Chronic Diabetic Ulcers Research Articles

Photobiomodulation studies on diabetic wound healing: An insight into the inflammatory pathway in diabetic wound healing.

Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

High glucose combined with lipopolysaccharide stimulation inhibits cell proliferation and migration of human HaCaT keratinocytes by impacting redox homeostasis and activating the polyol pathway.

High glucose level and chronic inflammation are characteristic features of diabetic cutaneous wounds. Keratinocytes make up the epidermis and play an important role in skin repair. However, metabolomic changes of keratinocytes in chronic diabetic ulcers have not been fully studied. This study used high levels of glucose combined with lipopolysaccharide to treat human HaCaT keratinocytes. Untargeted metabolomic combined with colorimetric assays were used to explore the changes of keratinocyte metabolites and related metabolic pathways caused by high glucose and lipopolysaccharide. Results demonstrated that high glucose combined with lipopolysaccharide treatment increased intracellular reactive oxygen species and impaired proliferation and migration of keratinocytes. Untargeted metabolomics analysis identified a total of 273 differential metabolites. Redox metabolism associated metabolites were largely altered. Reduced nicotinamide adenine dinucleotide, gamma-glutamylcysteine, superoxide dismutase activity and SOD2 gene expression were significantly upregulated while nicotinamide adenine dinucleotide, glutathione, glutathione peroxidase, several types of lysophosphatidylcholine, lysophosphatidylinositol, and GPR55 gene expression were downregulated. Alterations of glutathione and nicotinamide adenine dinucleotide were verified by colorimetric assays. For the first time, high glucose and LPS were observed to boost the levels of fructose, aldose reductase and sorbitol dehydrogenase of the polyol pathway in HaCaT cells. Further treatment of HaCaT with fructose leading to inhibition of cell proliferation and migration. Our data suggest high glucose combined with lipopolysaccharide significantly altered redox homeostasis associated metabolites and activate the polyol pathway in keratinocytes to impact cell proliferation and migration, providing new strategies for the treatment of chronic diabetic ulcers.

Keller and Interphalangeal Joint Resection Arthroplasties for Chronic Noncomplicated Diabetic Ulcers of the Hallux: A Systematic Review and Meta-analysis.

Surgery is often needed for resistant plantar diabetic foot ulcers (DFUs) of the big toe. For noninfected ulcers, 2 types of surgery are available: the Keller and the hallux interphalangeal joint arthroplasty (HIPJ-A) procedures. Yet, no evidence synthesis on the outcomes of these procedures has been conducted; thus, this systematic review is an attempt to fill this gap. Only studies reporting the results of Keller (or its variants) and HIPJ-A (or its variants) procedures for noncomplicated ulcers (Texas 1A/2A, or Wagner I/II) were included. Ulcers located beneath the metatarsal head were excluded. Ultimately, 11 studies were selected for inclusion and were analyzed. The primary outcome was defined as the ulcer healing frequency. The secondary outcomes were mean healing time, ulcer recurrence frequency, ulcer transfer frequency, postoperative infection rate, and revision surgery rate. The overall (combined techniques) weighted healing rate was 94% with a mean healing time of 3.1 ± 0.4 weeks. The ulcer recurrence frequency was 6%, the ulcer transfer frequency 4.5%, the postoperative infection rate 18%, and the revision surgery rate 3.8%. No significant differences were found between both techniques. When compared to standard of care, the odds ratio of ulcer healing frequency was 27.1 (95% CI 1.442-508.174, P = .01) in favor of the Keller arthroplasty with a faster healing time (P = .02). Both surgical offloading procedures are highly effective in treating chronic noncomplicated DFU of the plantar aspect of the hallux along with low complication frequencies. There is a need to fine-tune the indication in relation to the location of the plantar wound with future comparative controlled research studies with far more patients than we could include in this meta-analysis.

Infectious and Inflammatory Microenvironment Self-Adaptive Artificial Peroxisomes with Synergetic Co-Ru Pair Centers for Programmed Diabetic Ulcer Therapy.

