Non-healing Wounds Research Articles

Comparative Analysis of the Efficacy of Spinal Cord Stimulation and Traditional Debridement Care in the Treatment of Ischemic Diabetic Foot Ulcers: A Retrospective Cohort Study.

Spinal cord stimulation (SCS) is an effective treatment for diabetic peripheral neuropathy. The purpose of this study was to investigate the effectiveness of SCS in the treatment of ischemic diabetic foot ulcers. In this retrospective study, the SCS group comprised 102 patients with ischemic diabetic foot who were treated with SCS for foot ulcers and nonhealing wounds due to severe lower limb ischemia. The traditional debridement care (TDC) group comprised 104 patients with ischemic diabetic foot who received only TDC. Strict screening criteria were applied. The assignment of patients to either group depended solely on their willingness to be treated with SCS. Secondary end points were transcutaneous partial pressure of oxygen (PtcO 2 ), ankle-brachial index (ABI), and color Doppler of the lower limb arteries in the feet at 6 months and 12 months after treatment. The primary end point was the amputation. The dorsal foot PtcO 2 and ABI of the patients in the SCS group were significantly improved at 6 months and 12 months postoperation ( P < .05). The therapeutic efficacy was significantly better than that of the TDC group over the same period of time ( P < .05). The degree of vasodilation of the lower limb arteries (ie, femoral, popliteal, posterior tibial, and dorsalis pedis arteries) on color Doppler was higher in the SCS group than in the TDC group ( P < .05). The odds ratios for total amputation at 6 and 12 months postoperatively in the SCS group were 0.45 (95% CI, 0.19-1.08) and 0.17 (95% CI, 0.08-0.37), respectively, compared with the TDC group. SCS improved symptoms of lower limb ischemia in ischemic diabetic feet and reduced the rate of toe amputation by increasing PtcO 2 , ABI, and arterial vasodilation in the lower limbs.

Risk Factors for Non-Healing Wounds-A Single-Centre Study.

Background: Chronic wounds present a significant clinical, social, and economic challenge. This study aimed to objectify the risk factors of healing outcomes and the duration of chronic wounds from various etiologies. Methods: Patients treated for non-healing wounds at the surgical outpatient clinic of the Olomouc Military Hospital were involved. Data from patients treated between 8/2021 and 9/2023 were selected. Patients were mostly treated as outpatients, with microbiological follow-up indicated in cases of advanced signs of inflammation. Results: There were 149 patients who met our selection criteria (the mean age was 64.4 years). Predominant causes of wounds involved diabetes (30.9%), post-trauma (25.5%), pressure ulcers (14.8%), surgical site infections (14.8%), and vascular ulcers (14.1%). Patient outcomes included wound resolution in 77.2% of patients (with a mean healing time of 110.9 days), amputation in 14.1%, and wound-related death in 8.7% of patients. Non-healing cases (amputation/death) were predicted by several local factors including an initial depth greater than 1 cm, wound secretion, inflammatory base, and a maximum wound size. Systemic factors included most strongly clinically manifested atherosclerosis and its risk factors. Of the 110 swabs performed, 103 identified at least 1 bacterial genus. The dominant risk factor for a prolonged healing duration was bacterial infection. Wounds contaminated by Proteus or Pseudomonas had prolonged healing times of 87 days (p = 0.02) and 72 days (p = 0.045), respectively. Conclusions: The early identification of local and systemic risk factors contributes to the successful resolution of chronic wounds and a reduced duration of healing.

MicroRNA-409-3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice.

