Biology of chronic wounds and new treatment strategies

2014 ◽  
Vol 29 (1_suppl) ◽  
pp. 165-167 ◽  
Author(s):  
Catherine van Montfrans ◽  
Myrte Stok ◽  
Maud Geerkens
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Treatment Strategies ◽  
Skin Substitutes ◽  
Related Factors ◽  
Impaired Wound Healing ◽  
Healing Tissue ◽  
Biologic Process ◽  
Matrix Components ◽  
New Treatment

Impaired wound healing is the result of the interplay between patient-related factors, wound-related factors, skill and knowledge of the healthcare professional and resources and treatment-related factors. The study of wound-related factors learns us that healing is a very complex biologic process. Both ‘seed’ (differentiated and stem cells) and ‘soil’ (e.g. cytokines/chemokines, growth factors, matrix components) are essential for effective wound healing. Tissue engineering for chronic wounds has the potential to improve healing by providing an ‘ideal’ combination of cells and their local microenviroment. In this contribution we discuss new treatment strategies to improve wound-related factors by biomaterials, skin substitutes and stem cell-based therapies.

scholarly journals Inhibition of 11β-HSD1 Expression by Insulin in Skin: Impact for Diabetic Wound Healing

2020 ◽  
Vol 9 (12) ◽  
pp. 3878
Author(s):  
Christina B. Brazel ◽  
Jan C. Simon ◽  
Jan P. Tuckermann ◽  
Anja Saalbach
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Health Care Systems ◽  
Stress Hormones ◽  
Myeloid Cells ◽  
Inhibitory Effect ◽  
Related Factors ◽  
Delayed Wound Healing ◽  
Impaired Wound Healing ◽  
Obesity And Diabetes

Chronic, non-healing wounds impose a great burden on patients, professionals and health care systems worldwide. Diabetes mellitus (DM) and obesity are globally highly prevalent metabolic disorders and increase the risk for developing chronic wounds. Glucocorticoids (GCs) are endogenous stress hormones that exert profound effects on inflammation and repair systems. 11-beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) is the key enzyme which controls local GC availability in target tissues such as skin. Since treatment with GCs has detrimental side effects on skin integrity, causing atrophy and delayed wound healing, we asked whether the dysregulated expression of 11β-HSD1 and consequently local GC levels in skin contribute to delayed wound healing in obese, diabetic db/db mice. We found increased expression of 11β-HSD1 during disturbed wound healing and in the healthy skin of obese, diabetic db/db mice. Cell analysis revealed increased expression of 11β-HSD1 in fibroblasts, myeloid cells and dermal white adipose tissue from db/db mice, while expression in keratinocytes was unaffected. Among diabetes- and obesity-related factors, insulin and insulin-like growth factor 1 down-regulated 11β-HSD1 expression in fibroblasts and myeloid cells, while glucose, fatty acids, TNF-α and IL-1β did not affect it. Insulin exerted its inhibitory effect on 11β-HSD1 expression by activating PI3-kinase/Akt-signalling. Consequently, the inhibitory effect of insulin is attenuated in fibroblasts from insulin-resistant db/db mice. We conclude that insulin resistance in obesity and diabetes prevents the down-regulation of 11β-HSD1, leading to elevated endogenous GC levels in diabetic skin, which could contribute to impaired wound healing in patients with DM.

scholarly journals Mechanistic Actions of microRNAs in Diabetic Wound Healing

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2228
Author(s):  
Marija Petkovic ◽  
Anja Elaine Sørensen ◽  
Ermelindo Carreira Leal ◽  
Eugenia Carvalho ◽  
Louise Torp Dalgaard
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Gene Expression Regulation ◽  
Treatment Strategies ◽  
Impaired Wound Healing ◽  
Complex Biological Process ◽  
Efficacious Treatment ◽  
Health And Disease ◽  
Diabetic Wound Healing ◽  
Healing Wounds

Wound healing is a complex biological process that is impaired under diabetes conditions. Chronic non-healing wounds in diabetes are some of the most expensive healthcare expenditures worldwide. Early diagnosis and efficacious treatment strategies are needed. microRNAs (miRNAs), a class of 18–25 nucleotide long RNAs, are important regulatory molecules involved in gene expression regulation and in the repression of translation, controlling protein expression in health and disease. Recently, miRNAs have emerged as critical players in impaired wound healing and could be targets for potential therapies for non-healing wounds. Here, we review and discuss the mechanistic background of miRNA actions in chronic wounds that can shed the light on their utilization as specific wound healing biomarkers.