Complex microenvironments with bacterial infection, persistent inflammation, and impaired angiogenesis are the major challenges in chronic refractory diabetic ulcers. To address this challenge, a comprehensive strategy with highly effective and integrated antimicrobial, anti-inflammatory, and accelerated angiogenesis will offer a new pathway to the rapid healing of infected diabetic ulcers. Here, inspired by the tunable reactive oxygen species (ROS) regulation properties of natural peroxisomes, this work reports the design of infectious and inflammatory microenvironments self-adaptive artificial peroxisomes with synergetic Co-Ru pair centers (APCR) for programmed diabetic ulcer therapy. Benefiting from the synergistic Co and Ru atoms, the APCR can simultaneously achieve ROS production and metabolic inhibition for bacterial sterilization in the infectious microenvironment. After disinfection, the APCR can also eliminate ROS to alleviate oxidative stress in the inflammatory microenvironment and promote wound regeneration. The data demonstrate that the APCR combines highly effective antibacterial, anti-inflammatory, and provascular regeneration capabilities, making it an efficient and safe nanomedicine for treating infectious and inflammatory diabetic foot ulcers via a programmed microenvironment self-adaptive treatment pathway. This work expects that synthesizing artificial peroxisomes with microenvironments self-adaptive and bifunctional enzyme-like ROS regulation properties will provide a promising path to construct ROS catalytic materials for treating complex diabetic ulcers, trauma, or other infection-caused diseases.

Less Invasive Off-loading Surgery of Chronic Plantar Diabetic Forefoot Ulcers: A Narrative Review

Less Invasive Off-loading Surgery of Chronic Plantar Diabetic Forefoot Ulcers: A Narrative Review

HUC-MSCs combined with platelet lysate treat diabetic chronic cutaneous ulcers in Bama miniature pig

Human umbilical cord mesenchymal stem cells (HUC-MSCs) and platelet lysate (PL) shows potential of wound healing. However, MSCs in combination with PL for wound healing is still lacking. In this study, we presented high glucose cultured wound related cells to mimic diabetic chronic ulcers (DCU) cells, wound healing indicators and the TGFβ/Smad signaling pathway were detected by PL cultured HUC-MSC supernatant (MSC-Sp) in vitro. In vivo study, diabetes was induced in pigs feeding a high-energy diet and multiple injections of streptozotocin (125 mg/kg). Chronic wounds were created on both sides of the backs of seven pigs by surgical creation and foreign body compression for eight weeks before treatment. The wounds were treated with saline control (N = 11), PL (N = 11), HUC- MSCs (N = 18, 6 × 106/mL/cm2), and PL + HUC-MSCs (N = 18, 6 × 106/mL/cm2) respectively. Tissue samples were collected to observe new collagen, neovascularization, wound healing factors, and the TGFβ/Smad signaling pathway. The resulting PL-cultured MSC-Sp promoted the proliferation of keratinocytes, fibroblasts, and vascular endothelial cells and inhibited the TGFβ1/TGFβ3 ratio, upregulated VEGF-α and PDGF-BB production by keratinocytes and fibroblasts, and downregulated the expression of CD86, IL-6, and TNF-α in RAW264.7 cells. PL + HUC-MSCs had the best wound healing rate in vivo, and promoted collagen formation, neovascularization, and inflammation, regulated the balance between IL-6/TGFβ1 and IL-6/Arg-1 and upregulated the expression of VEGF-α and TGFβ1. In summary, PL + HUC-MSCs had a better wound healing effect than HUC-MSCs or PL treatment alone by regulating the IL-6/Arg-1 and IL-6/TGFβ1 balance and upregulating TGFβ1, VEGF-α, Col1, and α-SMA.

