical Issues: Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns from microbes or danger-associated molecular patterns from damaged cells The discovery of TLRs sheds new light on the mechanism by which the inflammatory or innate immune response is initiated in wound healing Convincing evidence now shows that multiple types of cells, including infiltrating or resident inflammatory cells, keratinocytes, fibroblasts, and ECs, express specific types of TLRs Experimental reduction of certain TLRs or treatment of wounds with TLR ligands has been shown to affect wound healing A better understanding of the involvement of TLRs in the innate immune response during skin wound healing may suggest novel strategies to improve the quality of tissue repair Future Directions: Despite the indisputable role of TLRs in regulating the immune response in acute wound healing, the functions of TLRs that are relevant to human wound healing and chronic wounds are poorly understood
62 citations
TL;DR: Hyperbaric oxygen (HBO) has demonstrated utility in the salvage of compromised grafts/flaps and Mechanisms underlying these beneficial effects include increased oxygenation, improved fibroblast function, neovascularization, and amelioration of IR injury.
Abstract: Significance: Tissue grafts and flaps are used to reconstruct wounds from trauma, chronic disease, tumor extirpation, burns, and infection. Despite careful surgical planning and execution, reconstructive failure can occur due to poor wound beds, radiation, random flap necrosis, vascular insufficiency, or ischemia-reperfusion (IR). Traumatic avulsions and amputated composite tissues-compromised tissue-may fail from crush injury and excessively large sizes. While never intended, these complications result in tissue loss, additional surgery, accrued costs, and negative psychosocial patient effects. Recent Advances: Hyperbaric oxygen (HBO) has demonstrated utility in the salvage of compromised grafts/flaps. It can increase the likelihood and effective size of composite graft survival, improve skin graft outcomes, and enhance flap survival. Mechanisms underlying these beneficial effects include increased oxygenation, improved fibroblast function, neovascularization, and amelioration of IR injury. Critical Issues: Common strategies for the compromised graft or flap include local wound care, surgical debridement, and repeated reconstruction. These modalities are associated with added costs, time, need for reoperation, morbidity, and psychosocial effects. Preservation of the amputated/avulsed tissues minimizes morbidity and maximizes the reconstructive outcome by salvaging the compromised tissue and obviating additional surgery. HBO is often overlooked as a potential tool that can limit these issues. Future Directions: Animal studies demonstrate a benefit of HBO in the treatment of compromised tissues. Clinical studies support these findings, but are limited to case reports and series. Further research is needed to provide multicenter prospective clinical studies and cost analyses comparing HBO to other adjunctive therapies in the treatment of compromised grafts/flaps.
59 citations
TL;DR: This review provides current overview of the emerging role of innate immunity in driving fibrosis, and preventing its resolution, in scleroderma (systemic sclerosis, SSc).
Abstract: Significance: This review provides current overview of the emerging role of innate immunity in driving fibrosis, and preventing its resolution, in scleroderma (systemic sclerosis, SSc). Understanding the mechanisms of dysregulated innate immunity in fibrosis and SSc will provide opportunities for therapeutic interventions using novel agents and repurposed existing drugs. Recent Advances: New insights from genomic and genetic studies implicate components of innate immune signaling such as pattern recognition receptors (PRRs), downstream signaling intermediates, and endogenous inhibitors, in fibrosis in SSc. Recent studies distinguish innate immune signaling in tissue-resident myofibroblasts and bone marrow–derived immune cells and define their roles in the development and persistence of tissue fibrosis. Critical Issues: Activation of toll-like receptors (TLRs) and other PRR mechanisms occurs in resident nonimmune cells within injured tissue microenvironments. These cells respond to damage-associated molecu...
53 citations
TL;DR: This review will comprehensively discuss the current clinical practices used on patients with cutaneous wounds, including both traditional skin grafting procedures and advanced grafting techniques with cultured skin stem cells.
