Normal Wound Healing Research Articles

Exploring effect of M2 macrophages on experimental full-thickness wound healing in streptozotocin-induced diabetic rats.

Diabetes mellitus is one of the most prevalent medical conditions, in both humans and animals. People with diabetes mellitus often experience slower than normal wound healing, making it a serious health concern. This study investigates the effect of M2 differentiated macrophages on full-thickness wound healing in white Westar rats exposed to streptozocin 70 mg/kg. A full-thickness skin defect with dimensions of 2 × 2 cm was created on the back of all the animals, and their blood sugar was simultaneously assessed. The monocytes were isolated from blood samples using the plastic adherence method and were exposed to dexamethasone (5-10 μ) for 24 h. Subsequently, they were washed with PBS and incubated in fresh cell culture medium for 5 days. The differentiated M2 cells were injected into four points of the experimental ulcers of the treatment group. Macroscopic and microscopic changes were evaluated and compared over a period of two weeks between the test and control groups. The infusion of these cells a few days after wounding enhances wound healing parameters significantly, as evidenced by an increase in germinating tissue formation, wound contraction, inflammation reduction, and collagen increase in the treated group.

Theruptor novo: wound dressing for diabetic foot ulcer

One of the main risk factor affecting the normal wound healing process of is diabetes. India being the capital for diabetes, has a prevalence of 9.6% with 74 million patients living with diabetes and is expected to be 124 million by 2045. The most dreadful complication of diabetes mellitus is the diabetic foot ulcer. Foot ulcer and amputation are among the leading reasons for high morbidity, healthcare costs and mortality in diabetes patients. Numerous things must come together for a chronic wound to heal, and one crucial component of care is the use of wound dressings and these should create an ideal environment for healing while safeguarding the site from infection and additional damage. A diabetic patient presented with a non-healing diabetic foot ulcer (10.83 cm2) with severe loss of protective sensation, exposed excised fourth and fifth metatarsals and he was treated and followed up with regular normal saline washes and Theruptor Novo dressings. The wound started to show signs of healing and within 7 weeks, the wound healed with complete epithelization. Theruptor Novo dressing was helpful in terms of good granulation tissue growth and epithe­lialization over time with good exudate management. Theruptor Novo, a non-adherent dressing with unique antimicrobial action cab be useful in managing diabetic foot ulcers.

Wound-healing plasticity enables clonal expansion of founder progenitor cells in colitis.

Chronic colonic injury and inflammation pose high risks for field cancerization, wherein injury-associated mutations promote stem cell fitness and gradual clonal expansion. However, the long-term stability of some colitis-associated mutational fields could suggest alternate origins. Here, studies of acute murine colitis reveal a punctuated mechanism of massive, neutral clonal expansion during normal wound healing. Through three-dimensional (3D) imaging, quantitative fate mapping, and single-cell transcriptomics, we show that epithelial wound repair begins with the loss of structural constraints on regeneration, forming fused labyrinthine channels containing epithelial cells reprogrammed to a non-proliferative plastic state. A small but highly proliferative set of epithelial founder progenitor cells (FPCs) subsequently emerges and undergoes extensive cell division, enabling fluid-like lineage mixing and spreading across the colonic surface. Crypt budding restores the glandular organization, imprinting the pattern of clonal expansion. The emergence and functions of FPCs within a critical window of plasticity represent regenerative targets with implications for preneoplasia.

Targeting estrogen signaling and biosynthesis for aged skin repair.

Non-healing skin wounds are disproportionally prevalent in older adults. Current treatments do not account for the particularities of aged skin and result in inadequate outcomes. Overall, healing chronic wounds in the elderly remains a major unmet clinical need. Estrogens play a critical role in reproduction but also have important actions in non-reproductive organs. Estrogen biosynthesis and signaling pathways are locally activated during physiological wound healing, processes that are inhibited in elderly estrogen-deprived skin. Estrogen deprivation has been shown to be a critical mediator of impaired wound healing in both postmenopausal women and aged men, and topical estrogen application reverses age-associated delayed wound healing in both elderly men and women. These data indicate that adequate estrogen biosynthesis and properly regulated estrogen signaling pathways are essential for normal wound healing and can be targeted to optimize tissue repair in the elderly. However, due to fundamental questions regarding how to safely restore estrogen signaling locally in skin wounds, there are currently no therapeutic strategies addressing estrogen deficiency in elderly chronic wounds. This review discusses established and recent literature in this area and proposes the hypothesis that estrogen plays a pleiotropic role in skin aging and that targeting estrogen signaling and biosynthesis could promote skin repair in older adults.