Successful use of platelet-rich plasma as a regeneration technique for a non-healing diabetic leg ulcer with chronic osteomyelitis: A case report

Chronic diabetic leg ulcers can be challenging to manage, particularly when osteomyelitis coexists resulting in serious or even life-threatening conditions if not managed appropriately. Such cases require very long periods of treatment with several debridements, antibiotic bead implants, skin grafts or even amputations in many unfortunate cases. Despite that, conventional management appears to be inadequate with poor outcomes and a higher relapse rate. We report a case of a 26-year-old type 1 diabetic female patient presented with a history of non-healing diabetic leg ulcer complicated by chronic osteomyelitis of the left leg. Several wound debridements were performed with the application of vacuum-assisted closure, and culture-guided antibiotics were given. However, only minimal improvements were observed. Eventually, the leg was labeled as an unsalvagable limb due to poor blood supply based on an ankle-brachial index. Platelet-rich plasma (PRP) was tried showing promising results and significant improvement as confirmed by a gallium scan, which showed evidence of osteomyelitis remission. Two months later, the patient improved significantly with the ulcer healed and the osteomyelitis resolved. Autologous PRP promotes wound healing by providing necessary growth factors, reducing inflammation, and showing bactericidal activity. All efforts must be taken to preserve any limb before labeling it non-salvageable. This case report aimed to draw attention to the method that can be implemented to manage non-healing diabetic leg ulcers complicated by chronic osteomyelitis.

Near-infrared light-activatable, analgesic nanocomposite delivery system for comprehensive therapy of diabetic wounds in rats

Impaired angiogenesis, bacterial infection, persistent severe pain, exacerbated inflammation, and oxidative stress injury are intractable problems in the treatment of chronic diabetic ulcer wounds. A strategy that effectively targets all these issues has proven challenging. Herein, an in-situ sprayable nanoparticle-gel composite comprising platinum clusters (Pt) loaded-mesoporous polydopamine (MPDA) nanoparticle and QX-314-loaded fibrin gel (Pt@MPDA/QX314@Fibrin) was developed for diabetic wound analgesia and therapy. The composite shows good local analgesic effect of QX-314 mediated by near-infrared light (NIR) activation of transient receptor potential vanilloid 1 (TRPV1) channel, as well as multifunctional therapeutic effects of rapid hemostasis, anti-inflammation, antioxidation, and antibacterial properties that benefit the fast-healing of diabetic wounds. Furthermore, it demonstrates that the composite, with good biodegradability and biosafety, significantly relieved wound pain by inhibiting the expression of c-Fos in the dorsal root ganglion and the activation of glial cells in the spinal cord dorsal horn. Consequently, our designed sprayable Pt@MPDA/QX314@Fibrin composite with good biocompatibility, NIR activation of TRPV1 channel-mediated QX-314 local wound analgesia and comprehensive treatments, is promising for chronic diabetic wound therapy.

Electrical stimulation: a novel therapeutic strategy to heal biological wounds.

Electrical stimulation (ES) has emerged as a powerful therapeutic modality for enhancing biological wound healing. This non-invasive technique utilizes low-level electrical currents to promote tissue regeneration and expedite the wound healing process. ES has been shown to accelerate wound closure, reduce inflammation, enhance angiogenesis, and modulate cell migration and proliferation through various mechanisms. The principle goal of wound management is the rapid recovery of the anatomical continuity of the skin, to prevent infections from the external environment and maintain homeostasis conditions inside. ES at the wound site is a compelling strategy for skin wound repair. Several ES applications are described in medical literature like AC, DC, and PC to improve cutaneous perfusion and accelerate wound healing. This review aimed to evaluate the primary factors and provides an overview of the potential benefits and mechanisms of ES in wound healing, and its ability to stimulate cellular responses, promote tissue regeneration, and improve overall healing outcomes. We also shed light on the application of ES which holds excellent promise as an adjunct therapy for various types of wounds, including chronic wounds, diabetic ulcers, and surgical incisions.