Wound healing is facilitated by neoangiogenesis, a complex process that is essential to tissue repair in response to injury. MicroRNAs are small, noncoding RNAs that can regulate the wound healing process including stimulation of impaired angiogenesis that is associated with type-2 diabetes (T2D). Expression of miR-409-3p was significantly increased in the nonhealing skin wounds of patients with T2D compared to the non-wounded normal skin, and in the skin of a murine model with T2D. In response to high glucose, neutralization of miR-409-3p markedly improved EC growth and migration in human umbilical vein endothelial cells (HUVECs), promoted wound closure and angiogenesis as measured by increased CD31 in human skin organoids, while overexpression attenuated EC angiogenic responses. Bulk mRNA-Seq transcriptomic profiling revealed BTG2 as a target of miR-409-3p, where overexpression of miR-409-3p significantly decreased BTG2 mRNA and protein expression. A 3' untranslated region (3'-UTR) luciferase assay of BTG2 revealed decreased luciferase activity with overexpression of miR-409-3p, while inhibition had opposite effects. Mechanistically, in response to high glucose, miR-409-3p deficiency in ECs resulted in increased mTOR phosphorylation, meanwhile BTG-anti-proliferation factor 2 (BTG2) silencing significantly decreased mTOR phosphorylation. Endothelial-specific and tamoxifen-inducible miR-409-3p knockout mice (MiR-409IndECKO ) with hyperglycemia that underwent dorsal skin wounding showed significant improvement of wound closure, increased blood flow, granulation tissue thickness (GTT), and CD31 that correlated with increased BTG2 expression. Taken together, our results show that miR-409-3p is a critical mediator of impaired angiogenesis in diabetic skin wound healing.

The direct binding of bioactive peptide Andersonin-W1 to TLR4 expedites the healing of diabetic skin wounds

BackgroundChronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood.MethodsThe prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing.ResultsWe provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor‐κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds.ConclusionsAW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of “small” peptides in the elucidation of “big” human disease mechanisms.Graphical

Temporal and differential proteomic profile of molecular mediators associated with chronic and acute wound healing.

The underlying pathophysiology of nonhealing chronic wounds is poorly understood due to the changes occurring at the gene level and the complexity arising in their proteomic profile. Here, we elucidated the temporal and differential profile of the normal and diabetic wound-healing mediators along with their interactions and associated pathways. Skin tissues corresponding to normal and diabetic wounds were isolated at Days 0, 3, 6, and 9 representing different healing phases. Temporal gene expression was analyzed by quantitative real-timePCR. Concurrently, differential protein patterns in the wound tissues were identified by Nano LC-ESI-TOF mass spectrometry and later confirmed by Western blot analysis. Gene ontology annotation, protein-protein interaction, and protein pathway analysis were performed using DAVID, PANTHER, and STRING bioinformatics resources. Uniquely identified proteins (complement C3, amyloid beta precursor protein, and cytoplasmic linker associated protein 2) in the diabetic wound tissue implied that these proteins are involved in the pathogenesis of diabetic wound. They exhibit enhanced catalytic activity, trigger pathways linked with inflammation, and negatively regulate wound healing. However, in the normal wound tissue, axin 1, chondroitin sulfate proteoglycan 4, and sphingosine-1-phosphate receptor were identified, which are involved in proliferation, angiogenesis, and remodeling. Our findings demonstrate the correlation between elevated gene expression of tumor necrosis factor-α, interleukin(IL)-1β, and identified mediators: aryl hydrocarbon receptor nuclear translocator, 5'-aminolevulinate synthase 2, and CXC-family, that inflicted an inflammatory response by activating downstream MAPK, JAK-STAT, and NF-κB pathways. Similarly, in normal wound tissue, the upregulated IL-4 and hepatocyte growth factor levels in conjunction with the identified proteins, serine/threonine-protein kinase mTOR and peroxisome proliferator-activated receptor gamma, played a significant role in the cellular response to platelet-derived growth factor stimulus, dermal epithelialization, and cell proliferation, processes associated with the repair mechanism. Furthermore, Western blot analysis indicated elevated levels of inflammatory markers and reduced levels of proliferative and angiogenic factors in the diabetic wound.

Topical Chinese Herbal Medicine Treatment of a Non-healing Leg Wound in a Horse: A Case Report

Wound care in horses, particularly chronic non-healing lesions, pose a major medical challenge for equine practitioners and can result in considerable financial loss as well as missed training goals for owners. The lower equine limb is particularly susceptible to damage due to the lack of protective muscling and superficial synovial and tendinous structures. This paper presents the treatment of a non-healing distal leg wound in a horse by topical application of a Chinese herbal medicine decoction using a traditional Chinese veterinary medicine (TCVM) approach. The patient had sustained damage to the palmar aspect of the flexor tendons on the left thoracic limb caused by jumping off a transport vehicle. This injury was initially treated by cleaning the area, topical erythromycin antibiotic ointment and intramuscular injection of penicillin for 3 days. Over a 2-month period the initial trauma progressed to a chronic non-healing wound. Medical management of the wound was then changed to topical application of a Chinese herbal decoction which was applied 3 times daily. Over a 29-day period, this treatment encouraged normalization of the wound healing process with epithelization, tissue remodeling and normal scar formation. The clinical results achieved in this horse suggest topical treatment with Chinese herbal medicine can decrease complications and speed the healing process of chronic wounds. The use of the topical herbal formula in this case was convenient, simple to use, and cost effective.

