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Diabetes mellitus is a chronic disease characterized by increased blood glucose levels, leading to damage of the nerves blood vessels, subsequently manifesting as organ failures, wounds, or ulcerations. Wounds in patients with diabetes are further complicated because of reduced cytokine responses, infection, poor vascularization, and delayed healing process. Surface-functionalized and bioengineered nanoparticles (NPs) have recently gained attention as emerging treatment modalities for wound healing in diabetes. Here, we review emerging therapeutic NPs to treat diabetic wounds and highlight their discrete delivery mechanisms and sites of action. We further critically assess the current challenges of these nanoengineered materials for successful clinical translation and discuss their potential for growth in the clinical marketplace.

Impaired chronic wound healing is a great challenge for modern medicine. This process causes ulceration especially in the course of diseases such as type II diabetes mellitus.This study assesses the concentration of selected matrix metalloproteinases in the example of metalloproteinase 2, 3, 9, 13 in patients with impaired healing of chronic wounds as a complication of type 2 diabetes.Nineteen people took part in the assessment of wound healing in patients with type 2 diabetes. The control group consisted of 21 healthy people. In the blood serum the concentration of MMP-2, MMP-3, MMP-9 and MMP-13 was determined.The concentrations of MMP-2 and MMP-3 in the group of patients with ulcers were significantly higher (61% and 84% accordingly) compared to those in the control group without chronic wounds. No statistically significant differences in MMP-9 and MMP-13 concentrations were observed between the study and control groups.The increase in MMP-2 concentration, which is particularly active in the degradation of type IV collagen, which is the main component of the basal membranes, in patients with type 2 diabetes may impede and delay the healing of chronic wounds and thus contribute to the intensification of vascular complications. In turn, the increase in MMP-3 concentration, which plays a significant role in vascular diseases, in patients with type 2 diabetes may lead to intensification of atherosclerotic changes involving the arteries of the lower extremities and ulceration.

Peripheral arterial disease can involve tissue loss in up to 50% of patients with diabetic foot syndrome (DFS). Consequently, revascularization of narrowed or occluded arteries is one of the most common forms of comprehensive treatment. However, technically successful angioplasty does not always result in the healing of ulcers. The pathomechanism of this phenomenon is still not fully understood, but inadequate angiogenesis in tissue repair may play an essential role. Changes in pro- and anti-angiogenic factors among patients with DFS are not always clear and conclusive. In particular, some studies underline the role of decreased concentration of pro-angiogenic factors and higher levels of anti-angiogenic mediators. Nevertheless, there are still controversial issues, including the paradox of impaired wound healing despite high concentrations of some pro-angiogenic factors, dynamics of their expression during the healing process, and their mutual relationships. Exploring this process among diabetic patients may provide new insight into well-known methods of treatment and show their real benefits and chances for improving outcomes.

While “population aging” is an accomplishment that deserves acclamation, it is in itself a tremendous challenge. Age-related skin changes, impaired wound healing, and concurrent comorbidities are the deadly triad that contribute most to the development of nonhealing chronic wounds in the elderly. This imposes enormous medical, social, and financial burden. With the rising trend in the aging population, this problem is likely to exacerbate unless multidisciplinary, rapt wound care strategies are developed. The last decade was dedicated to understand the basic biology underlying the wound healing process but most in vitro and animal model studies translated poorly to human conditions. Forthcoming, the focus is on the development of diagnostic and therapeutic strategies to improve healing in this vulnerable age group. Further, understanding the complex pathobiology of cellular senescence and wound healing process is required to develop focused therapy for these “problem wounds” in the elderly.

Impaired wound healing is a major concern in diabetic patients due to unregulated chronic hyperglycemia which further may lead to ulcer, gangrene, and its complications. The present study unveils the accelerative effect of aqueous Anthocephalus cadamba leaf extract on wound healing in diabetic rats. Diabetes was induced in 30 Sprague Dawley female rats by using streptozotocin (except control group I) at the dose of 60 mg/kg intraperitoneally. Diabetic rats were randomized in 3 groups viz. diabetic control group (II), diabetes + Kadam plant leaf extract group (III), and diabetes + 5% povidone–iodine solution group (IV). Surgically sterile wound of 1.77 cm2 was created on the dorsal area of anaesthetized rats. The experimental parameters were assessed by hematobiochemical, histopathological, and western blot techniques. The A cadamba extract treatment group (III) (D + KPLE) showed a significant increase in the percentage of wound closure (82%) at day 21 as compared to the diabetic control group (42%), nondiabetic control group (I) (49%), and povidone–iodine treatment group (75%) group (IV). The findings of the present study suggest that the (D + KPLE) group (III) exhibited marked epithelial regeneration, neovascularization, collagen deposition, and fibroblast proliferation along with higher expression of vascular endothelial growth factor as compared to the diabetic control group (II), which was confirmed by histopathological examination and western blot analysis. The present study suggests that the topical application of aqueous A cadamba leaf extract exhibits accelerative wound-healing properties in diabetic rats.

The prevalence of chronic wounds is increasing with the aging population, with 1% to 2% of the worldwide population experiencing leg ulcers and positive patch tests reported in up to 75% of this population. With the introduction of modern dressings and compression therapies, clinicians should be cognizant of the potential risk of contact dermatitis in patients with leg ulcers. Contact dermatitis (both allergic and irritant) to wound products may present as maceration, pain, and overall impaired wound healing. Herein, we review the literature on contact dermatitis to wound-care products.