Evaluation of the effectiveness of low-level laser therapy on proliferation of fibroblasts isolated from chronic wounds in human in vitro

Chronic wounds pose significant challenges in healthcare due to impaired healing mechanisms. Fibroblast cells play a crucial role in wound healing by orchestrating proliferation and migration. This study aimed to assess fibroblast cells derived from chronic wounds and explore the impact of low-level laser therapy (LLLT) on their growth and migration. Dermal samples from chronic pressure ulcers and diabetic ulcers were obtained from 20 patients at three sites. Fibroblasts from wound base, margins, and adjacent healing skin were isolated and characterized. Proliferation and migration capabilities of these cells were evaluated. LLLT was applied at various energy levels (2.5, 3, 3.5, 4, and 5 J/cm²) to assess its effect on cell count. Fibroblasts from chronic wounds exhibited slower proliferation and migration rates compared to normal dermal fibroblasts. Notably, LLLT intervention at different energy levels led to a significant increase in cell count, with the most pronounced effect observed at 3 J/cm². LLLT at an energy level of 3 J/cm² demonstrated a notable enhancement in fibroblast migration. These findings underscore the potential of LLLT as a therapeutic approach for chronic wounds, offering insights into its efficacy in augmenting fibroblast functions crucial for wound healing.

USE OF NANODISPERSIVE DERMATOTROPIC GEL IN THE COMPREHENSIVE TREATMENT OF TROPHIC LESIONS OF THE LOWER LIMBS IN PATIENTS WITH DIABETES MELLITUS

Given the rapid increase in the global prevalence of type 2 diabetes mellitus, an increase in the number of chronic diabetic wounds and ulcers is predicted. The problem of treating and predicting the course of trophic lesions of the lower limbs in patients with diabetes mellitus has remained unresolved until now. Successful treatment of trophic wounds in diabetic patients is a serious multidisciplinary challenge. Therefore, the development of new drugs, methods and treatment is crucial. “Cerera” Gel-Balm is an original development based on an antioxidant complex with cerium dioxide ions, providing the product with unique biological properties. The gel accelerates the regeneration processes of damaged tissues, provides antimicrobial, anti-inflammatory and anti-oedematous effects, and is effective in viral soft tissue infections. The purpose of the study was to improve the treatment outcomes of patients with diabetes mellitus and trophic ulcers by using the nanodispersive cerium dioxide-based dermatotropic gel. Methods and participants. The study was carried out at the surgery unit of Poltava Central District Clinical Hospital and the endocrinology unit the 2nd Poltava Municipal Clinical Hospital. Two distinct clinical cases have been presented where the suggested local treatment was included into the comprehensive treatment strategy. Photographic evidence of wound healing and the outcomes of laboratory and instrumental diagnostic methods are provided. Conclusions: The application of the suggested gel, following an extended but ineffective standard comprehensive treatment, has demonstrated a notable reduction in trophic ulcer healing time. It effectively safeguards against wound infections and the onset of new infections while promoting the growth of granulation tissue. This multifaceted positive impact of the gel components on trophic ulcer healing significantly enhances the patients' quality of life.

Recent Advances in Electrospun Nanofiber-Based Strategies for Diabetic Wound Healing Application.