Abstract: Significance: Skin serves as a protective barrier for mammals. Epidermal stem cells are responsible for maintaining skin homeostasis. When cutaneous injuries occur, skin homeostasis and integrity are damaged, leading to dire consequences such as acute, chronic, or infected wounds. Skin wound healing is an intrinsic self-saving chain reaction, which is crucial to facilitating the replacement of damaged or lost tissue. Recent Advances: An immense amount of research has uncovered the underlying mechanisms behind the complex and highly regulated wound healing process. In this review, we will dissect the biological process of adult skin wound healing and emphasize the importance of epidermal stem cells during the wound healing. Critical Issues: We will comprehensively discuss the current clinical practices used on patients with cutaneous wounds, including both traditional skin grafting procedures and advanced grafting techniques with cultured skin stem cells. The majority of these leading techniques still retain some deficiencies during clinical use. Moreover, the regeneration of skin appendages after severe injuries remains a challenge in treatment. Future Directions: Understanding epidermal stem cells and their essential functions during skin wound healing are fundamental components behind the development of clinical treatment on patients with cutaneous wounds. It is important to improve the current standard of care and to develop novel techniques improving patient outcomes and long-term rehabilitation, which should be the goals of future endeavors in the field of skin wound healing.
TL;DR: A class of short non-coding RNAs, microRNAs, has been found to be indispensable for all the phases of skin wound healing and plays important role in regulating cellular physiology and pathology.
Abstract: Significance: Wound healing is a basic physiological process that is utilized to keep the integrity of the skin. Impaired wound repair, such as chronic wounds and pathological scars, presents a major health and economic burden worldwide. To date, efficient targeted treatment for these wound disorders is still lacking, which is largely due to our limited understanding of the biological mechanisms underlying these diseases. Research driven around discovering new therapies for these complications is, therefore, an urgent need. Recent Advances: The vast majority of the human genome is transcribed to RNAs that lack protein-coding capacity. Intensive research in the recent decade has revealed that these non-coding RNAs (ncRNAs) function as important regulators of cellular physiology and pathology, which makes them promising therapeutic and diagnostic entities. Critical Issues: A class of short ncRNAs, microRNAs, has been found to be indispensable for all the phases of skin wound healing and plays important role...
TL;DR: Knowledge of DAMP- and PAMP-TLR signaling may lead to treatments that ameliorate local and systemic inflammation and reduce scarring and other burn injury sequela, and TLR-pathway-targeting treatments applied at different times postburn injury might improve scarring.
Abstract: Significance: Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) emanate from burn-injured tissue and enter systemic circulation. Locally and systemically, they activate pattern-recognition receptors, including toll-like receptors (TLRs), to stimulate cytokine secretion, which in the severest burns typically results in extreme systemic cytokine levels, a dysfunctioning immune system, infection, impaired healing, and excessive scarring. This system-wide disruption of homeostasis can advance to life-threatening, multiorgan dysfunction syndrome. Knowledge of DAMP- and PAMP-TLR signaling may lead to treatments that ameliorate local and systemic inflammation and reduce scarring and other burn injury sequela. Recent Advances: Many PAMPs and DAMPs, the TLRs they activate, and their downstream signaling molecules have been shown to contribute to local and systemic inflammation and tissue damage following burn injury. Critical Issues: Whether TLR-pathway-targeting treatments applied at different times postburn injury might improve scarring remains an open question. The evaluation of this question requires the use of appropriate preclinical and clinical burn models carried out until after mature scar has formed. Future Directions: After TLR-pathway-targeting treatments are evaluated in porcine burn wound models and their safety is demonstrated, they can be tested in proof-of-concept clinical burn wound models.
TL;DR: Engineered, vascularized tissues as well as angiogenic growth factor-releasing hydrogels could replace defective tissues and the development of novel vascularization-promoting or -inhibiting therapeutics will benefit from physiologically relevant vessel models.