Pressure ulcers are preventable, yet highly prevalent, chronic wounds that have significant patient morbidity and high healthcare costs. Like other chronic wounds, they are characterized by impaired wound healing due to dysregulated immune processes. This review will highlight key biochemical pathways in the pathogenesis of pressure injury and how this signaling leads to impaired wound healing. This review is the first to comprehensively describe the current literature on microRNA (miRNA, miR) regulation of pressure ulcer pathophysiology.

Due to the microvascular effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), head and neck reconstructive surgeries utilizing free tissue transfers may be profoundly affected by SARS-CoV-2 infection in the immediate postoperative period. Our objective is to describe two adult patients who developed SARS-CoV-2 after undergoing relatively uncomplicated segmental mandibulectomies. In both cases, the patients were initially negative for SARS-CoV-2, underwent relatively uncomplicated segmental mandibulectomies with fibula free flap reconstructions, and were later discharged in stable conditions. Both patients subsequently experienced significant infectious sequelae at the donor and recipient sites with near-total split-thickness skin graft loss in the donor sites in the setting of postoperative SARS-CoV-2 infection. The first patient developed sepsis and gangrenous changes to his fibula donor site requiring four operative debridements and partial amputation with subsequent osteomyelitis of the remaining fibula. The second patient experienced dehiscence of the oral fibula free flap as well as a 22 cm phlegmon at the fibula donor site that required surgical debridement. In consideration of these cases, SARS-CoV-2 infection during the immediate postoperative period of head and neck reconstruction procedures may elevate the risk of major wound complications. Special consideration must be taken when performing free tissue transfers during the COVID-19 pandemic.

The gut–brain–skin axis is important in wound healing. The aim of this study was to investigate the association between experiencing irritable bowel syndrome (IBS) symptoms, perceived immune fitness, and impaired wound healing. N = 1942 Dutch students (mean (SD) age 21.3 (2.1), 83.6% women) completed an online survey. They were allocated to one of four groups: (1) control group (N = 1544), (2) wound infection (WI) group (N = 65), (3) slow healing wounds (SHW) group (N = 236), or (4) a combination group (COMBI), which experienced both WI and SHW (N = 87). Participants rated their perceived immune fitness on a scale ranging from very poor (0) to excellent (10), and the severity of IBS symptoms (constipation, diarrhea, and pain) was assessed with the Birmingham IBS Symptom Questionnaire. Compared to the control group, perceived immune fitness was significantly poorer for the SHW group (p &lt, 0.001) and COMBI group (p &lt, 0.001), but not for the WI group. Compared to the control group, constipation was reported significantly more frequently by the SHW group (p &lt, 0.001) and the WI group (p = 0.012), diarrhea was reported significantly more frequent by the SHW group (p = 0.038) and the COMBI group (p = 0.004), and pain was reported significantly more frequent by the SHW group (p = 0.020) and COMBI group (p = 0.001). Correlations between IBS complaints and perceived immune fitness were statistically significant (p &lt, 0.001), and also a highly significant and negative association was found between the percentage of participants that reported impaired wound healing and perceived immune fitness (r = −0.97, p &lt, 0.001). In conclusion, among participants with self-reported impaired wound healing, IBS complaints were significantly more severe, and accompanied by a significantly reduced perceived immune fitness.

Medication-induced ulcers are generally rare. Although the tyrosine kinase inhibitor imatinib mesylate is frequently prescribed, the occurrence of ulcers related to the medication has not been previously described. Herein, the authors report a case of a patient with impaired wound healing that was attributed to imatinib mesylate treatment. Providers should maintain suspicion for medication-induced ulcers, particularly if treatment for the presumed underlying cause of an ulcer fails.

Significance: Wound healing involves the phasic production of growth factors (GFs) and cytokines to progress an acute wound to a resolved scar. Dysregulation of these proteins contributes to both wound chronicity and excessive scarring. Direct supplementation of GFs and cytokines for treatment of healing and scarring complications has, however, been disappointing. Failings likely relate to an inability to deliver recombinant proteins at physiologically relevant levels to an environment conducive to healing. Recent Advances: Inspired by the extracellular matrix, natural biomaterials have been developed that resemble human skin, and are capable of delivering bioactives. Hybrid biomaterials made using multiple polymers, fabrication methods, and proteins are proving efficacious in animal models of acute and impaired wound healing. Critical Issues: For clinical translation, these delivery systems must be tailored for specific wound indications and the correct phase of healing. GFs and cytokines must be delivered in a controlled manner that will target specific healing or scarring impairments. Preclinical assessment in clinically relevant animal models of impaired or excessive healing is critical. Future Directions: Clinical success will likely depend on the GF or cytokine selected, their compatibility with the chosen biomaterial(s), degradation rate of the fabricated system, and the degree of control over release kinetics. Further testing is essential to assess which wound indications are most suited to specific delivery systems and to prove whether they provide superior efficacy over direct protein therapies.

Impaired wound healing is of the most conspicuous characteristics of diabetic mellitus. Reduced blood flow, chronic inflammatory reactions, infection, endothelial dysfunction, elevated levels of reactive oxygen species, and metabolic disorders cause wounds to heal more slowly in these patients. Previous studies have reported useful impacts of growth factors in management of such wounds. However, due to their short half-life and low stability, a suitable delivery platform with sustained release profile may boost their healing potential. Controlled and localized delivery of growth factors via electrospun fibers have been extensively explored in previous studies. The electrospinning method; although not new, has turned out to be extremely effective for the preparation of delivery carriers for growth factors. Due to their structural resemblance to native tissues' extracellular matrix, high encapsulation efficacy, tunability, and high surface to volume ratio, electrospun scaffolds have gained significant attention in drug delivery and tissue engineering. In the current review, careful integration of current research regarding the applications of growth factors' delivery through electrospun fibers in diabetic wounds healing has been done. This review will not only give an insight into the current updates, but will also highlights the future perspectives and challenges.

