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The purpose of this review is to provide verified data on the current knowledge acquired in preclinical and clinical studies regarding topically used herbal products and their active constituents (formulations and dressings) with diabetic wound healing activity. Moreover, herbal products and their active constituents used for diabetic wound infections, and various cellular and molecular mechanisms of their actions will also be described. The electronic databases were searched for articles published from 2012 to 2022. Publications with oral or systemic administration of herbal products in diabetic wound healing, published before 2012, available only as an abstract, or in languages other than English were excluded from the study. The 59 articles comparing topically used herbal products in diabetic wound healing treatment versus control treatments (placebo or active therapy) were selected. Herbal products through different mechanisms of action, including antimicrobial, anti-inflammatory, antioxidant activity, stimulation of angiogenesis, production of cytokines and growth factors, keratinocytes, and fibroblast migration and proliferation may be considered as an important support during conventional therapy or even as a substitute for synthetic drugs used for diabetic wound treatment.

Diabetic and anemia-associated diabetic wounds increase the considerable morbidity and mortality in people, as reported by clinical studies. However, no anemia-associated diabetic wound dressing materials have been developed until now. Hence, this study aimed to develop a nanocomposite scaffold composed of chitosan (CS), poly (vinyl alcohol) (PVA), and phytogenic iron oxide nanoparticles (FeO NPs), for accelerated anemia-associated diabetic wound healing. The aqueous leaves extract of Pinus densiflora (PD) was utilized for the synthesis of iron oxide nanoparticles (FeO NPs). TEM and elemental analysis confirmed smaller size PD-FeO NPs (<50 nm) synthesis with the combination of iron and oxide. In addition, in vitro biological studies displayed the moderate antioxidant, antidiabetic activities, and considerable antibacterial activity of PD-FeO NPs. Further, the different concentrations of PD-FeO NPs (0.01, 0.03, and 0.05%) incorporated CS/PVA nanocomposites sponges were developed by the freeze-drying method. The porous structured morphology and the presence of PD-FeO NPs were observed under FE-SEM. Among nanocomposite sponges, PD-FeO NPs (0.01%) incorporated CS/PVA sponges were further chosen for the in vitro wound-healing assay, based on the porous and water sorption nature. Furthermore, the in vitro wound-healing assay revealed that PD-FeO NPs (0.01%) incorporated CS/PVA has significantly increased the cell proliferation in HEK293 cells. In conclusion, the CS/PVA-PD-FeO NPs (0.01%) sponge would be recommended for diabetic wound dressing after a detailed in vivo evaluation.

As a conventional medical dressing, medical gauze does not adequately protect complex and hard-to-heal diabetic wounds and is likely to permit bacterial entry and infections. Therefore, it is necessary to develop novel dressings to promote wound healing in diabetic patients. Komagataeibacter intermedius was used to produce unmodified bacterial cellulose, which is rarely applied directly to diabetic wounds. The produced cellulose was evaluated for wound recovery rate, level of inflammation, epidermal histopathology, and antimicrobial activities in treated wounds. Diabetic mices’ wounds treated with bacterial cellulose healed 1.63 times faster than those treated with gauze; the values for the skin indicators in bacterial cellulose treated wounds were more significant than those treated with gauze. Bacterial cellulose was more effective than gauze in promoting tissue proliferation with more complete epidermal layers and the formation of compact collagen in the histological examination. Moreover, wounds treated with bacterial cellulose alone had less water and glucose content than those treated with gauze; this led to an increase of 6.82 times in antimicrobial protection, lower levels of TNF-α and IL-6 (39.6% and 83.2%), and higher levels of IL-10 (2.07 times) than in mice wounds treated with gauze. The results show that bacterial cellulose produced using K. intermedius beneficially affects diabetic wound healing and creates a hygienic microenvironment by preventing inflammation. We suggest that bacterial cellulose can replace medical gauze as a wound dressing for diabetic patients.