Primed inflammatory response by fibroblast subset is necessary for proper oral and cutaneous wound healing.

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host-microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired-related homeobox-1 promoter activity (Prx1Cre+) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process. Using a reporter mouse model, we determined that Prx1Cre+ fibroblasts had significantly higher expression of toll-like receptors 2 and 4 compared to other fibroblast populations. In addition, Prx1 immunopositive cells exhibited heightened activation of inflammatory transcription factor NF-κB during the early wound healing process. At the cytokine level, CXCL1 and CCL2 were significantly upregulated by Prx1Cre+ fibroblasts at baseline and upon LPS stimulation. Importantly, lineage-specific knockout to prevent NF-κB activation in Prx1Cre+ fibroblasts drastically impaired both oral and skin wound healing processes, which was linked to reduced macrophage infiltration, failure to resolve inflammation, and clearance of bacteria. Together, our data implicate a pro-healing role of Prx1-lineage fibroblasts by facilitating early macrophage recruitment and bacterial clearance.

Natural Polymeric Hydrogels Encapsulating Small Molecules for Diabetic Wound Healing.

Diabetes is a condition correlated with a high number of diagnosed chronic wounds as a result of a complex pathophysiological mechanism. Diabetic chronic wounds are characterized by disorganized and longer stages, compared to normal wound healing. Natural polymer hydrogels can act as good wound dressings due to their versatile physicochemical properties, represented mainly by high water content and good biocompatibility. Natural bioactive hydrogels are polymers loaded with bioactive compounds providing antibacterial and antioxidant properties, modulation of inflammation and adherence to wounded tissue, compared to traditional dressings, which enables promising future applications for diabetic wound healing. Natural bioactive compounds, such as polyphenols, polysaccharides and proteins have great advantages in promoting chronic wound healing in diabetes due to their antioxidant, anti-inflammatory, antimicrobial, anti-allergic and wound healing properties. The present paper aims to review the wound healing mechanisms underlining the main issues of chronic wounds and those specifically occurring in diabetes. Also, the review highlights the recent state of the art related to the effect of hydrogels enriched with natural bioactive compounds developed as biocompatible functional materials for improving diabetic-related chronic wound healing and providing novel therapeutic strategies that could prevent limb amputation and increase the quality of life in diabetic patients.

Reepithelialization of Diabetic Skin and Mucosal Wounds Is Rescued by Treatment With Epigenetic Inhibitors.

FOXO1 expression in keratinocytes is needed for normal wound healing. In contrast, FOXO1 expression interferes with the closure of diabetic wounds. Using matrix metallopeptidase 9 as a model system, we found that high glucose significantly increased FOXO1-matrix metallopeptidase 9 interactions via increased DNA demethylation, reduced DNA methylation, and increased permissive histone-3 methylation invitro. Inhibitors of DNA demethylation and permissive histone-3 methylation improved the migration of keratinocytes exposed to high glucose invitro and the closure of diabetic skin and mucosal wounds invivo. Inhibition of epigenetic enzymes that alter FOXO1-induced gene expression dramatically improves diabetic healing and may apply to other conditions where FOXO1 has a detrimental role in diabetic complications.