Abstract: Significance: Diseases related to vascular malfunction, hyper-vascularization, or lack of vascularization are among the leading causes of morbidity and mortality. Engineered, vascularized tissues as well as angiogenic growth factor-releasing hydrogels could replace defective tissues. Further, treatments and testing of novel vascular therapeutics will benefit significantly from models that allow for the study of vascularized tissues under physiological relevant in vitro conditions. Recent Advances: Inspired by fibrin, the provisional matrix during wound healing, naturally derived and synthetic hydrogel scaffolds have been developed for vascular engineering. Today, engineers and biologists use commercially available hydrogels to pre-vascularize tissues, to control the delivery of angiogenic growth factors, and to establish vascular diseases models. Critical Issue: For clinical translation, pre-vascularized tissue constructs must be sufficiently large and stable to substitute function-relevant tissue defects...
TL;DR: Clinical research into the use of topical antiseptics in wound care would lower the risk of furthering antibiotic resistance and contribute to more effective antibiotic use, and experimental and surveillance data are needed on the resistance and tolerance patterns associated with topical antisesptic use in wound infections.
Abstract: Scope and Significance: The topical use of antiseptics for wound care has a role in an antimicrobial stewardship strategy. However, the details of this role need clarification. Further clinical research into the use of topical antiseptics in wound care would lower the risk of furthering antibiotic resistance and contribute to more effective antibiotic use. As part of this research, experimental and surveillance data are needed on the resistance and tolerance patterns associated with topical antiseptic use in wound infections. Objective: The development of antibiotic resistance presents global challenges in terms of patient harm and increased healthcare costs. The treatment of “at risk” and infected wounds contributes to this conundrum. Synergies between antibiotics and antiseptics and their appropriate combined use need exploration. Approach: A review of available evidence on the appropriateness of antiseptics as a fundamental component of antimicrobial stewardship strategies has been undertaken. Innovati...
TL;DR: It is demonstrated that this portable handheld electrospinning device can be utilized for different formulations and materials and customized according to the characteristics of the target wound at the various stages of wound healing.
Abstract: Objectives: The aim of this study was to determine the feasibility of a portable electrospinning device for the application of wound dressings. Approach: Four polymer nanofibers dressings were applied on superficial partial thickness wounds to a porcine model and compared with a traditional paraffin tulle gras dressing. The polymer nanofibrous dressings were applied using a handheld portable electrospinning device activated at a short distance from the wound. The partial thickness donor sites were evaluated on day 2, 7, and 14 when dressings were removed and tissue samples were taken for histological examination. Results: No significant difference was detected between the different electrospun nanofibrous dressings and traditional paraffin tulle gras. Desirable characteristics of the electrospun nanofiber dressing group included nontouch technique, ease of application, adherence and reduction in wound edema and inflammation. There was no delayed wound healing or signs of infection reported in both the electrospun nanofiber and traditional tulle gras dressings. Innovation: Used on partial thickness wounds, polymer electrospun nanofiber dressings provide excellent surface topography and are a nontouch, feasible, and safe method to promote wound healing with the potential to reduce wound infections. Such custom-made nanofibrous dressings have implications for the reduction of pain and trauma, number of dressing changes, scarring, and an added cost benefit. Conclusion: We have demonstrated that this portable handheld electrospinning device can be utilized for different formulations and materials and customized according to the characteristics of the target wound at the various stages of wound healing.
TL;DR: Treatment outcomes at this institution's management protocol of Fournier's gangrene are comparable to those reported in recent literature, a significant decline from the historical MR of 50-60%.
Abstract: Objective: The outcome of Fournier's gangrene (FG) may be affected by comorbidities, demographics, and choice of treatment modality. We sought to evaluate our institution's management protocol of FG measured by mortality rate (MR) and length of hospital stay (LHS) in a retrospective cohort study. Approach: A database of 20 FG cases at our institution throughout the 2009–2016 study period was assembled by a retrospective review of medical records. A Fournier's Gangrene Severity Index Score (FGSIS) was calculated for each case. Data were analyzed for statistical significance using logistic regression. Results: The most common presentation of FG at our institution was a hyperglycemic diabetic male in his fifth decade of life with a second risk factor such as recent surgery or active malignancy. The average FGSIS was 9 overall and 14 for the mortalities. An increased FGSIS was predictive of having an increased MR or hospital stay above the median (>25 days) (p = 0.0194). The average LHS was 32 days overall, 2...