Recently, we reported that some wound dressings caused complement activation at the interface of wound dressing and blood. Since complement activation is associated with impaired wound healing, we investigated whether this activation of the complement cascade at the interface of wound dressings and blood does impair reepithelialization in a scratch wound healing assay. Although some samples showed higher levels of the complement activation marker SC5b-9 in our study, reepithelialization of the samples did not significantly differ from the control group. Further studies have to clarify if complement activation at the interface of wound dressings and blood plays a relevant role in the healing process especially in long-time experiments.

ntroduction: Lower limb amputation is a surgery performed as a last resort, when all other therapeutic options have been exhausted. The duration of treatment lasts from a few to several months and depends on the extent of amputation, the patientas overall health and the course of the stump healing process. Materials and methods A retrospective analysis was performed using the database of the General and Vascular Surgery Ward of the Nikolay Pirogov Regional Specialist Hospital in Łodź. Patients who underwent lower limb amputation at the transfemoral level in 2017 were analyzed. 92 patients undergoing surgery were qualified for the study. Patients were divided into two groups: those with no healing complications and those with stump healing complications. Medical records of both groups were analyzed for risk factors for impaired healing. The obtained data were subjected to statistical analysis. Results Patients with impaired stump healing most often had minimal bleeding and higher ASA scores compared to patients without healing complications. No differences between the two groups were found for the remaining parameters. Patients with complications needed an average of 28 days to heal the wound and spent an average of 40 days in hospital, compared to 14 and 21 days, respectively, for patients without complications. The percentage of deaths in the group of patients with complications was also significantly higher (35%) than in the group of patients without complications (5%). Conclusions Statistically significant factors increasing the risk of impaired stump healing include high ASA scale and minimal muscle bleeding during surgery. Patients who experienced this complication are at greater risk of prolonged hospitalization and death in the postoperative period. This study showed statistically significant risk factors for impaired stump healing following amputation and confirmed the negative impact of this complication on the length of hospitalization and risk of death.

Increased complications following failed hypospadias repairs suggest that impaired wound healing is a contributing factor. We used perioperative hyperbaric oxygen therapy to promote wound healing determined by graft take in staged tubularized autograft reoperations using oral graft.Hyperbaric oxygen therapy was recommended for patients with 3 or more failed hypospadias repairs, comprising 20 preoperative and 10 postoperative sessions. All patients underwent reoperative staged tubularized autograft repair using oral mucosa. Graft lengths and widths were measured at grafting and again at the second stage, from which graft area was calculated. The primary outcomes were percent graft contracture and graft failure, defined as contracture 50% or greater. Patients who received hyperbaric oxygen therapy were compared to other patients who underwent reoperative staged tubularized autograft who did not receive therapy.Among 57 patients 32 received hyperbaric oxygen therapy and 25 did not as they had fewer than 3 prior repairs, or were not able to receive treatment due to insurance issues or lack of local availability. Grafts were healthier in those receiving hyperbaric oxygen therapy, with significantly less percent area contracture (9% vs 26%, p=0.04) and graft failure (6% vs 28%, p=0.03) compared to those not receiving therapy, although treated patients had significantly more prior failed hypospadias repairs.Hyperbaric oxygen therapy improved graft take in hypospadias reoperations. This observation also calls attention to wound healing as another variable to consider in hypospadias surgery.

Fibrosis affects all vital organs accounting for a staggering 45% of deaths worldwide and no effective therapies are currently available. Unresolved inflammation triggers downstream signaling events that lead to organ fibrosis. In recent years, proinflammatory cytokine Interleukin-17 (IL-17) has been implicated in several chronic inflammatory diseases that often culminate in organ damage followed by impaired wound healing and fibrosis. In this review, we outline the contribution of the IL-17 in mediating fibrotic diseases in various organs. A comprehensive understanding of the inflammatory events, and particularly the details of IL-17 signaling in vivo, could be beneficial in designing new therapeutic or preventive approaches to treat fibrosis. Additionally, understanding organ-specific differences in IL-17 activity could lead to targeted therapies and help spare other organs from unwanted side effects.

Diabetes mellitus-induced hyperglycemia is associated with a number of pathologies such as retinopathy, nephropathy, delayed wound healing, and diabetic peripheral neuropathy (DPN). Approximately 50% of patients with diabetes mellitus will develop DPN, which is characterized by disrupted sensory and/or motor functioning, with treatment limited to pain management. Zebrafish ( Danio rerio) are an emerging animal model used to study a number of metabolic disorders, including diabetes. Diabetic retinopathy, nephropathy, and delayed wound healing have all been demonstrated in zebrafish. Recently, our laboratory has demonstrated that following the ablation of the insulin-producing β-cells of the pancreas (and subsequent hyperglycemia), the peripheral nerves begin to show signs of dysregulation. In this study, we take a different approach, taking advantage of the transdermal absorption abilities of zebrafish larvae to extend the period of hyperglycemia. Following 5 days of 60 mM d-glucose treatment, we observed motor axon defasciculation, disturbances in perineurial glia sheath formation, decreased myelination of motor axons, and sensory neuron mislocalization. This study extends our understanding of the structural changes of the peripheral nerve following induction of hyperglycemia and does so in an animal model capable of potential DPN drug discovery in the future. NEW & NOTEWORTHY Zebrafish are emerging as a robust model system for the study of diabetic complications such as retinopathy, nephropathy, and impaired wound healing. We present a novel model of diabetic peripheral neuropathy in zebrafish in which the integrity of the peripheral nerve is dysregulated following the induction of hyperglycemia. By using this model, future studies can focus on elucidating the underlying molecular mechanisms currently unknown.