Diabetic ulcers are the second largest complication caused by diabetes mellitus. A great number of factors, including hyperchromic inflammation, susceptible microbial infection, inferior vascularization, the large accumulation of free radicals, and other poor healing-promoting microenvironments hold back the healing process of chronic diabetic ulcer in clinics. With the increasing clinical cases of diabetic ulcers worldwide, the design and development of advanced wound dressings are urgently required to accelerate the treatment of skin wounds caused by diabetic complications. Electrospinning technology has been recognized as a simple, versatile, and cost-reasonable strategy to fabricate dressing materials composed of nanofibers, which possess excellent extracellular matrix (ECM)-mimicking morphology, structure, and biological functions. The electrospinning-based nanofibrous dressings have been widely demonstrated to promote the adhesion, migration, and proliferation of dermal fibroblasts, and further accelerate the wound healing process compared with some other dressing types like traditional cotton gauze and medical sponges, etc. Moreover, the electrospun nanofibers are commonly harvested in the structure of nonwoven-like mats, which possess small pore sizes but high porosity, resulting in great microbial barrier performance as well as excellent moisture and air permeable properties. They also serve as good carriers to load various bioactive agents and/or even living cells, which further impart the electrospinning-based dressings with predetermined biological functions and even multiple functions to significantly improve the healing outcomes of different chronic skin wounds while dramatically shortening the treatment procedure. All these outstanding characteristics have made electrospun nanofibrous dressings one of the most promising dressing candidates for the treatment of chronic diabetic ulcers. This review starts with a brief introduction to diabetic ulcer and the electrospinning process, and then provides a detailed introduction to recent advances in electrospinning-based strategies for the treatment of diabetic wounds. Importantly, the synergetic application of combining electrospinning with bioactive ingredients and/or cell therapy was highlighted. The review also discussed the advantages of hydrogel dressings by using electrospun nanofibers. At the end of the review, the challenge and prospects of electrospinning-based strategies for the treatment of diabetic wounds are discussed in depth.

Systematic review of topical interventions for the management of pain in chronic wounds.

Chronic wounds adversely affect quality of life. Pain is associated with chronic wounds, and its impact can vary according to wound aetiology, condition, and patient factors. This systematic review examined the effectiveness of topical interventions in the management chronic wound-related pain guided by PRISMA recommendations of randomised controlled trials (RCTs) where pain reduction is the primary outcome. Inclusion criteria were adults (older than 18 years) with chronic venous, arterial, diabetic, or pressure ulcers where pain has been managed through topical administration of pharmacological/nonpharmacological agents. Searches were conducted in Ovid Embase, Ovid MEDLINE, EBSCOhost, CINAHL, CENTRAL, PubMed, Web of Science, and Scopus. Studies were screened for eligibility; risk of bias and data were extracted by 2 independent assessors. Searches retrieved 10,327 titles and abstracts (7760 after deduplication). Nine full texts (1323 participants) examining ibuprofen (n = 4), morphine (n = 2), BWD + PHMB [polihexanide-containing biocellulose wound dressing] (n = 1), and EMLA (n = 2) were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Meta-analysis was not possible, but initial exploration suggests improved outcomes (reduced pain) for ibuprofen when compared with controls. Two studies involving morphine showed conflicting findings. Included studies often had small samples, and considering confounding factors (eg, comorbidities), the results should be interpreted with caution. Review of included studies suggests that topical interventions may provide pain relief in individuals with chronic wounds. Further adequately powered RCTs are recommended to assess the efficacy of topical interventions for the management of chronic wound-related pain.

Mesenchymal Stem/Stromal Cells for Therapeutic Angiogenesis.

Mesenchymal stem/stromal cells (MSCs) are known to possess medicinal properties to facilitate vascular regeneration. Recent advances in the understanding of the utilities of MSCs in physiological/pathological tissue repair and technologies in isolation, expansion, and enhancement strategies have led to the use of MSCs for vascular disease-related treatments. Various conditions, including chronic arterial occlusive disease, diabetic ulcers, and chronic wounds, cause significant morbidity in patients. Therapeutic angiogenesis by cell therapy has led to the possibilities of treatment options in promoting angiogenesis, treating chronic wounds, and improving amputation-free survival. Current perspectives on the options for the use of MSCs for therapeutic angiogenesis in vascular research and in medicine, either as a monotherapy or in combination with conventional interventions, for treating patients with peripheral artery diseases are discussed in this review.