TL;DR: Despite recent advancements in prosthetic and orthotic devices, altered movement and mechanical loading patterns have been identified among persons with LL and salvage, which are purported risk factors for the development of longer term secondary musculoskeletal conditions and may limit fun...
Abstract: Significance: Advances in field-based trauma care, surgical techniques, and protective equipment have collectively facilitated the survival of a historically large number of service members (SMs) following combat trauma, although many sustained significant composite tissue injuries to the extremities, including limb loss (LL) and limb salvage (LS). Beyond the acute surgical and rehabilitative efforts that focus primarily on wound care and restoring mobility, traumatic LL and LS are associated with several debilitating longer term secondary health conditions (e.g., low back pain [LBP], osteoarthritis [OA], and cardiovascular disease [CVD]) that can adversely impact physical function and quality of life. Recent Advances: Despite recent advancements in prosthetic and orthotic devices, altered movement and mechanical loading patterns have been identified among persons with LL and salvage, which are purported risk factors for the development of longer term secondary musculoskeletal conditions and may limit functional outcomes and/or concomitantly impact cardiovascular health. Critical Issues: The increased prevalence of and risk for LBP, OA, and CVD among the relatively young cohort of SMs with LL and LS significantly impact physiological and psychological well-being, particularly over the next several decades of their lives. Future Directions: Longitudinal studies are needed to characterize the onset, progression, and recurrence of health conditions secondary to LL and salvage. While not a focus of the current review, detailed characterization of physiological biomarkers throughout the rehabilitation process may provide additional insight into the current understanding of disease processes of the musculoskeletal and cardiovascular systems.
TL;DR: Blockade of the opioid growth factor-OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.
Abstract: Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex® was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synt...
TL;DR: The development of novel TLR ligand-, pathway-, and/or target gene-specific therapeutics may have clinical utility in the management of the exuberant inflammatory/fibrotic tissue response to injury without compromising the host defense to pathogens.
Abstract: Significance: Chronic inflammation and maladaptive repair contribute to the development of fibrosis that negatively impacts quality of life and organ function. The toll-like receptor (TLR) system is a critical node in the tissue response to both exogenous (pathogen-associated) and endogenous (damage-associated) molecular pattern factors (PAMPs and DAMPs, respectively). The development of novel TLR ligand-, pathway-, and/or target gene-specific therapeutics may have clinical utility in the management of the exuberant inflammatory/fibrotic tissue response to injury without compromising the host defense to pathogens. Recent Advances: DAMP ligands, released upon wounding, and microbial-derived PAMPs interact with several TLRs, and their various coreceptor partners, engaging downstream pathways that include Src family kinases, the epidermal growth factor receptor, integrins and the tumor suppressor phosphatase and tensin homolog (PTEN). Toll-like receptor 4 (TLR4) activation enhances cellular responses to the ...
TL;DR: Topical oxygen devices are cleared for the following indications for use of various etiologies: skin ulcerations due to diabetes, venous stasis, postsurgical infections and gangrenous lesions, decubitus ulcers; amputations/infected stumps; skin grafts; burns; and frostbite.
Abstract: Objective: Topical oxygen devices are Food and Drug Administration (FDA) cleared for the following indications for use of various etiologies: skin ulcerations due to diabetes, venous stasis, postsurgical infections and gangrenous lesions, decubitus ulcers; amputations/infected stumps; skin grafts; burns; and frostbite. The goal of this study was to understand the impact of topical oxygen therapy (TOT) on patient outcomes, including amputation and healing rates. Approach: This retrospective chart review included records collected between January 1, 2007, and July 18, 2016, from male and female patients ranging in age from 4 years to 105 years. All wounds were at least 1 cm2 and were treated with at least one separate modality before treatment with TOT and then treated with TOT for a minimum of 2 weeks in compliance with the FDA-approved indications. All records were from wounds that were no longer being treated with TOT. Results: In this study, TOT was associated with an overall rate of 59.4% for a reducti...