Mice expressing nonpolymerizable fibrinogen have reduced arterial and venous thrombosis with preserved hemostasis

AbstractElevated circulating fibrinogen levels correlate with increased risk for both cardiovascular and venous thromboembolic diseases. In vitro studies show that formation of a highly dense fibrin matrix is a major determinant of clot structure and stability. Here, we analyzed the impact of nonpolymerizable fibrinogen on arterial and venous thrombosis as well as hemostasis in vivo using FgaEK mice that express normal levels of a fibrinogen that cannot be cleaved by thrombin. In a model of carotid artery thrombosis, FgaWT/EK and FgaEK/EK mice were protected from occlusion with 4% ferric chloride (FeCl3) challenges compared with wild-type (FgaWT/WT) mice, but this protection was lost, with injuries driven by higher concentrations of FeCl3. In contrast, fibrinogen-deficient (Fga−/−) mice showed no evidence of occlusion, even with high-concentration FeCl3 challenge. Fibrinogen-dependent platelet aggregation and intraplatelet fibrinogen content were similar in FgaWT/WT, FgaWT/EK, and FgaEK/EK mice, consistent with preserved fibrinogen–platelet interactions that support arterial thrombosis with severe challenge. In an inferior vena cava stasis model of venous thrombosis, FgaEK/EK mice had near complete protection from thrombus formation. FgaWT/EK mice also displayed reduced thrombus incidence and a significant reduction in thrombus mass relative to FgaWT/WT mice after inferior vena cava stasis, suggesting that partial expression of nonpolymerizable fibrinogen was sufficient for conferring protection. Notably, FgaWT/EK and FgaEK/EK mice had preserved hemostasis in multiple models as well as normal wound healing times after skin incision, unlike Fga−/− mice that displayed significant bleeding and delayed healing. These findings indicate that a nonpolymerizable fibrinogen variant can significantly suppress occlusive thrombosis while preserving hemostatic potential in vivo.

Carotid Endarterectomy in a Hostile Neck: To Do or Not to Do

Abstract Carotid endarterectomy (CEA) is the procedure of choice in patients with symptomatic carotid stenosis. However, in patients with hostile necks due to previous surgery or radiotherapy, there is a fear of higher complication rate, blood loss, and poor wound healing. We report two patients with hostile necks in whom we performed standard CEA with no cranial nerve injuries, no stroke, no blood transfusion, and normal wound healing and briefly review the literature.

The capacity of exosomes derived from adipose-derived stem cells to enhance wound healing in diabetes.

The slow healing and nonhealing of diabetic wounds have long posed challenges for clinical practitioners. In the presence of elevated glucose levels, the body's regulatory mechanisms undergo alterations that impede normal wound healing processes, including cell proliferation, cytokine release, and growth factor activity. Consequently, the advancement of stem cell technology has sparked growing interest in utilizing stem cells and their derivatives as potential therapeutic agents to enhance diabetic wound healing. This paper aims to provide an academic review of the therapeutic effects of adipose-derived stem cell-EXOs (ADSC-EXOs) in diabetic wound healing. As a cell-free therapy, exosomes (EXOs) possess a multitude of proteins and growth factors that have been shown to be advantageous in promoting wound healing and mitigating the potential risks associated with stem cell therapy. By examining the current knowledge on ADSC-EXOs, this review seeks to offer insights and guidance for the potential application of EXOs in the treatment of diabetic wounds.

Fibrous metamorphosis A glimpse into hypertrophic scarring

Hypertrophic scar is an abberation of normal wound healing. It developes as a result of hypertrophy of mature fibroblast in hypertrophic scar.

In Situ Forming Bioartificial Hydrogels with ROS Scavenging Capability Induced by Gallic Acid Release with Potential in Chronic Skin Wound Treatment.

In normal chronic wound healing pathways, the presence of strong and persistent inflammation states characterized by high Reactive Oxygen Species (ROS) concentrations is one of the major concerns hindering tissue regeneration. The administration of different ROS scavengers has been investigated over the years, but their effectiveness has been strongly limited by their short half-life caused by chronic wound environmental conditions. This work aimed at overcoming this criticism by formulating bioartificial hydrogels able to preserve the functionalities of the encapsulated scavenger (i.e., gallic acid-GA) and expand its therapeutic window. To this purpose, an amphiphilic poly(ether urethane) exposing -NH groups (4.5 × 1020 units/gpolymer) was first synthesized and blended with a low molecular weight hyaluronic acid. The role exerted by the solvent on system gelation mechanism and swelling capability was first studied, evidencing superior thermo-responsiveness for formulations prepared in saline solution compared to double demineralized water (ddH2O). Nevertheless, drug-loaded hydrogels were prepared in ddH2O as the best compromise to preserve GA from degradation while retaining gelation potential. GA was released with a controlled and sustained profile up to 48 h and retained its scavenger capability against hydroxyl, superoxide and 1'-diphenyl-2-picrylhydrazyl radicals at each tested time point. Moreover, the same GA amounts were able to significantly reduce intracellular ROS concentration upon oxidative stress induction. Lastly, the system was highly cytocompatible according to ISO regulation and GA-enriched extracts did not induce NIH-3T3 morphology changes.