Introduction: Wound healing requires energy and is a catabolic process. Patients who are severely malnourished demonstrate impaired wound healing and predisposition to infection. They also suffer deficient immune mechanisms. The degree of malnutrition is estimated on the basis of weight loss during the past 6 months, physical findings and plasma protein assessment. The purpose of this study was to investigate serum albumin and BMI as predictors of postoperative mortality and morbidity. Materials and Methodology: Total of 117 patients were included in the study admitted in KIMS Hubli from November 2012 to June 2014. Results and Conclusion: In this study serum albumin 3.5g/dl. But BMI did not show any statistically significance in the study.

Background and Objectives: Wound healing is a dynamic process that can be compromised in patients with chronic and metabolic conditions or unhealthy lifestyles. Numerous medical substances designed for topical use, charged with compounds that promote the healing process, have been developed to improve wound healing, especially in compromised subjects. The present study aimed to extend our understanding of the in vivo effects of a hyaluronic acid gel charged with amino acids (HAplus gel, Aminogam gel® Errekappa Euroterapici spa, Milan, Italy) and study the in vitro effects of the same gel charged with additional substances in an attempt to optimize its formulation. Materials and Methods: In a randomized controlled split-mouth clinical and histological trial, HAplus gel was tested on the gingival tissue of the lower third molar post-extraction socket. The gingiva was collected at the time of extraction (T0) and ten days after the extraction (T1) to be histologically analyzed. During the second stage of the study, culture media with HAplus gel and vitamin C and E at different concentrations (TEST) were tested on human gingival fibroblasts and compared to the HAplus-enriched medium (HA-Control). Results: Histological and immunohistochemical analysis of collected gingiva showed higher microvascular density and collagen fibers organized in closely packed and well-oriented bundles in sites treated with HAplus gel. In the in vitro study, all TEST groups showed an increased viability from 24 h to 48 h. After 24 h, the viability percentage in all experimental groups was below 100% of the HA-Control, demonstrating a mild toxicity. After 48 h from seeding, the TEST groups’ viability grew significantly compared to HA-Control. Conclusions: These encouraging preliminary results suggest that the use of HAplus gel enriched with vitamins C and E may be beneficial in patients with conditions that impair soft tissue healing.

Impaired wound healing is an immense medical challenge, and while autologous skin grafting remains the “gold-standard” therapeutic option for repairing wounds that cannot be closed by primary or secondary intention, it is limited by substantial donor site morbidity. We previously developed the alternative approach of harvesting full-thickness skin tissue in the form of “micro skin tissue columns” (MSTCs), without causing scarring or any other long-term morbidity. In this study we investigated how MSTC treatment affects the different cellular processes involved in wound healing. We found that MSTC-derived cells were able to remodel and repopulate the wound volume, and positively impact multiple aspects of the wound healing process, including accelerating re-epithelialization by providing multiple cell sources throughout the wound area, increasing collagen deposition, enhancing dermal remodeling, and attenuating the inflammatory response. These effects combined to enhance both epidermal and dermal wound healing. This MSTC treatment approach was designed for practical clinical use, could convey many benefits of autologous skin grafting, and avoids the major drawback of donor site morbidity.

Outpatient surgeries have increased dramatically over the last three decades. Recovery Room protocols for nursing in ambulatory settings can improve quality of care through standardization of practice to follow evidence-based guidelines. Protocols should be developed using a multidisciplinary team. Fast-track protocols, where patients are able to bypass phase I of recovery, can lead to decreased length of stay and are an economically efficient model. Pain assessment scales are important for the development of pain management protocols that should employ a multimodal approach to pain management. Postoperative nausea and vomiting is a common cause of delayed discharge and unplanned admissions. Nursing protocols for postoperative nausea and vomiting that rely on nurse assessments, communication, and protocolized treatments may further improve quality of care. Hypothermia protocols should similarly be developed to correct hypothermia aggressively due to associated risks including impaired wound healing, adverse cardiac events, altered drug metabolism, and coagulopathies.

Hypergranulation and crust formation after cranial neurosurgery is rare. We report three patients with an uncommon form of hypergranulation with extensive crust formation after cranial neurosurgery, associated with a St. Aureus infection of the scalp, and propose that this is a form of pyogenic dermatitis, as is commonly seen among domestic animals with a coat of fur. It can be treated conservatively. We propose a treatment algorithm.

Background: Wound healing problems following abdominoplasty may be a result of impaired tissue perfusion. This study evaluated the impact a standard abdominoplasty may have on abdominal skin perfusion. Methods: A standard abdominoplasty was performed in 16 patients. Dynamic infrared thermography (DIRT) using a mild and a stronger cold challenge was performed pre-, intra-, and postoperatively on day 1, 2, and in week 6. The abdomen was divided into Huger’s vascular zones. A two-tailed t test was used to evaluate differences in mean temperature between zones. Statistical significance was defined as P < 0.05. Results: Two patients suffered wound healing problems. Abdominal skin perfusion showed a hyperaemic state on day 1, day 2, and week 6, postoperatively. Hotspots in zones I and II had all disappeared at the end of surgery and on day 1, except in the cranial part of zone I. Hotspots reappeared in zones I and II during day 2. A statistically significant difference between zones I and II was seen on day 1 and 2, with zone II being cooler. This difference had disappeared in week 6 for the mild cold challenge but not for the stronger cold challenge. Conclusions: A standard abdominoplasty has a significant impact on abdominal skin perfusion. The skin perfusion is a dynamic process with a gradual improvement over time. The strongest effect was seen in zone II near the lower transverse incision line, where skin perfusion was the least. Such may contribute to impaired wound healing at this site

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in granulocytes in chronic wounds, and we show that patients with the junctional form of EB have significantly more cells infiltrating their wounds compared with patients with recessive dystrophic EB. Finally, we identify subsets of granulocytes and T lymphocytes present in all wounds paving the way for single cell profiling of innate and adaptive immune cells with relevance to wound pathologies. In summary, our study delineates findings in EB that have potential relevance for all chronic wounds, and presents a method of cellular isolation that has wide reaching clinical application.