scholarly journals Targeting Oxidative Stress and Mitochondrial Dysfunction in the Treatment of Impaired Wound Healing: A Systematic Review

Antioxidants ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 98 ◽  
Author(s):  
Mariola Cano Sanchez ◽  
Steve Lancel ◽  
Eric Boulanger ◽  
Remi Neviere
Keyword(s):  
Wound Healing ◽  
Mitochondrial Dysfunction ◽  
Chronic Wounds ◽  
Ros Generation ◽  
Nuclear Factor ◽  
Impaired Wound Healing ◽  
Pyrin Domain ◽  
Low Concentrations ◽  
Pathway Inhibition ◽  
Healing Processes

Wound healing is a well-tuned biological process, which is achieved via consecutive and overlapping phases including hemostasis, inflammatory-related events, cell proliferation and tissue remodeling. Several factors can impair wound healing such as oxygenation defects, aging, and stress as well as deleterious health conditions such as infection, diabetes, alcohol overuse, smoking and impaired nutritional status. Growing evidence suggests that reactive oxygen species (ROS) are crucial regulators of several phases of healing processes. ROS are centrally involved in all wound healing processes as low concentrations of ROS generation are required for the fight against invading microorganisms and cell survival signaling. Excessive production of ROS or impaired ROS detoxification causes oxidative damage, which is the main cause of non-healing chronic wounds. In this context, experimental and clinical studies have revealed that antioxidant and anti-inflammatory strategies have proven beneficial in the non-healing state. Among available antioxidant strategies, treatments using mitochondrial-targeted antioxidants are of particular interest. Specifically, mitochondrial-targeted peptides such as elamipretide have the potential to mitigate mitochondrial dysfunction and aberrant inflammatory response through activation of nucleotide-binding oligomerization domain (NOD)-like family receptors, such as the pyrin domain containing 3 (NLRP3) inflammasome, nuclear factor-kappa B (NF-κB) signaling pathway inhibition, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2).

scholarly journals From Grafts to Human Bioengineered Vascularized Skin Substitutes

2020 ◽  
Vol 21 (21) ◽  
pp. 8197
Author(s):  
Wasima Oualla-Bachiri ◽  
Ana Fernández-González ◽  
María I. Quiñones-Vico ◽  
Salvador Arias-Santiago
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Chronic Wounds ◽  
Thermal Regulation ◽  
Skin Substitute ◽  
Skin Substitutes ◽  
Normal Wound Healing ◽  
Physiological Homeostasis ◽  
Promising Solution ◽  
Native Skin

The skin plays an important role in the maintenance of the human’s body physiological homeostasis. It acts as a coverage that protects against infective microorganism or biomechanical impacts. Skin is also implied in thermal regulation and fluid balance. However, skin can suffer several damages that impede normal wound-healing responses and lead to chronic wounds. Since the use of autografts, allografts, and xenografts present source limitations and intense rejection associated problems, bioengineered artificial skin substitutes (BASS) have emerged as a promising solution to address these problems. Despite this, currently available skin substitutes have many drawbacks, and an ideal skin substitute has not been developed yet. The advances that have been produced on tissue engineering techniques have enabled improving and developing new arising skin substitutes. The aim of this review is to outline these advances, including commercially available skin substitutes, to finally focus on future tissue engineering perspectives leading to the creation of autologous prevascularized skin equivalents with a hypodermal-like layer to achieve an exemplary skin substitute that fulfills all the biological characteristics of native skin and contributes to wound healing.

scholarly journals Shedding Light on a New Treatment for Diabetic Wound Healing: A Review on Phototherapy

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Nicolette N. Houreld
Keyword(s):  
Wound Healing ◽  
Laser Irradiation ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
Intensity Laser

Impaired wound healing is a common complication associated with diabetes with complex pathophysiological underlying mechanisms and often necessitates amputation. With the advancement in laser technology, irradiation of these wounds with low-intensity laser irradiation (LILI) or phototherapy, has shown a vast improvement in wound healing. At the correct laser parameters, LILI has shown to increase migration, viability, and proliferation of diabetic cellsin vitro; there is a stimulatory effect on the mitochondria with a resulting increase in adenosine triphosphate (ATP). In addition, LILI also has an anti-inflammatory and protective effect on these cells. In light of the ever present threat of diabetic foot ulcers, infection, and amputation, new improved therapies and the fortification of wound healing research deserves better prioritization. In this review we look at the complications associated with diabetic wound healing and the effect of laser irradiation bothin vitroandin vivoin diabetic wound healing.