Clinical Evaluation of Jalaukavacharana (Medicinal Leech Therapy) in Non-Healing Ulcer

Chronic non-healing ulcers are those that do not heal within three months or often remain in the inflammatory stage for too long and may never heal or may take years. Some wounds heal easily by body’s self-healing mechanism and some poses challenge to normal wound healing and does not heal in time and becomes a matter of concern for the physicians. Leech therapy proved to be a better treatment option by benefits of its salivary constituents in wound healing. It is an ancient way of treating such complicated disorders mentioned in different texts. A patient came at Shalya Tantra OPD with ulcer on posterior aspect of right ankle joint above the heel which was not healing since 6 months even on daily antiseptic dressings. Patient gave h/o immobilization for 2 months following ORIF of same joint 7 months back. During immobilization, after 1month of ORIF, patient developed ulcer at posterior aspect of Rt. Ankle above heel. Leech was applied at wound site twice weekly initially followed by once weekly then once in 15 days along with antiseptic dressing daily. The ulcer started showing signs of healing within three sittings and completely healed by 4 months. This study was carried out in Department of Shalya Tantra, Rajiv Gandhi govt. Post Graduate Ayurvedic college and Hospital, Paprola.

A korszerű sebkezelés lehetőségei

Wound healing is a complex biochemical process involving many cell types. Normal wound healing takes 5–14 days. If the process is disturbed, prolonged wound healing occurs for a number of reasons. Correct diagnosis is important before treatment and complex treatment should be carried out accordingly, which in most cases involves a combination of appropriate systemic and top ical therapy. There are differet methods of topical treatment, which should be chosen according to the characteristics of the wound. This article summarises the treatment options available in the different stages of wound healing.

Macrophage cell morphology-imprinted substrates can modulate mesenchymal stem cell behaviors and macrophage M1/M2 polarization for wound healing applications.

Mesenchymal stem cells and macrophages (MQ) are two very important cells involved in the normal wound healing process. It is well understood that topological cues and mechanical factors can lead to different responses in stem cells and MQ by influencing their shape, cytoskeleton proliferation, migration, and differentiation, which play an essential role in the success or failure of biomaterial implantation and more importantly wound healing. On the other hand, the polarization of MQ from proinflammatory (M1) to prohealing (M2) phenotypes has a critical role in the acceleration of wound healing. In this study, the morphology of different MQ subtypes (M0, M1, and M2) was imprinted on a silicon surface (polydimethylsiloxane [PDMS]) to prepare a nano-topography cell-imprinted substrate with the ability to induce anti-inflammatory effects on the mouse adipose-derived stem cells (ADSCs) and RAW264.7 monocyte cell line (MO). The gene expression profiles and flow cytometry of MQ revealed that the cell shape microstructure promoted the MQ phenotypes according to the specific shape of each pattern. The ELISA results were in agreement with the gene expression profiles. The ADSCs on the patterned PDMS exhibited remarkably different shapes from no-patterned PDMS. The MOs grown on M2 morphological patterns showed a significant increase in expression and section of anti-inflammatory cytokine compared with M0 and M1 patterns. The ADSCs homing in niches heavily deformed the cytoskeletal, which is probably why the gene expression and phenotype unexpectedly changed. In conclusion, wound dressings with M2 cell morphology-induced surfaces are suggested as excellent anti-inflammatory and antiscarring dressings.