The role of neutrophil to lymphocyte ratio with wound healing in open tibial fracture grade IIIA

Introduction: Open fractures of the tibia are challenging injuries to treat. The neutrophil-lymphocyte ratio (NLR) has been used to predict poor prognosis in various orthopedic conditions. This study aims to analyze the role of NLR in the wound healing of patients with open fractures. Methods: This is a retrospective study with data taken from all patients with grade IIIA open tibial fractures admitted to the hospital for treatment between January 2018 and June 2023. The initial NLR value and wound healing state were recapped after 6 weeks of follow-up. A statistical analysis between NLR values and wound healing state was done to measure the significance between variables. Results: There were 49 participants included in this study. Our current study found a significant difference between the mean NLR value of the healed and nonhealed wound (12.59±11.2 vs 10.46±7.9, P =0.015). The mean NLR in the healed group was significantly higher than in the nonhealed group. Calculating NLR involves dividing the absolute count of neutrophils by the total count of lymphocytes, which can be obtained through a complete blood count test. This ratio offers valuable insights into the balance between inflammatory and anti-inflammatory responses in the body. Conclusion: The NLR was significantly higher in the healed group than in the nonhealed group. Further research with higher-quality studies might be needed to prove its prognostic factor.

Hydrogel for the Treatment of Diabetic Wounds: A Comprehensive Review

Abstract: The management of chronic wounds in diabetic patients is a tough challenge, compounded by elevated amputation rates, frequent recurrence, and increased mortality rates. Nonhealing wounds in people with diabetes are produced by a combination of variables that impede the clearance of injured tissue, stimulate the formation of healthy cell populations, and increase the risk of infection. Traditional wound dressings, such as gauze, films, and bandages, focused solely on hydration and infection prev ention. However, recent scientific investigation has shifted toward advancements in wound healing treatments to overcome the constraints inherent in old methodologies. Hydrogel dressings have surfaced as a particularly enticing and promising avenue for increasing wound healing prowess in the modern medical environment, owing to their remarkable ability for moisture retention, biocompatibility profiles, and therapeutic attributes. The pathophysiology of diabetes wounds has been better studied in recent decades, and a range of functionalized hydrogel dressings have been reported with favourable outcomes, indicating that they have significant potential in healing diabetic wounds. Our approach will comprise a systematic and comprehensive evaluation of the advancements in hydrogel dressing methods related to diabetic wounds. This review presents a strong theoretical foundation for advancing hydrogel dressing technologies and offers suggestions for treating diabetic wound-related problems.

Kick-Starting Wound Healing: A Review of Pro-Healing Drugs.

Cutaneous wound healing consists of four stages: hemostasis, inflammation, proliferation/repair, and remodeling. While healthy wounds normally heal in four to six weeks, a variety of underlying medical conditions can impair the progression through the stages of wound healing, resulting in the development of chronic, non-healing wounds. Great progress has been made in developing wound dressings and improving surgical techniques, yet challenges remain in finding effective therapeutics that directly promote healing. This review examines the current understanding of the pro-healing effects of targeted pharmaceuticals, re-purposed drugs, natural products, and cell-based therapies on the various cell types present in normal and chronic wounds. Overall, despite several promising studies, there remains only one therapeutic approved by the United States Food and Drug Administration (FDA), Becaplermin, shown to significantly improve wound closure in the clinic. This highlights the need for new approaches aimed at understanding and targeting the underlying mechanisms impeding wound closure and moving the field from the management of chronic wounds towards resolving wounds.