Role of Nitric Oxide in Wound Healing

2002 ◽  
Vol 4 (1) ◽  
pp. 5-15 ◽  
Author(s):  
Beverly B. Childress ◽  
Joyce K. Stechmiller
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Growth Factors ◽  
Animal Studies ◽  
Chronic Wounds ◽  
Current Knowledge ◽  
Wound Care ◽  
Impaired Wound Healing ◽  
Normal Wound Healing ◽  
Age Related

Chronic wounds mainly affect elderly individuals and persons with comorbid diseases due to a compromised immune status. An age-related decline in immune function deters proper healing of wounds in an orderly and timely manner. Thus, older adults with 1 or more concomitant illnesses are more likely to experience and suffer from a nonhealing wound, which may drastically decrease their quality of life and financial resources. Novel therapies in wound care management rely heavily on our current knowledge of wound healing physiology. It is well established that normal wound healing occurs sequentially and is strictly regulated by pro-inflammatory cytokines and growth factors. A multitude of commercial products such as growth factors are available; however, their effectiveness in healing chronic wounds has yet to be proven. Recently, investigators have implicated nitric oxide (NO) in the exertion of regulatory forces on various cellular activities of the inflammatory and proliferative phases of wound healing. Gene therapy in animal studies has shown promising results and is furthering our understanding of impaired wound healing. The purpose of this article is to review the literature on NO and its role in wound healing. A discussion of the physiology of normal healing and the pathophysiology of chronic wounds is provided.

scholarly journals Nanoparticle-Based Therapeutic Approach for Diabetic Wound Healing

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1234 ◽  
Author(s):  
Hariharan Ezhilarasu ◽  
Dinesh Vishalli ◽  
S. Thameem Dheen ◽  
Boon-Huat Bay ◽  
Dinesh Kumar Srinivasan
Keyword(s):  
Wound Healing ◽  
High Surface ◽  
Treatment Strategies ◽  
Foot Ulcer ◽  
Volume Ratio ◽  
Therapeutic Drug ◽  
Target Tissue ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

Diabetes mellitus (DM) is a common endocrine disease characterized by a state of hyperglycemia (higher level of glucose in the blood than usual). DM and its complications can lead to diabetic foot ulcer (DFU). DFU is associated with impaired wound healing, due to inappropriate cellular and cytokines response, infection, poor vascularization, and neuropathy. Effective therapeutic strategies for the management of impaired wound could be attained through a better insight of molecular mechanism and pathophysiology of diabetic wound healing. Nanotherapeutics-based agents engineered within 1–100 nm levels, which include nanoparticles and nanoscaffolds, are recent promising treatment strategies for accelerating diabetic wound healing. Nanoparticles are smaller in size and have high surface area to volume ratio that increases the likelihood of biological interaction and penetration at wound site. They are ideal for topical delivery of drugs in a sustained manner, eliciting cell-to-cell interactions, cell proliferation, vascularization, cell signaling, and elaboration of biomolecules necessary for effective wound healing. Furthermore, nanoparticles have the ability to deliver one or more therapeutic drug molecules, such as growth factors, nucleic acids, antibiotics, and antioxidants, which can be released in a sustained manner within the target tissue. This review focuses on recent approaches in the development of nanoparticle-based therapeutics for enhancing diabetic wound healing.

scholarly journals Insights into Host–Pathogen Interactions in Biofilm-Infected Wounds Reveal Possibilities for New Treatment Strategies

Antibiotics ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 396
Author(s):  
Hannah Trøstrup ◽  
Anne Sofie Boe Laulund ◽  
Claus Moser
Keyword(s):  
Wound Healing ◽  
Host Response ◽  
Chronic Wounds ◽  
Therapeutic Potential ◽  
Recent Observation ◽  
Treatment Strategies ◽  
Normal Wound Healing ◽  
Inflammatory Phase ◽  
The Impact