TL;DR: VEGFR-2 stimulation can enhance the quality of skin repair, at least, in part, through the induction of IL-10 expression and dampening of wound inflammation and fibrosis, as well as to treat impaired healing or to prevent excess scarring.
Abstract: Objective: Vascular endothelial growth factor (VEGF) family members are critical regulators of tissue repair and depending on their distinct pattern of receptor specificity can also promote inflammation and scarring. This study utilized a receptor-selective VEGF to examine the role of VEGF receptor (VEGFR)-2 in scar tissue (ST) formation. Approach: Cutaneous skin wounds were created in mice using a 4 mm biopsy punch and then treated until closure with purified VEGF-E derived from orf virus stain NZ-2. Tissue samples were harvested to measure gene expression using quantitative PCR and to observe ST formation through histological examination and changes in cell populations by immunofluorescence. Results: VEGFR-2-activation with VEGF-E increased expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced macrophage infiltration and myofibroblast differentiation in wounded skin compared with controls. VEGF-E treatment also increased microvascular density and improved pericyte coverage of blood ve...
TL;DR: In this paper, the authors compared three regimens and established superiority in terms of objective and subjective outcomes, and concluded that a combination of triamcinolone acetonide (TAC), 5-fluorouracil (5FU), and a combination in Group T + F every 3 weeks till 24 weeks or till the keloid resolved.
Abstract: Objective: Despite the myriad options available, there is no universally accepted treatment for keloids. Our objective was to compare three regimens and establish superiority in terms of objective and subjective outcomes. Approach: In this randomized parallel group study, 60 patients were enrolled and randomly allocated to three groups. Patients received intralesional injections of triamcinolone acetonide (TAC) in Group TAC, 5-fluorouracil (5FU) in Group 5FU, and a combination in Group T + F every 3 weeks till 24 weeks or till the keloid resolved. Results: There was a reduction in all parameters at every successive assessment in all three groups. Improvement in terms of height, vascularity, and pliability was fastest with 5FU, TAC, and T + F group, respectively, which was statistically significant. Decrease in pigmentation was significantly faster with T+F. Reduction in pruritus, however, was significantly faster with 5FU than the other groups, but the difference in reduction of pain among the three groups was not significant. Telangiectasias and skin atrophy were seen most commonly in TAC group, while skin ulceration was a common problem in 5FU group. Conclusion: TAC, 5FU, and their combination are all effective in keloid scars. A combination of TAC +5FU seems to offer the balanced benefit of faster and more efficacious response with lesser adverse effects when compared to individual drugs.
TL;DR: SDF1-ELP is a promising agent for the treatment of chronic skin wounds because it promotes the migration of cells and induces vascularization similar to SDF1 in vitro and is more stable in wound fluids compared to S DF1.
Abstract: Objective: In previous work, we demonstrated the development of a novel fusion protein containing stromal cell-derived growth factor-1 alpha juxtaposed to an elastin-like peptide (SDF1-ELP), which has similar bioactivity, but is more stable in elastase than SDF1. Herein, we compare the ability of a single topical application of SDF1-ELP to that of SDF1 in healing 1 × 1 cm excisional wounds in diabetic mice. Approach: Human Leukemia-60 cells were used to demonstrate the chemotactic potential of SDF1-ELP versus SDF1 in vitro. Human umbilical vascular endothelial cells were used to demonstrate the angiogenic potential of SDF1-ELP versus SDF1 in vitro. The bioactivity of SDF1-ELP versus SDF1 after incubation in ex-vivo diabetic wound fluid was compared. The in-vivo effectiveness of SDF1-ELP versus SDF1 was compared in diabetic mice wound model by monitoring for the number of CD31+ cells in harvested wound tissues. Results: SDF1-ELP promotes the migration of cells and induces vascularization similar to SDF1 in...