The application of synthetic antibacterial minerals to combat topical infections: exploring a mouse model of MRSA infection

The development of new antibiotics has stalled, and novel strategies are needed as we enter the age of antibiotic resistance. Certain naturally occurring clays have been shown to be effective in killing antibiotic resistant bacteria. However, these natural clays are too variable to be used in clinical settings. Our study shows that synthetic antibacterial minerals exhibit potent antibacterial activity against topical MRSA infections and increase the rate of wound closure relative to controls. The antibacterial minerals maintain a redox cycle between Fe2+/Fe3+ and the surfaces of pyrite minerals, which act as a semiconductor and produce reactive oxygen species (ROS), while smectite minerals act as a cation exchange reservoir. Acidic conditions are maintained throughout the application of the hydrated minerals and can mitigate the alkaline pH conditions observed in chronic non-healing wounds. These results provide evidence for the strategy of ‘iron overload’ to combat antibiotic resistant infections through the maintained release of Fe2+ and generation of ROS via distinct geochemical reactions that can break the chronic wound damage cycle.

Topical Fibronectin - Novel Therapeutic Approach Has Been Formulated for Radiation Induced Skin Reactions

For a long time, radiation-induced skin reactions (RISR) or radiation ulcer (RU) were only encountered in patients undergoing radiation therapy. Nearly 90% of patients having received radiation therapy underwent moderate-to-severe skin reactions such as non-healing wounds, severely reducing patients' quality of life and adversely affecting their disease treatment. Wound healing is significantly delayed in irradiated skin. Fibronectin was the most significantly and consistently downregulated in radiation-damaged skin. From a murine model, we confirmed that radiation leads to decreased fibronectin expression in the skin as well as delayed wound healing. Topically fibronectin was found to significantly improve wound healing in irradiated skin and was associated with decreased inflammatory infiltrate and increased angiogenesis. Fibronectin treatment may be a useful adjunctive modality in the treatment of non-healing radiation wounds. Besides, this review study can be referenced for clinicians to treat RSIs to guide subsequent clinical application.

Deferoxamine Intradermal Delivery Patch for Treatment of a Beta-Thalassemia Wound.

In this study, we present the first-in-human use of topical deferoxamine (DFO) in the treatment of a beta-thalassemia wound. We elected to use DFO on a patient that suffered from a chronic nonhealing wound in the setting of beta-thalassemia. Despite approximately 55 weeks of marginal improvement in healing, this patient's wound healed completely after 21 weeks of treatment with DFO. We believe that DFO has the potential to accelerate healing in beta-thalassemia wounds through iron chelation.

Recent Applications and Evaluation of Metal Nanoparticle–Polymer Hybrids as Chronic Wound Dressings

Chronic wounds, which include venous leg ulcers, diabetic foot ulcers, and pressure ulcers, are a global health issue that affects between 1% and 2% of the developed world’s population. Chronic wound healing necessitates extensive medical intervention at costly healthcare expenses. Wound care management is mainly dependent on the discovery of new and appropriate chronic wound dressing materials, and it remains a focus of research in chronic wound care. Biocompatible metallic nanoparticle-loaded wound dressing offers a novel opportunity for effectively overcoming the inherent drawbacks of traditional wound dressing materials, particularly in overcoming nonhealing chronic wounds due to their clinical complexity, for example, wound infections, chronic irritation, and trauma, persistence of foreign body or bacterial proteins, and ischemia. In this review, we will primarily focus on the advancements in nanoparticle-based antibacterial and antioxidant wound dressing materials (e.g., hydrogels, electrospun scaffolds, sponges, and films) for the treatment of chronic wounds, which overcome the limitations of traditional dressings.

Stable closure of acute and chronic wounds and pressure ulcers and control of draining fistulas from osteomyelitis in persons with spinal cord injuries: non-interventional study of MPPT passive immunotherapy delivered via telemedicine in community care.