Normal wound healing occurs in three phases—the inflammatory, the proliferative, and the remodeling phase. Chronic wounds are, for unknown reasons, arrested in the inflammatory phase. Bacterial biofilms may cause chronicity by arresting healing in the inflammatory state by mechanisms not fully understood. Pseudomonas aeruginosa, a common wound pathogen with remarkable abilities in avoiding host defense and developing microbial resistance by biofilm formation, is detrimental to wound healing in clinical studies. The host response towards P. aeruginosa biofilm-infection in chronic wounds and impact on wound healing is discussed and compared to our own results in a chronic murine wound model. The impact of P. aeruginosa biofilms can be described by determining alterations in the inflammatory response, growth factor profile, and count of leukocytes in blood. P. aeruginosa biofilms are capable of reducing the host response to the infection, despite a continuously sustained inflammatory reaction and resulting local tissue damage. A recent observation of in vivo synergism between immunomodulatory and antimicrobial S100A8/A9 and ciprofloxacin suggests its possible future therapeutic potential.

scholarly journals The Small Molecule NLRP3 Inflammasome Inhibitor MCC950 Does Not Alter Wound Healing in Obese Mice

2018 ◽  
Vol 19 (11) ◽  
pp. 3289 ◽  
Author(s):  
James Lee ◽  
Avril Robertson ◽  
Matthew Cooper ◽  
Kiarash Khosrotehrani
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Nlrp3 Inflammasome ◽  
Chronic Wounds ◽  
Inflammatory Diseases ◽  
Healing Process ◽  
Obese Mice ◽  
Impaired Wound Healing ◽  
Macrophage Polarisation ◽  
Inflammatory Conditions

The incidence of chronic wounds is escalating, and the associated healing process is especially problematic in an aging population with increased morbidity. Targeting increased inflammation in chronic wounds is a promising but challenging therapeutic strategy. Indeed, inflammation and especially macrophages are required for wound healing. As the NLRP3 inflammasome has been implicated with various other inflammatory diseases, in this study, we used MCC950—a selective NLRP3 small molecule inhibitor—on murine models of both acute and chronic wounds. This molecule, while tested for other inflammatory conditions, has never been investigated to reduce topical inflammation driving chronic wounds. We found that there were no significant differences when the treatment was applied either topically or orally in wild-type C57Bl/6 mice and that it even impaired wound healing in obese mice. The treatment was also unable to improve re-epithelialisation or angiogenesis, which are both required for the closure of wounds. We are inclined to believe that MCC950 may inhibit the closure of chronic wounds and that it does not alter wound-associated macrophage polarisation.

scholarly journals Cellular human tissue-engineered skin substitutes investigated for deep and difficult to heal injuries

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Álvaro Sierra-Sánchez ◽  
Kevin H. Kim ◽  
Gonzalo Blasco-Morente ◽  
Salvador Arias-Santiago
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Human Cell ◽  
Chronic Wounds ◽  
Healing Process ◽  
Wound Healing Process ◽  
Future Perspectives ◽  
Skin Substitutes ◽  
Cell Potential ◽  
Engineered Skin Substitutes

AbstractWound healing is an important function of skin; however, after significant skin injury (burns) or in certain dermatological pathologies (chronic wounds), this important process can be deregulated or lost, resulting in severe complications. To avoid these, studies have focused on developing tissue-engineered skin substitutes (TESSs), which attempt to replace and regenerate the damaged skin. Autologous cultured epithelial substitutes (CESs) constituted of keratinocytes, allogeneic cultured dermal substitutes (CDSs) composed of biomaterials and fibroblasts and autologous composite skin substitutes (CSSs) comprised of biomaterials, keratinocytes and fibroblasts, have been the most studied clinical TESSs, reporting positive results for different pathological conditions. However, researchers’ purpose is to develop TESSs that resemble in a better way the human skin and its wound healing process. For this reason, they have also evaluated at preclinical level the incorporation of other human cell types such as melanocytes, Merkel and Langerhans cells, skin stem cells (SSCs), induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs). Among these, MSCs have been also reported in clinical studies with hopeful results. Future perspectives in the field of human-TESSs are focused on improving in vivo animal models, incorporating immune cells, designing specific niches inside the biomaterials to increase stem cell potential and developing three-dimensional bioprinting strategies, with the final purpose of increasing patient’s health care. In this review we summarize the use of different human cell populations for preclinical and clinical TESSs under research, remarking their strengths and limitations and discuss the future perspectives, which could be useful for wound healing purposes.

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