Keloids are pathological scars that grow over time and extend beyond the initial site of injury after impaired wound healing. These scars frequently recur and rarely regress. They are aesthetically disfiguring, can cause pain, itching, discomfort as well as psychological stress, often affecting quality of life. Many treatment modalities, including surgical and non-surgical, have been explored and have been reported to be beneficial; however, none have been absolutely satisfactory or optimal for the treatment of all keloid subtypes to date. This poses a major challenge to clinicians. Often, a combinational therapeutic approach appears to offer the best results with higher patient satisfaction compared to monotherapy. The aetiopathogenesis of keloids is not fully elucidated; however, with recent advances in molecular biology and genetics, insight is being gained on the complex process of scar formation and hence new therapeutic and management options for keloids. In this paper, we explore the literature and summarise the general concepts surrounding keloid development and review both current (corticosteroids, surgical excision, silicone-based products, pressure therapy, radiotherapy, cryotherapy, laser therapy, imiquimod and 5-fluorouracil) and emerging (stem cell therapy, mitomycin C, verapamil, interferons, bleomycin, botulinum toxin type A and angiotensin-converting enzyme inhibitors) treatments. Increased knowledge and understanding in this area may potentially lead to the discovery and development of novel therapeutic options that are more efficacious for all keloid types. Lay Summary [Formula: see text] Keloids are problematic scars that are difficult to treat and manage. The aetiopathogenesis of keloids is not clear; however, recent advances in molecular biology and genetics are beginning to shed light on the underlying mechanisms implicated in keloid scar formation which will hopefully lead to the development of treatment options for all keloid types. This review summarises current and emerging therapies.

Introduction Wound healing disturbances as possible side effects of calcitonin gene-related peptide (CGRP) antibody treatment have been discussed previously but not yet described in humans. Basic research suggests that calcitonin gene-related peptide plays an important role in keratinocyte migration, vascularization and immune response and lack of calcitonin gene-related peptide may lead to impaired wound healing. Case A 51-year-old female migraine patient was treated with the CGRP receptor antibody erenumab for 6 months, which led to a relevant reduction of migraine days. During the treatment, two periods of severely impaired wound healing occurred after a trivial skin injury without spatial relation to the injection site. Skin biopsy confirmed a deep perivascular and interstitial lymphohistiocytic infiltrate with admixed eosinophils, ulceration of the epithelium, a heavy edema of the papillary dermis and focally thrombosed vessels. Conclusion Impaired wound healing might be relevant side effects of CGRP antibody therapy and anamnesis within the course of treatment should also include possible observation of impaired wound healing or planned surgery.

Appropriate nutrition is a key component of burn treatment and should be regarded as an integral part of the therapeutic process in burn patients. A nutritional intervention plan should not only allow for adequate quantities of energy and protein but also carefully consider the supply of macro- and micronutrients. As a result of the severe inflammatory response, oxidative stress, and hypermetabolic state, accompanied by often extensive exudation in burn patients, there is a considerable loss of macro- and micronutrients, including essential trace elements. This leads to certain complications, involving e.g. more frequent infections and impaired wound healing. Our current body of knowledge is still insufficient, and the studies carried out to date focus for the most part on the imbalances in trace elements, such as copper (Cu), selenium (Se), and zinc (Zn). Nevertheless, there are many other trace elements involved in immune functions, regulating gene expression or antioxidant defense, and many of those have not been properly investigated in a clinical setting. Due to the insufficient amount of unambiguous literature data and relatively few, often dated, studies carried out with small patient groups, further evaluation of macro- and microelements in burn patients seems indispensable, e.g. to bring up to date local nutritional protocols.

Impaired healing leading to the formation of ulcerated wounds is a critical concern in patients with diabetes. Abnormalities in extracellular matrix (ECM) production and remodeling contribute to tissue dysfunction and delayed healing. Specifically, diabetes-induced changes in the expression and/or activity of structural proteins, ECM-modifying enzymes, proteoglycans, and matricellular proteins have been reported. In this review, we provide a summary of the key ECM molecules and associated changes in skin and diabetic wounds. Such information should allow for new insights in the understanding of impaired wound healing and lead to the development of ECM-based therapeutic strategies., Highlights • Wound healing is largely impaired in diabetes due, in part, to dysfunction and dysregulation of extracellular matrix. • This review gives a brief summary of the alterations of key ECM molecules in diabetes. • We also try to elucidate how hyperglycemia impacts ECM and anticipate how these changes contribute to the pathological state of diabetic wounds.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

This chapter focuses on interactions between bone marrow monopoiesis and skin wound healing in normal and diabetic settings. First, the importance and functions of monocytes/macrophages (Mo/Mɸ) in skin wound healing are reviewed as well as the role of Mo/Mɸ dysregulation in impaired wound healing in diabetes. Next, the sources of wound Mɸ are reviewed along with the impact of skin wounding on monopoiesis and the contribution of such wounding-induced monopoiesis to populations of wound Mɸ. Further, the evidence that diabetes increases monopoiesis is reviewed along with the contribution of diabetes-enhanced monopoiesis to increased Mɸ numbers in diabetic wounds and consequent impaired wound healing.