Diabetic wounds are characterized by chronic inflammation, vascular insufficiency, and peripheral neuropathy, which collectively disrupt the neurovascular microenvironment essential for coordinated tissue regeneration. However, strategies targeting neurovascular regeneration remain limited. Here, we developed a sprayable hydrogel sponge based on gelatin methacryloyl and methacrylamide-modified ε-poly-L-lysine (S-GPL), co-functionalized with VEGF-mimetic peptide (KLT) and BDNF-mimetic peptide (RGI). The sprayable format conforms to irregular wound geometries, while the pneumatic spraying technique generates high-pressure microbubbles that create a porous structure, thereby enhancing exudate absorption and sustained peptide release as a sponge dressing. Additionally, the incorporation of KLT and RGI facilitates the reconstruction of the neurovascular microenvironment. In vitro, KLT promoted endothelial cell maturation and cytokine secretion, whereas RGI enhanced Schwann cell activity. Notably, S-GPLKLT/RGI facilitated intercellular interactions between RSCs and HUVECs, highlighting the cellular mechanisms underlying neurovascular communication. In a full-thickness diabetic wound model in rats, the hydrogel accelerated wound closure, re-epithelialization, and matrix remodeling. These effects were accompanied by enhanced neovascularization and axonal regeneration, along with the formation of a spatially organized neurovascular niche, as evidenced by CD31+ capillaries closely aligned with PGP9.5+ nerve fibers. Building upon the intrinsic anti-inflammatory properties of S-GPL, transcriptomic and immunohistochemical analyses further revealed that S-GPLKLT/RGI treatment suppressed the IL-17 signaling pathway. However, the relationship between immunomodulation and neurovascular reconstruction warrants further investigation. Collectively, this study presents a sprayable antibacterial hydrogel that not only reconstructs the neurovascular microenvironment but also mitigates chronic inflammation, offering a clinically translatable strategy for diabetic wound management. [Display omitted] •Sprayable hydrogel sponge with mimetic peptides was developed for diabetic wound.•Spraying formed porous structure for exudate absorption and sustained peptide release.•Hydrogel enhanced neurovascular regeneration and IL-17 suppression in diabetic wounds.

Diabetic foot ulcers (DFUs) are considered one of the most severe chronic complications of diabetes and can lead to amputation in severe cases. In addition, bacterial infections in diabetic chronic wounds aggravate this scenario by threatening human health. Wound dressings made of polymer matrices with embedded metal nanoparticles can inhibit microorganism growth and promote wound healing, although the current clinical treatments for diabetic chronic wounds remain unsatisfactory. In this view, this research reports the synthesis and characterization of innovative hybrid hydrogels made of carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) chemically crosslinked by citric acid (CA) functionalized with silver nanoparticles (AgNPs) generated in situ using an eco-friendly aqueous process. The results assessed through comprehensive in vitro and in vivo assays demonstrated that these hybrid polymer hydrogels functionalized with AgNPs possess physicochemical properties, cytocompatibility, hemocompatibility, bioadhesion, antibacterial activity, and biocompatibility suitable for wound dressings to support chronic wound healing process as well as preventing and treating bacterial infections. Hence, it can be envisioned that, with further research and development, these polymer-based hybrid nanoplatforms hold great potential as an important tool for creating a new generation of smart dressings for treating chronic diabetic wounds and opportunistic bacterial infections.

Wound management remains a challenge worldwide, although there are several developed wound dressing materials for the management of acute and chronic wounds. The wound dressings that are currently used include hydrogels, films, wafers, nanofibers, foams, topical formulations, transdermal patches, sponges, and bandages. Hydrogels exhibit unique features which make them suitable wound dressings such as providing a moist environment for wound healing, exhibiting high moisture content, or creating a barrier against bacterial infections, and are suitable for the management of exuding and granulating wounds. Biopolymers have been utilized for their development due to their non-toxic, biodegradable, and biocompatible properties. Hydrogels have been prepared from biopolymers such as cellulose and chitosan by crosslinking with selected synthetic polymers resulting in improved mechanical, biological, and physicochemical properties. They were useful by accelerating wound re-epithelialization and also mimic skin structure, inducing skin regeneration. Loading antibacterial agents into them prevented bacterial invasion of wounds. This review article is focused on hydrogels formulated from two biopolymers—chitosan and cellulose—for improved wound management.

Diabetic wounds are severe injuries that are common in patients that suffer from diabetes. Most of the presently employed wound dressing scaffolds are inappropriate for treating diabetic wounds. Improper treatment of diabetic wounds usually results in amputations. The shortcomings that are related to the currently used wound dressings include poor antimicrobial properties, inability to provide moisture, weak mechanical features, poor biodegradability, and biocompatibility, etc. To overcome the poor mechanical properties, polymer-based wound dressings have been designed from the combination of biopolymers (natural polymers) (e.g., chitosan, alginate, cellulose, chitin, gelatin, etc.) and synthetic polymers (e.g., poly (vinyl alcohol), poly (lactic-co-glycolic acid), polylactide, poly-glycolic acid, polyurethanes, etc.) to produce effective hybrid scaffolds for wound management. The loading of bioactive agents or drugs into polymer-based wound dressings can result in improved therapeutic outcomes such as good antibacterial or antioxidant activity when used in the treatment of diabetic wounds. Based on the outstanding performance of polymer-based wound dressings on diabetic wounds in the pre-clinical experiments, the in vivo and in vitro therapeutic results of the wound dressing materials on the diabetic wound are hereby reviewed.