TL;DR: Evidence is provided that the use of elevated vacuum pressure data may provide a method for prosthetists to quantify and monitor socket fit, and the relationship betweensocket fit, limb motion, and limb health is investigated to define optimal socket fit parameters.
Abstract: Objective: Prosthetic sockets are custom made for each amputee, yet there are no quantitative tools to determine the appropriateness of socket fit. Ensuring a proper socket fit can have significant effects on the health of residual limb soft tissues and overall function and acceptance of the prosthetic limb. Previous work found that elevated vacuum pressure data can detect movement between the residual limb and the prosthetic socket; however, the correlation between the two was specific to each user. The overall objective of this work is to determine the relationship between elevated vacuum pressure deviations and prosthetic socket fit. Approach: A tension compression machine was used to apply repeated controlled forces onto a residual limb model with sockets of different internal volume. Results: The vacuum pressure-displacement relationship was dependent on socket fit. The vacuum pressure data were sensitive enough to detect differences of 1.5% global volume and can likely detect differences even smaller. Limb motion was reduced as surface area of contact between the limb model and socket was maximized. Innovation: The results suggest that elevated vacuum pressure data provide information to quantify socket fit. Conclusions: This study provides evidence that the use of elevated vacuum pressure data may provide a method for prosthetists to quantify and monitor socket fit. Future studies should investigate the relationship between socket fit, limb motion, and limb health to define optimal socket fit parameters.
TL;DR: In this paper, Xanthine oxidoreductase (XOR), a molybdoflavin enzyme, is shown to be an important source of reactive oxygen species (ROS) in various pathologies, including diabetes and chronic wounds.
Abstract: Significance: Chronic wounds are a major burden to patients and to healthcare systems worldwide. These wounds are difficult to heal and treatment is often lengthy and expensive. This has led to research efforts focussed on the wound environment attempting to understand the underlying pathological mechanisms of impaired wound healing. While some of this research has translated to advancements in wound therapies and implementation of new treatment options, chronic wounds remain a significant challenge to treat. Thus, identification of effective, low-cost, advanced wound therapies that enhance healing rates of these problematic wounds is still essential. Recent Advances and Critical Issues: Xanthine oxidoreductase (XOR), a molybdoflavin enzyme, is emerging as an important source of reactive oxygen species (ROS) in various pathologies, including diabetes and chronic wounds. XOR has recently been shown to be upregulated in chronic wounds, stimulating the overproduction of ROS during dysfunctional wound healing. XOR-induced ROS can amplify and potentiate inflammation in the wound environment further delaying wound closure. Future Directions: The detrimental role of XOR in impaired healing indicates it may be a therapeutic target. Targeted inhibition of XOR has been shown to reduce the expression and activity of this enzyme in diabetic wound models. In turn, this resulted in a significant decrease in ROS levels in the wound environment and improved wound healing. Therefore, repurposing existing XOR inhibitors that are approved for human use may be able to restore homeostasis at the wound site and enable damaged tissue to return to normal healing.
TL;DR: The use of incisional negative-pressure wound therapy (iNPWT) is known to reduce wound infections for several surgical indications and the potential of a new portable negative- pressure therapy device on perineal wound healing in patients undergoing APR was investigated.