This chapter provides a systematic view of the biomaterial technology for treating cutaneous wounds in diabetic conditions. It starts by presenting the elements, characteristics, and processes that result in impaired wound healing. Also, it explains the main aspects of the physiochemistry of the structure and fabrication of biomaterials to settle the hydration, oxygenation, or infection control requirements in the diabetic wound bed. By the end of the chapter, the synergistic effect of the administration of growth factors, drugs, natural extracts, genes, or cells on diabetic wound healing using biomaterials with a role beyond as a simple vehicle are discussed.

Chronic leg ulcer is one of the diabetic complications causing continuous pain and higher mortality risk. The therapeutic treatment of chronic diabetic wounds can be studied through animal models which simulate the human pathology. Experimental diabetes in mice induced by streptozotocin (STZ) is an easy method with low cost. There have been several studies using STZ for diabetic mice model of cutaneous excisional wound. However, those procedures are different in many factors such as dose of STZ, mouse weight, blood glucose level and the method for assessing health status in mice. We have constructed the criteria to evaluate the health status of the experimental mice including skin color, fur condition, ability to move and body condition. These criteria of health status wereused together with the blood glucose level to evaluate the male mice’s sensitivity to a single high dose (100-150 mg/kg) of STZ. Approximately 40 % of 20–28 g weighted mice, which were injected by 125 mg/kg STZ, developed diabetes in a good health status in the first two weeks after injection. Mice with blood glucose level higher than 200 mg/dL had damaged islet and stably high blood glucose as well as stable health status after two weeks carrying wounds. The wound healing process of the diabetic wounded mice occured relatively slower than that of the control group (non diabetic). The model of diabetic wounded mice has been used to evaluate of the wound healing effect of the rhPDGF-BB protein which has been used in the treatment of chronic wounds caused by human diabetes.

Clinical sequelae of irradiation result in tissue devitalization (e.g., ischemia, fibrosis, and atrophy) where wound healing capacity is impaired. Fat-derived products may work to treat such pathology.Nonlethal irradiation at various doses (5, 10, and 15 Gy) and frequencies (one to three times on sequential days) was delivered to dorsal skin of nude mice, and subsequent gross and microscopic changes were evaluated for up to 4 weeks. Cutaneous punch wounds were then created to compare wound healing in irradiated and nonirradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells, centrifuged fat tissue, or micronized cellular adipose matrix, and the therapeutic impact was monitored for up to 15 days.Nude mice given total doses greater than 15 Gy spontaneously developed skin ulcers, and radiation damage was dose-dependent; however, a fractionated irradiation protocol was able to reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5 to 15 Gy) impairment of wound healing was also evident. At the highest dosage (15 Gy three times), open wounds persisted on day 15. However, wounds injected with cultured adipose-derived stem cells were nearly healed on day 12, and those treated with injection of centrifuged fat or micronized tissue healed faster than untreated controls (p0.05). There was no significant differences between treated groups.Tissue devitalization by irradiation was dose-dependent, although fractionated protocols helped to reduce it. Adipose-derived stem cells and other fat-derived products harboring adipose-derived stem cells successfully revitalized irradiated tissues and accelerated wound healing.

Aims The classical longitudinal incision used for the direct anterior approach (DAA) to the hip does not follow the tension lines of the skin and can lead to impaired wound healing and poor cosmesis. The purpose of this retrospective study was to determine the satisfaction with the scar, and functional and radiographic outcomes comparing the classic longitudinal incision with a modified skin crease ‘bikini’ when the DAA is used for total hip arthroplasty (THA). Patients and Methods A total of 964 patients (51% female; 59% longitudinal, 41% ‘bikini’) completed a follow-up questionnaire between two and four years postoperatively, including the Oxford Hip Score (OHS), the University of North Carolina ‘4P’ scar scale (UNC4P) and two items for assessing the aesthetic appearance of the scar and symptoms of numbness. The positioning of the components, rates of heterotopic ossification (HO) and rates of revision were assessed. Results The mean OHS was similar in both groups (p = 0.41). The mean UNC4P total score was slightly better (p = 0.01) and the proportion of patients who were very satisfied with the cosmetic aspects of the scar was higher in the ‘bikini’ group (p Conclusion We found that a short oblique ‘bikini’ skin crease incision is safe when used for the DAA at THA, without compromising the positioning of the components or increasing the rate of lateral femoral cutaneous nerve dysaesthesia. Although it leads to a superior scar satisfaction, as it is less extensile, it should be used after having gained experience with the classic longitudinal incision. Cite this article: Bone Joint J 2018;100-B:853–61.

Propolis is a resinous mixture that honey bees collect from the tree buds, sap flows, or other botanical sources. The chemical composition of propolis varies and depends on the geographical area, time of collection, seasonality, illumination, altitude, and food availability during propolis exploitation. The goal of this review is to discuss important concepts including mechanisms of action and therapeutic activities of propolis. The PubMed, ScienceDirect, and Cochrane Library databases were searched for the literature published from January the 1st 2000 to October the 1st 2017. Sixteen animals and three clinical studies were included. A quantitative and qualitative review was performed on the clinical trials and the animal studies were comprehensively overviewed. In this study, the clinical trials have been combined and the results were provided as meta-analysis. Propolis is a non-toxic natural product; however some cases of allergy and contact dermatitis to this compound have been described mainly among beekeepers. An important factor in impaired wound healing is biofilm formation; propolis as an anti-microbial agent can reduce biofilm generation and result in accelerated healing processes. Most of the in vivo studies on various wound models suggested the beneficial roles of propolis on experimental wound healing and this has also been approved in the clinical trial studies. However, there is a lack of information concerning, dose, side effects and clinical effectiveness of propolis on wounds. As the effectiveness of propolis between different products is variable, more characterizations should be done and future investigations comparing different propolis based products and characterization of their specific roles on different models of wounds are highly appreciated.