Micropore particle technology (MPPT) is a topical wound treatment. It is a passive immunotherapy, acting via the skin and wound microbiome without the use of antimicrobial action. In a general patient population, it removed wound infections 60% and initiated tissue regeneration 50% quicker than antibiotics and antiseptics. As MPPT supports the immune system, the aim was to confirm that MPPT is also effective in immunocompromised individuals. People with spinal cord injury (SCI) are immunodeficient due to their injury and not an underlying disease and recruit 50% fewer immune cells to an injury. The study, therefore, determined the efficacy, safety, health economics, and sustainability of MPPT in acute and chronic wounds and pressure ulcers in this patient population. Pressure ulcers in SCI persons are an orphan indication, patient variability is high, and ICH E10 excludes comparators due to ethical concerns. The study design was, therefore, a single-arm, non-interventional, observational, post-market surveillance study of MPPT for treating wounds and pressure ulcers and removing soft tissue infection in connection with draining fistulas in SCI persons. The study was based on telemedicine in community care. The study included 44 wounds. All acute and chronic grade 1-4 wounds and pressure ulcers reached stable closure. In wounds acting as fistulas draining from an underlying, primary focus of infection, e.g., osteomyelitis, MPPT removed the soft tissue infection in approx. 2.5 months and supported regeneration, considerably reducing fistula sizes. Compared to standard care, per-wound cost savings were 51 to 94% depending on wound grade and age, and substantial nursing resources were freed up. The telemedicine approach was well received by participants and supported independence and self-care. The use of antimicrobials, plastics, and synthetic polymers was essentially eliminated. MPPT did not require bed rest. The study confirmed that MPPT is safe and effective in treating acute and chronic wounds in immunocompetent and immunocompromised individuals, including wounds with antimicrobial-resistant infections. MPPT also removes soft tissue infections caused by an underlying primary focus of infection, such as osteomyelitis. Non-healing wounds currently represent an unmet clinical need. The findings suggest that a therapy acting via the microbiome without antimicrobial actions is effective.

Human keratin matrices promote wound healing by modulating skin cell expression of cytokines and growth factors.

A wide variety of biomaterials has been developed to assist in wound healing, including acellular animal and human-derived protein matrices. However, millions of patients worldwide still suffer from non-healing chronic wounds, demonstrating a need for further innovation in wound care. To address this need, a novel biomaterial, the human keratin matrix (HKM), was developed, characterised, and tested in vitro and in vivo. HKM was found to be degradation-resistant, and a proteomics analysis showed it to be greater than 99% human keratin proteins. PCR revealed adult human epidermal keratinocytes (HEKa) grown in contact with HKM showed increased gene expression of keratinocyte activations markers such as Epidermal Growth Factor (EGF). Additionally, a cytokine microarray demonstrated culture on HKM increased the release of cytokines involved in wound inflammatory modulation by both HEKa cells and adult human dermal fibroblasts (HDFa). Finally, in a murine chronic wound model, full-thickness wounds treated weekly with HKM were smaller through the healing process than those treated with human amniotic membrane (AM), bovine dermis (BD), or porcine decellularized small intestinal submucosa (SIS). HKM-treated wounds also closed significantly faster than AM- and SIS-treated wounds. These data suggest that HKM is an effective novel treatment for chronic wounds.

Monitoring the Effect of Continuous Topical Oxygen Therapy With Near-Infrared Spectroscopy: A Pilot Case Series in Wound Healing

Background. Sufficient oxygen is critical for multiple processes in wound healing. Nonhealing wounds have low tissue oxygen levels due to damaged microvasculature and comorbidities limiting tissue perfusion. Hypoxia may be reversed using continuous topical oxygen therapy (cTOT). Objective measures to identify and track hypoxic wounds and their response to adjunctive oxygen are key. Objective. To understand the effect of cTOT on recalcitrant wounds by tracking wound area and changes in tissue oxygenation using a near-infrared spectroscopy (NIRS) device. Materials and Methods. Five patients with nonhealing wounds received treatment with cTOT over 5 weeks. Routine wound measures and tissue oxygenation were recorded over that period. Results. Reductions in wound area and improvements in tissue oxygenation were seen in all 5 patients, with 3 patients healing within 5 weeks despite the previous long duration of their wounds. Trends in tissue oxygenation and relative wound surface area over the treatment period demonstrated a reduction in wound area as tissue oxygenation improved. Conclusion. This case series reinforces previous studies that cTOT is an effective, noninvasive treatment as a key adjunct to standard care in nonhealing wounds. Moreover, point-of-care tools such as the NIRS imaging device provided objective information concerning tissue oxygenation improvements, thus giving useful insights to the clinician.

Lymphangiogenesis: novel strategies to promote cutaneous wound healing.

The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.

Biocatalytic nitric oxide generating hydrogels with enhanced anti-inflammatory, cell migration, and angiogenic capabilities for wound healing applications.