Reduced Bioactive Microbial Products (Pathogen-Associated Molecular Patterns) Contribute to Dysregulated Immune Responses and Impaired Healing in Infected Wounds in Mice with Diabetes

Diabetic chronic ulcers are plagued with persistent nonresolving inflammation. However, diabetic wound environment early after injury suffers from inadequate inflammatory responses due to reductions in proinflammatory cytokines levels. Diabetic neutrophils have known impairments in bactericidal functions. We hypothesized that reduced bacterial killing by diabetic neutrophils, due to their bactericidal functional impairments, results in reduced bioactive bacterial products, known as pathogen-associated molecular patterns, which in turn contribute to reduced signaling through toll-like receptors, leading to inadequate production of proinflammatory cytokines in infected diabetic wound early after injury. We tested our hypothesis in db/db type 2 obese diabetic mouse wound infection model with Pseudomonas aeruginosa. Our data indicate that despite substantially higher levels of infection, toll-like receptor 4-mediated signaling is reduced in diabetic wounds early after injury owing to reduced bioactive levels of lipopolysaccharide. We further demonstrate that topical treatment with lipopolysaccharide enhances toll-like receptor 4 signaling, increases proinflammatory cytokine production, restores leukocyte trafficking, reduces infection burden, and stimulates healing in diabetic wounds. We posit that lipopolysaccharide may be a viable therapeutic option for the treatment of diabetic foot ulcers if it is applied topically after the surgical debridement process, which is intended to reset chronic ulcers into acute fresh wounds.

Telemedicine in diabetic ulcer management: A pilot study with exploration of medico-legal aspects

Background and aimsThis study aimed to evaluate the quality and efficiency of telemedicine in managing patients with chronic diabetic ulcers and provide an overview of the main medico-legal implications associated with telemedicine management of diabetic foot complications. Methods and resultsA total of 50 patients with type 2 diabetes mellitus were enrolled from a diabetic foot outpatient clinic in Cyprus between March and May 2022. Participants completed a survey concerning telemedicine services, and the demographic variables and average responses to the PACIC (Patient Assessment of Chronic Illness Care) questions were examined using descriptive analysis. The majority of patients (84%) were male, with a mean age of 60.9 ± 13.05 years. The average PACIC score was 4.42 (min. 2.7 and max. 5.0). Voice calls were the most preferred method of telemedicine delivery, accounting for 53% of all services. ConclusionTelemedicine can effectively manage chronic patients, such as those with diabetic ulcers, by reducing the burden on resources and maintaining service quality. However, healthcare professionals must be well-versed in medico-legal implications to adhere to legal and ethical guidelines, protect patient privacy, and maintain high standards of care while using telemedicine for chronic condition treatment.

Progressive Platelet Rich Fibrin tissue regeneration matrix: Description of a novel, low cost and effective method for the treatment of chronic diabetic ulcers-Pilot study.

Chronic lower limb ulcers (CLLU) are those injuries that persist for more than six weeks despite adequate care. They are relatively common; it is estimated that 10/1,000 people will develop CLLU in their lifetime. Diabetic ulcer, because of its unique pathophysiology (association between neuropathy, microangiopathy, and immune deficiency), is considered one of the most complex and difficult etiologies of CLLU for treatment. This treatment is complex, costly, and sometimes frustrating, as it is often ineffective, which worsens the quality of life of patients and makes its treatment a challenge. To describe a new method for treating diabetic CLLU and the initial results of using a new autologous tissue regeneration matrix. This is a pilot, prospective, an interventional study that used a novel protocol of autologous tissue regeneration matrix for the treatment of diabetic CLLU. Three male cases with a mean age of 54 years were included. A total of six Giant Pro PRF Membrane (GMPro) were used varying their application between one to three sessions during treatment. A total of 11 liquid phase infiltrations were performed varying their application between three and four sessions. The patients were evaluated weekly and a reduction in the wound area and scar retraction was observed during the period studied. The new tissue regeneration matrix described is an effective and low-cost method for the treatment of chronic diabetic ulcers.

Clinical and histopathological responses to bee venom phonophoresis in treating venous and diabetic ulcers: a single-blind randomized controlled trial.