Objective: Oxidative stress can contribute to impaired wound healing and chronic wounds. Our objective was to test the results of a new antioxidant dressing that could help stop the oxidative stress of cells in the wound bed. Method: A multicentre, prospective case study series was conducted in three Spanish hospitals. The RESVECH 2.0 index was used for healing assessment. Data from each patient was collected by the attending clinical researchers. Data analysis was performed using the statistical concept intention-to-treat (ITT). Descriptive results were presented as frequency and percentages for qualitative variables and mean, standard deviation (SD), range and median for quantitative variables. For analytical-inferential analyses, incidence of healing was calculated for chronic and acute wounds. Relative risk (RR) was used to establish the differences of healing between both types of wounds. Healing was represented by Kaplan-Meier survival curves, and these were compared using the log-rank test. Results: A total of 31 patients with hard-to-heal wounds were recruited. During the 8-week follow-up period, nine wounds (29%) completely healed, of which seven (77.8%) were acute and two (22.2%) chronic. The remaining wounds (22) showed a significant improvement after treatment with the antioxidant dressing. RESVECH 2.0 scores decreased an average of 10.16 points over the 8-week period. Conclusion: The antioxidant dressing could represent an alternative in the dressing landscape for many types of acute and chronic wounds. Partial funding for this project was provided by the Basque Government Department of Economic Development and Competitiveness (Spain) and the European Regional Development Fund under the program GAITEK. Additional funds were also obtained from the Spanish Centre for Development of Industrial Technology (CDTI).

Delayed wound healing and the potentially resulting chronic wounds are a challenging clinical problem. Available therapeutic strategies are limited in both number and efficacy. For developing and establishing novel treatment approaches appropriate clinically relevant animal models are essential. The aim of the study was to establish a reliable and reproducible delayed wound healing model, which simulates the clinical scenario of compromised vascular tissue perfusion (hypoxia/ischemia). Therefore a standard rodent ischemic flap model was modified by challenging the tissue with ascending degrees of ischemia using different surgical approaches (minimal, mild, moderate, and severe ischemic invasive approach). Then a full-thickness circular wound was excised in both the non-/hypoperfused flap area and in the normally perfused contralateral region serving as an internal control. Wound healing progress was compared. Superficial tissue perfusion was measured by Laser Doppler imaging technique, which showed persis...

Impaired wound healing that mimics chronic human skin pathologies is difficult to achieve in current animal models, hindering testing and development of new therapeutic biomaterials that promote wound healing. In this article, we describe a refinement and simplification of the porcine ischemic wound model that increases the size and number of experimental sites per animal. By comparing three flap geometries, we adopted a superior configuration (15 × 10 cm) that enabled testing of twenty 1 cm2 wounds in each animal: 8 total ischemic wounds within 4 bipedicle flaps and 12 nonischemic wounds. The ischemic wounds exhibited impaired skin perfusion for ∼1 week. To demonstrate the utility of the model for comparative testing of tissue regenerative biomaterials, we evaluated the healing process in wounds implanted with highly porous poly (thioketal) urethane (PTK-UR) scaffolds that were fabricated through reaction of reactive oxygen species (ROS)-cleavable PTK macrodiols with isocyanates. PTK-lysine triisocyanate (LTI) scaffolds degraded significantly in vitro under both oxidative and hydrolytic conditions whereas PTK-hexamethylene diisocyanate trimer (HDIt) scaffolds were resistant to hydrolytic breakdown and degraded exclusively through an ROS-dependent mechanism. Upon placement into porcine wounds, both types of PTK-UR materials fostered new tissue ingrowth over 10 days in both ischemic and nonischemic tissue. However, wound perfusion, tissue infiltration and the abundance of pro-regenerative, M2-polarized macrophages were markedly lower in ischemic wounds independent of scaffold type. The PTK-LTI implants significantly improved tissue infiltration and perfusion compared with analogous PTK-HDIt scaffolds in ischemic wounds. Both LTI and HDIt-based PTK-UR implants enhanced M2 macrophage activity, and these cells were selectively localized at the scaffold/tissue interface. In sum, this modified porcine wound-healing model decreased animal usage, simplified procedures, and permitted a more robust evaluation of tissue engineering materials in preclinical wound healing research. Deployment of the model for a relevant biomaterial comparison yielded results that support the use of the PTK-LTI over the PTK-HDIt scaffold formulation for future advanced therapeutic studies.