Abstract: Objective: Abdominoperineal resection (APR) is associated with high incidence of surgical wound infections. The use of incisional negative-pressure wound therapy (iNPWT) is known to reduce wound infections for several surgical indications. The aim of this pilot study was to investigate the potential of a new portable negative-pressure therapy device on perineal wound healing in patients undergoing APR. Approach: A new single-use incisional negative-pressure therapy device was applied in 10 patients. A negative pressure of -80 mmHg was continued for 7 days postsurgery. Incidence of wound complications and time to wound healing were compared with a historical control group of 10 patients undergoing APR in 2014, treated with conventional wound care. Results: Patient characteristics were comparable in both groups. Mean 1.6 dressings were used per patient. A wound complication was diagnosed in seven patients versus six in the control group. Wound infections were diagnosed median 11.5 days after surgery, compared with 10.5 days in the control group. Duration of wound healing was shorter in the study group (median 8.5 weeks vs. 13 weeks). Innovation: This is the first study to report on the use of this iNPWT device for patients who underwent APR for rectal cancer. Conclusion: In this study, iNPWT did not reduce wound complications. Wound infections occurred slightly later and seemed to have a less severe clinical course. After treatment with iNPWT, the duration of wound healing was shorter.
TL;DR: Rapid recruitment and activation of macrophages may accelerate wound healing and safety and efficacy of α-gal nanoparticles in accelerating wound and burn healing in healthy individuals and in patients with impaired wound healing such as diabetic patients and elderly individuals.
Abstract: Significance: Rapid recruitment and activation of macrophages may accelerate wound healing. Such accelerated healing was observed in wounds and burns of experimental animals treated with α-gal nanoparticles. Recent Advances: α-Gal nanoparticles present multiple α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R). α-Gal nanoparticles applied to wounds bind anti-Gal (the most abundant antibody in humans) and generate chemotactic complement peptides, which rapidly recruit macrophages. Fc/Fc receptor interaction between anti-Gal coating the α-gal nanoparticles and recruited macrophages activates macrophages to produce cytokines that accelerate healing. α-Gal nanoparticles applied to burns and wounds in mice and pigs producing anti-Gal, decreased healing time by 40-60%. In mice, this accelerated healing avoided scar formation. α-Gal nanoparticle-treated wounds, in diabetic mice producing anti-Gal, healed within 12 days, whereas saline-treated wounds became chronic wounds. α-Gal nanoparticles are stable for years and may be applied dried, in suspension, aerosol, ointments, or within biodegradable materials. Critical Issues: α-Gal nanoparticle therapy can be evaluated only in mammalian models producing anti-Gal, including α1,3-galactosyltransferase knockout mice and pigs or Old World primates. Traditional experimental animal models synthesize α-gal epitopes and lack anti-Gal. Future Directions: Since anti-Gal is naturally produced in all humans, it is of interest to determine safety and efficacy of α-gal nanoparticles in accelerating wound and burn healing in healthy individuals and in patients with impaired wound healing such as diabetic patients and elderly individuals. In addition, efficacy of α-gal nanoparticle therapy should be studied in healing and regeneration of internal injuries such as surgical incisions, ischemic myocardium following myocardial infarction, and injured nerves.
TL;DR: The potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate is discussed.
Abstract: Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and...
TL;DR: All stages of PUstreated with CCO achieved faster rates of granulation and subsequent epithelialization compared to PUs treated with medicinal honey as measured by real-world data collected in the hospital outpatient department care setting.
Abstract: Objective: Compare enzymatic debridement using clostridial collagenase ointment (CCO) with autolytic debridement using medicinal honey in the hospital outpatient setting for treating pressure ulcers (PUs). Approach: Retrospective deidentified electronic health records from 2007–2013 were extracted from the U.S. Wound Registry. Propensity score matching followed by multivariable analyses was used to adjust for selection bias and assess treatment effects comparing CCO-treated versus honey-treated PUs. Key outcomes included 100% granulation and epithelialization at 1 year. Results: Five hundred seventeen CCO-treated PUs (446 patients) were matched to corresponding honey-treated PUs (341 patients). The majority of PUs were stage III (CCO 56%, honey 55%). CCO users had significantly fewer total visits (9.1 vs. 12.6; p < 0.001), fewer total selective sharp debridements (2.7 vs. 4.4; p < 0.001), and fewer PUs receiving negative pressure wound therapy (29% vs. 38%; p = 0.002) compared with honey. Innovation: CCO-...