Chronic venous and diabetic ulcers are hard to treat that cause patients long time of suffering as well as significant healthcare and financial costs. The conducted study was to evaluate the efficacy of bee venom (BV) phonophoresis on the healing of chronic unhealed venous and/or diabetic foot ulcers Also, to compare the healing rate of diabetic and venous ulcers. The study included 100 patients (71 males and 29 females) with an age range of 40-60 years' old who had chronic unhealed venous leg ulcers of grade I, grade II, or diabetic foot ulcers with type II diabetes mellitus. They randomly assigned into four equal groups of 25: Group A (diabetic foot ulcer study group) and group C (venous ulcer study group) who both received conservative treatment of medical ulcer care and phonophoresis with BV gel, in addition to group B (diabetic foot ulcer control group) and group D (venous ulcer control group) who both received conservative treatment of medical ulcer care and received ultrasound sessions only without BV gel. Wound surface area (WSA) and ulcer volume measurement (UVM) were used to assess the ulcer healing pre-application (P0), post-6 weeks of treatment (P1), and after 12 weeks of treatment (P2). In addition to Ki-67 immunohistochemistry was used to evaluate the cell proliferative in the granulation tissue of ulcers pre-application (P0) and after 12 weeks of treatment (P2) for all groups. This research revealed a statistical significance improvement (p ≤ 0.0) in the WSA, and UVM with no significant difference between study groups after treatment. Regarding Ki-67 immunohistochemistry showed higher post treatment values in the venous ulcer group in comparison to the diabetic foot ulcer group. Bee venom (BV) provided by phonophoresis is effective adjuvant treatment in accelerating venous and diabetic foot ulcer healing with higher proliferative effect on venous ulcer. www.ClinicalTrials.gov, identifier: NCT05285930.

Recent Tissue Engineering Approaches to Mimicking the Extracellular Matrix Structure for Skin Regeneration.

Inducing tissue regeneration in many skin defects, such as large traumatic wounds, burns, other physicochemical wounds, bedsores, and chronic diabetic ulcers, has become an important clinical issue in recent years. Cultured cell sheets and scaffolds containing growth factors are already in use but have yet to restore normal skin tissue structure and function. Many tissue engineering materials that focus on the regeneration process of living tissues have been developed for the more versatile and rapid initiation of treatment. Since the discovery that cells recognize the chemical-physical properties of their surrounding environment, there has been a great deal of work on mimicking the composition of the extracellular matrix (ECM) and its three-dimensional network structure. Approaches have used ECM constituent proteins as well as morphological processing methods, such as fiber sheets, sponges, and meshes. This review summarizes material design strategies in tissue engineering fields, ranging from the morphology of existing dressings and ECM structures to cellular-level microstructure mimicry, and explores directions for future approaches to precision skin tissue regeneration.

Current and future outlook of loaded components in hydrogel composites for the treatment of chronic diabetic ulcers.

Due to recalcitrant microangiopathy and chronic infection, traditional treatments do not easily produce satisfactory results for chronic diabetic ulcers. In recent years, due to the advantages of high biocompatibility and modifiability, an increasing number of hydrogel materials have been applied to the treatment of chronic wounds in diabetic patients. Research on composite hydrogels has received increasing attention since loading different components can greatly increase the ability of composite hydrogels to treat chronic diabetic wounds. This review summarizes and details a variety of newly loaded components currently used in hydrogel composites for the treatment of chronic diabetic ulcers, such as polymer/polysaccharides/organic chemicals, stem cells/exosomes/progenitor cells, chelating agents/metal ions, plant extracts, proteins (cytokines/peptides/enzymes) and nucleoside products, and medicines/drugs, to help researchers understand the characteristics of these components in the treatment of diabetic chronic wounds. This review also discusses a number of components that have not yet been applied but have the potential to be loaded into hydrogels, all of which play roles in the biomedical field and may become important loading components in the future. This review provides a "loading component shelf" for researchers of composite hydrogels and a theoretical basis for the future construction of "all-in-one" hydrogels.