Although wound healing is a normal physiological process in the human body, it is often impaired by bacterial infections, ischemia, hypoxia, and excess inflammation, which can lead to chronic and non-healing wounds. Recently, injectable hydrogels with controlled nitric oxide (NO) release behaviour have become potential wound healing therapeutic agents due to their excellent biochemical, mechanical, and biological properties. Here, we proposed novel multifunctional NO-releasing hydrogels that could regulate various wound healing processes, including hemostasis, inflammation, cell proliferation and angiogenesis. By incorporating the copper nanoparticles (NPs) in the network of dual enzymatically crosslinked gelatin hydrogels (GH/Cu), NO was in situ produced via the Cu-catalyzed decomposition of endogenous RSNOs available in the blood, thus resolving the intrinsic shortcomings of NO therapies, such as the short storage and release time, as well as the burst and uncontrollable release modes. We demonstrated that the NO-releasing gelatin hydrogels enhanced the proliferation and migration of endothelial cells, while promoting the M2 (anti-inflammatory) polarization of the macrophage. Furthermore, the effects of NO release on angiogenesis were evaluated using an in vitro tube formation assay and in ovo chicken chorioallantoic membrane (CAM) assay, which revealed that GH/Cu hydrogels could significantly facilitate neovascularization, consistent with the in vivo results. Therefore, we suggested that these hydrogel systems would significantly enhance the wound healing process through the synergistic effects of the hydrogels and NO, and hence could be used as advanced wound dressing materials.

Aging, senescence, and cutaneous wound healing-a complex relationship.

Cutaneous wound healing is a complex multi-step process that is highly controlled, ensuring efficient repair to damaged tissue and restoring tissue architecture. Multiple cell types play a critical role in wound healing, and perturbations in this can lead to non-healing wounds or scarring and fibrosis. Thus, the process is tightly regulated and controlled. Cellular senescence is defined as irreversible cell cycle arrest and is associated with various phenotypic changes and metabolic alterations and coupled to a secretory program. Its role in wound healing, at least in the acute setting, appears to help promote appropriate mechanisms leading to the complete restoration of tissue architecture. Opposing this is the role of senescence in chronic wounds where it can lead to either chronic non-healing wounds or fibrosis. Given the two opposing outcomes of wound healing in either acute or chronic settings, this has led to disparate views on the role of senescence in wound healing. This review aims to consolidate knowledge on the role of senescence and aging in wound healing, examining the nuances of the roles in the acute or chronic settings, and attempts to evaluate the modulation of this to promote efficient wound healing.

Therapeutic potential of ADSCs in diabetic wounds: a proteomics-based approach.

Diabetes mellitus (DM), a chronic metabolic disease characterized by elevated blood sugar, leads to delayed or non-healing wounds, increasing amputation risks, and placing a significant burden on patients and society. While extensive research has been conducted on adipose-derived stem cells (ADSCs) for promoting wound healing, there is a scarcity of studies focusing on diabetic wounds, particularly those employing proteomics and bioinformatics approaches. This study aimed to investigate the mechanisms by which ADSCs promote diabetic wound healing using proteomics and bioinformatics techniques. Healthy rat fat tissue was used to isolate ADSCs. A T2DM rat model with back wounds was established. The experimental group received ADSC injections around the wound, while the control group received PBS injections. Wound healing rates were documented and photographed on days 0, 3, 7, 10, and 14. On day 7, wound tissues were excised for HE and Masson's staining. Additionally, on day 7, tissues were analyzed for protein quantification using 4D-DIA, with subsequent GO and KEGG analyses for differentially expressed proteins (DEPs) and protein-protein interaction (PPI) network analysis using STRING database (String v11.5). Finally, Western blot experiments were performed on day 7 wounds to verify target proteins. In all measured days postoperatively, the wound healing rate was significantly higher in the ADSC group than in the PBS group (day 7: p < 0.001, day 10: p = 0.001, day 14: p < 0.01), except on day 3 (p > 0.05). Proteomic analysis identified 474 differentially expressed proteins, with 224 key proteins after PPI analysis (78 upregulated and 146 downregulated in the ADSC group). The main cellular locations of these proteins were "cellular anatomical entity" and "protein-containing complex", while the biological processes were "cellular processes" and "biological regulation". The primary molecular functions were "binding" and "catalytic activity", with GO enrichment focused on "Wnt-protein binding", "neural development", and "collagen-containing extracellular matrix". Further analysis of PPI network nodes using LASSO regression identified Thy1 and Wls proteins, significantly upregulated in the ADSC group, as potentially crucial targets for ADSC application in diabetic wound treatment.