Glycosaminoglycans: Roles in wound healing, formation of corneal constructs and synthetic corneas

Maintaining the clarity of the cornea is essential for vision, and is achieved through an exquisite array of collagen fibrils and proteoglycans in the corneal stroma. Alterations in the identity and modifications of the glycosaminoglycans (GAGs) are seen both throughout the normal wound healing process and in pathological conditions resulting in corneal opacity. Understanding these changes has been essential for the development of corneal prostheses and corneal reconstruction. The goal of this review article is to summarize and consolidate research in the alterations seen in glycosaminoglycans in injured and hypoxic states, address the role of proteins that can regulate glycosaminoglycans in the corneal wound healing process, and apply these findings to the context of corneal restoration through reconstruction or the insertion of synthetic devices.

Ablative Fractional CO2 Laser with or without Low Dose Isotretinoin in Treatment of Acne Scars: A Comparative Study

Abstract Background Acne scarring is one of the most common sequelae of acne vulgaris. The severity of acne scars correlates with acne duration, severity and delay in treatment of acne as well as positive family history. Patients who have acne scars frequently seek treatment options to improve appearance and quality of life. Aim of the Study The aim of this study was to assess the safety of combining low-dose isotretinoin with ablative fractional CO2 laser in patients with acne scars. Patients and Methods This study included 40 patients with different types of acne scars. There were 27 females and 13 males. The patients have divided into two groups; Group A received low-dose isotretinoin with full face AF Co2 laser session, while Group B was treated with full face AF Co2 laser session. The age of patients ranged from 18 to 45 years old, with the mean age was 27.2± 6.9 yrs in group A and was 27.5± 6.06 yrs in group B. Results Duration of wound healing, PIH and pain were parallel in both groups with no significant difference between them. No other complications were reported as keloid formation, secondary infection, edema, milia or acneform eruption in study groups. Satisfactory results were reported in most of the patients. Conclusion Our study concluded that using low-dose isotretinoin with AF Co2 laser session safe procedure with normal wound healing and no keloid or hypertrophic scars formation.

The Histone Methyltransferase Whsc1 Regulates Tgfb-driven Macrophage to Myofibroblast Transition During Normal Wound Healing

The Histone Methyltransferase Whsc1 Regulates Tgfb-driven Macrophage to Myofibroblast Transition During Normal Wound Healing

Dynamic 3D genome reorganization during senescence: defining cell states through chromatin.

Cellular senescence, a cell state characterized by growth arrest and insensitivity to growth stimulatory hormones, is accompanied by a massive change in chromatin organization. Senescence can be induced by a range of physiological signals and pathological stresses and was originally thought to be an irreversible state, implicated in normal development, wound healing, tumor suppression and aging. Recently cellular senescence was shown to be reversible in some cases, with exit being triggered by the modulation of the cell's transcriptional program by the four Yamanaka factors, the suppression of p53 or H3K9me3, PDK1, and/or depletion of AP-1. Coincident with senescence reversal are changes in chromatin organization, most notably the loss of senescence-associated heterochromatin foci (SAHF) found in oncogene-induced senescence. In addition to fixed-cell imaging, chromatin conformation capture and multi-omics have been used to examine chromatin reorganization at different spatial resolutions during senescence. They identify determinants of SAHF formation and other key features that differentiate distinct types of senescence. Not surprisingly, multiple factors, including the time of induction, the type of stress experienced, and the type of cell involved, influence the global reorganization of chromatin in senescence. Here we discuss how changes in the three-dimensional organization of the genome contribute to the regulation of transcription at different stages of senescence. In particular, the distinct contributions of heterochromatin- and lamina-mediated interactions, changes in gene expression, and other cellular control mechanisms are discussed. We propose that high-resolution temporal and spatial analyses of the chromatin landscape during senescence will identify early markers of the different senescence states to help guide clinical diagnosis.

The dichotomy of dermal fillers: when does the biostimulatory response become one of regeneration versus one of replacement?

Many dermal fillers are classified as biostimulatory, meaning they stimulate the dermis to create new collagen, elastin, and other components of the extracellular matrix. Normal wound healing is also a biostimulatory process. It can be one of tissue replacement with scar formation, or one of true regenerative healing with functional restoration of the tissue. Dermal fillers can stimulate both types of healing, but to different degrees. This paper reviews this mechanism, exploring why some fillers seem to favour replacement, and some true regeneration. The patient's and the filler's propensity for late inflammatory reactions and their relationship to the biostimulatory characteristics of the product are examined as well.