Chronic diabetic wounds are one of the main complications of diabetes, manifested by persistent inflammation, decreased epithelialization motility, and impaired wound healing. This will not only lead to the repeated hospitalization of patients, but also bear expensive hospitalization costs. In severe cases, it can lead to amputation, sepsis or death. Electrospun nanofibers membranes have the characteristics of high porosity, high specific surface area, and easy functionalization of structure, so they can be used as a safe and effective platform in the treatment of diabetic wounds and have great application potential. This article briefly reviewed the pathogenesis of chronic diabetic wounds and the types of dressings commonly used, and then reviewed the development of electrospinning technology in recent years and the advantages of electrospun nanofibers in the treatment of diabetic wounds. Finally, the reports of different types of nanofiber dressings on diabetic wounds are summarized, and the method of using multi-drug combination therapy in diabetic wounds is emphasized, which provides new ideas for the effective treatment of diabetic wounds.

The imbalance of local and systemic factors in individuals with diabetes mellitus (DM) delays, or even interrupts, the highly complex and dynamic process of wound healing, leading to diabetic foot ulceration (DFU) in 15 to 25% of cases. DFU is the leading cause of non-traumatic amputations worldwide, posing a huge threat to the well-being of individuals with DM and the healthcare system. Moreover, despite all the latest efforts, the efficient management of DFUs still remains a clinical challenge, with limited success rates in treating severe infections. Biomaterial-based wound dressings have emerged as a therapeutic strategy with rising potential to handle the tricky macro and micro wound environments of individuals with DM. Indeed, biomaterials have long been related to unique versatility, biocompatibility, biodegradability, hydrophilicity, and wound healing properties, features that make them ideal candidates for therapeutic applications. Furthermore, biomaterials may be used as a local depot of biomolecules with anti-inflammatory, pro-angiogenic, and antimicrobial properties, further promoting adequate wound healing. Accordingly, this review aims to unravel the multiple functional properties of biomaterials as promising wound dressings for chronic wound healing, and to examine how these are currently being evaluated in research and clinical settings as cutting-edge wound dressings for DFU management.

To compare recurrence rates after a 1‐year follow‐up period of healed neuroischemic diabetic foot ulcers after treatment with or without sucrose octasulfate impregnated dressing. A 1‐year prospective study with two arms was conducted between April 2021 and April 2023 on 92 patients with healed neuroischemic diabetic foot ulcers. Patients were divided into two groups; the treatment group, that includes patients healed with a sucrose octasulfate‐impregnated dressing, and the control group, which includes patients treated with other local treatments different from sucrose octasulfate‐impregnated dressings. After healing, patients were prospectively followed up during 1‐year and assessed monthly in the specialised outpatient clinics. The main outcome of the study was ulcer recurrence after wound healing within 1 year follow‐up. Secondary outcomes were minor or major amputation and all causes of death. Fifty patients in the treatment group and 42 patients in the control group were included. Fourteen (28%) patients suffered from a reulceration event in the treatment group compared to 28 (66.7%) in the control group, p < 0.001. Time to recurrence in the treatment group was 10 (16.26–2.75) and 11.50 (30.75–5.25) weeks in the control group, p = 0.464. There were no observed differences in the minor amputation rates between the two groups: 15.2% (n = 7) in the treatment group and 7.1% (n = 3) in the control group (p = 0.362). Major amputations and death outcomes were exclusively observed in the treatment group. Specifically, four major amputations (8.7%) in the treatment group were complications arising from recurring events complicated by infection during the SARS‐CoV‐2 period. Seven patients died due to complications not related with local therapy. The relative risk of recurrence was 20.18 times higher in the control group compared with those treated with octasulfate dressing (p < 0.001). Treatment with sucrose octasulfate‐impregnated dressings can decrease recurrence rates of neuroischaemic diabetic foot ulcers more effectively than neutral dressings. Besides, it may enhance the foot's clinical properties in patients with poor microcirculation, which could aid in preventing future recurrences.