Introduction It is known that systolic dysfunction (dilated cardiomyopathy) may occur in a high percentage of patients with large TBSA burns. The reversible myocardial depression may be due to many factors: thermal injury, sepsis, severe malnutrition. Malnutrition and delayed wound healing may occur with a combination of primary and secondary protein-energy undernutrition. Methods Serial transthoracic and transesophageal echocardiographic parameters were measured during perioperative care (ejection fraction, fractional shortening, pericardial fluid) in 8 patients with evidence of malnutrition (low BMI, low albumin and prealbumin, muscle wasting) and a delayed presentation to the hospital. Initial echocardiography was performed post-injury day 30 -142; follow-up exams were performed in some patients at 2 years post-injury. Acutely-injured patients or those with sepsis were excluded. Results From 2015–2017, echocardiographic measurements were obtained in 8 patients, ages 7–21. The presenting TBSA ranged from 30–82% and included flame injury, electrical burns, and 1 case of pemphigus vulgaris. The initial ejection fraction ranged from 12–45% in patients with a BMI range of 10–25. The mean initial albumin was 2g/dL; the mean prealbumin was 9.5mg/dL. Two patients had mild to moderate pericardial effusions, which resolved after 1 month of proper nutrition. Selenium deficiency was noted in 1 patient. Four patients required perioperative short-term dobutamine. Conclusions Patients presenting with malnutrition and impaired wound healing all had evidence of cardiomyopathy; however, the degrees of systolic dysfunction varied significantly. BMI, albumin, and prealbumin all had a strong correlation with the degree of myocardial depression. Despite the lower ejection fractions, many patients maintained an adequate cardiac index and did not require inotropic medications. With time and adequate nutrition, cardiac function improved, although many remained with mild dysfunction in the first year. Applicability of Research to Practice This case series demonstrates the continued need for early recognition of malnutrition and cardiomyopathy in this patient population and the need for early intervention. Echocardiographic diagnosis may improve acute perioperative care. In addition, future studies are needed to determine the chronic cardiac effects of reversible dilated cardiomyopathy. Nutrition, refeeding, and perioperative management require a multidisciplinary team.

Disturbed wound healing (DWH) following elective foot and ankle surgery is associated with a number of known risk factors. The purpose of this study was to determine if peripheral artery disease (PAD) is a potential risk factor that contributes to an increase in postoperative DWH. In a case–control study, we analyzed all patients undergoing elective foot and ankle surgery between January 1, 2014 and December 31, 2017 at two institutions and identified 51 patients with postoperative DWH. After matching with 51 control patients without DWH, all 102 patients were evaluated for PAD. The prevalence of PAD was significantly higher in the DWH group compared to the control group (41.2% vs 19.6%, p < 0.01). This difference was even more distinctive for patients with any abnormal ankle–brachial index (ABI) (51.0% vs 19.6%, p < 0.001). After adjustment for diabetes, hypertension, hypercholesterolemia, and smoking, any abnormal ABI or a history of PAD remained an independent risk factor for DWH (odds ratio 3.28; 95% CI 1.24–8.71). In this dual-center study, postoperative DWH was associated with significantly higher rates of PAD. These findings suggest that preoperative evaluation for PAD could be a helpful tool to identify patients at high risk for postoperative wound complications undergoing foot and ankle surgery. This trial is registered with drks.de, number DRKS00012580.

Nutritional support remains an important aspect in the care of critically ill patients, especially those with severe burns. The unique hypermetabolic state occurring after a severe burn can cause metabolic rates to double and is accompanied by severe catabolism. The hypermetabolic state persists for more than a year after severe injury, and if nutritional support does not meet the increased energy expenditures, patients experience significant loss of lean muscle mass, impaired wound healing and immune dysfunction [1, 2]. The goal of nutritional support in the burn patient is to ameliorate and optimize the deranged metabolism and avoid nutritional complications.

Category: General Health Introduction/Purpose: Smoking tobacco is a risk factor for impaired wound healing, infection, delayed fracture healing, and prolonged hospital stay. Smoking cessation prior to surgery has shown a 40% relative risk reduction in total perioperative complications. The primary purpose of this study is to evaluate the impact of preoperative smoking cessation on long-term smoking habits in patients undergoing elective lower extremity orthopaedic surgery. The secondary outcome is patient-reported effectiveness of smoking cessation method. Methods: A retrospective cohort study was performed by identifying all patients who were smokers that were required to quit and subsequently had a normal nicotine/cotinine serum test prior to lower extremity orthopaedic surgery. Attempts were made to contact all patients and administer a survey inquiring about demographics, medical history, smoking history, smoking cessation process, and current smoking status. Results: Of 36 eligible patients, 23 completed the survey. Eleven patients identified as current non-smokers (48%) at the time of survey follow-up (mean follow-up 55 months with a range of 12 to 88 months). Of these 11, 82% said they were very likely to continue to refrain from smoking. Twelve patients identified as current smokers at the time of survey, over half of whom ceased smoking for at least three months perioperatively. The reasons for resuming smoking were “stress” (45%), ”falling back into the habit” (37%), and due to “friends who smoke” (18%). The majority of smoking patients (92%) decreased the number of cigarettes they smoked regularly. The most effective smoking cessation techniques were ”cold turkey”, “non-nicotine medication”, and ”trans-dermal nicotine patches”. Conclusion: Elective surgery offers a unique opportunity for smoking cessation. Of 23 patients required to quit smoking prior to surgery, 48% maintained smoking cessation at least one year postoperatively. Of the 12 patients who relapsed, 55% stated that they did not resume smoking until at least three months postoperatively, suggesting that this particular period may be an important time for intensified smoking cessation counseling.

Inflammation after trauma is both critical to normal wound healing and may be highly detrimental when prolonged or unchecked with the potential to impair physiologic healing and promote de novo pathology. Mechanical strain after trauma is associated with impaired wound healing and increased inflammation. The exact mechanisms behind this are not fully elucidated. Neutrophil extracellular traps (NETs), a component of the neutrophil response to trauma, are implicated in a range of pro-inflammatory conditions. In the current study, we evaluated their role in linking movement and inflammation. We found that a link exists between the disruption and amplification of NETs which harbors the potential to regulate the wound's response to mechanical strain, while leaving the initial inflammatory signal necessary for physiologic wound healing intact.

Suturing type is important because impaired wound healing can increase the cost of the treatment...