Diabetes mellitus is a chronic disease that has become more prevalent worldwide because of lifestyle changes. It leads to serious complications, including increased atherosclerosis, protein glycosylation, endothelial dysfunction, and vascular denervation. These complications impair neovascularization and wound healing, resulting in delayed recovery from injuries and an elevated risk of infections. The present study aimed to investigate the effect of lipoic acid (LA) on the key mediators involved in the wound healing process, specifically CD4 + CD25 + T cell subsets, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells, T-helper-17 (Th17) cells that generate IL-17 A, glucocorticoid-induced tumor necrosis factor receptor (GITR) expressing cells, as well as cytokines such as IL-2, IL-1β, IL-6, and TNF-α and IFN-γ. These mediators play crucial roles in epidermal and dermal proliferation, hypertrophy, and cell migration.

We divided mice into 5 groups: the non-diabetic (normal control; NC), wounded non-diabetic mice (N + W), wounded diabetic mice (D + W), wounded diabetic mice treated with 50 mg/kg lipoic acid (D + W + L50) for 14 days, and wounded diabetic mice treated with 100 mg/kg lipoic acid (D + W + L100) for 14 days.

Flow cytometric analysis indicated that lipoic acid-treated mice exhibited a significant decrease in the frequency of intracellular cytokines (IL-17 A, TNF-α and IFN-γ) in CD4 + T cells, as well as a reduction in the number of GITR-expressing cells. Conversely, a significant upregulation in the number CD4+, CD25+, FOXp3 + and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells was observed in this group compared to both the normal + wounded (N + W) and diabetic + wounded (D + W) groups. Additionally, the mRNA Levels of inflammatory mediators (IL-2, IL-1β, IL-6, and TNF-α) were downregulated in lipoic acid-treated mice compared to other groups. T thereby he histological findings of diabetic skin wounds treated with lipoic acid showed well-healed surgical wounds.

These findings support the beneficial role of lipoic acid in fine-tuning the balance between anti-inflammatory and pro-inflammatory cytokines, influencing both their release and gene expression.

The current study describes the isolation of exopolysaccharide (EPS) producing lactic acid bacteria (LAB) from marine samples and testing different sugar additives with different proportions for enhanced EPS yield. The isolate MSD8 showed the most potential, yielding 200 mg/L of EPS after being cultivated at 37 °C for 48 h on de Man Rogosa and Sharpe medium (MRS) supplemented with 3% sucrose. The marine isolate MSD8 was identified as Enterococcus faecium with 99.58% probability using 16S rRNA gene sequencing. The obtained sequence was deposited in GenBank and assigned the accession number MW924065. The feature of MSD8-EPS was characterized by estimating the total carbohydrate content by UV-vis to be ~ 71%. The FTIR analysis further indicated the presence of characteristic bands of polysaccharide. The cytotoxicity of the produced MSD8-EPS was assessed using human skin fibroblasts (HSF). The IC50 was determined to be > 100 μg/mL, which signifies that MSD8-EPS is safe for skin application. The produced EPS was used to prepare a novel ointment, which was tested for wound healing ability in male albino rats. The ointment significantly (P ≤ 0.05) shortened the time needed for wound healing, as it successfully healed the wounds by 94.93% on the 7th day and completely (100%) healed the wound by the 12th day. In comparison, the control group was healed by 73.2% and 84.83%, respectively. The data confirm that the prepared ointment can safely be used for pharmaceutical wound care products.

Hippo is a signaling pathway that is evolutionarily conserved and plays critical roles in wound healing and tissue regeneration. Disruption of the transcriptional activity of both Hippo-associated factors, the yes-associated protein (YAP), and the transcriptional co-activator with PDZ binding motif (TAZ) has been associated with cardiovascular diseases, fibrosis, and cancer. This makes the Hippo pathway an appealing target for therapeutic interventions.

Prior research has indicated that medical gas plasma promotes wound healing by delivering a combination of reactive species directly to the affected areas. However, the involvement of YAP/TAZ and other signaling pathways in diabetic wound healing remains unexplored.

To this extent, ear wounds were generated and treated with gas plasma in streptozotocin (STZ)-induced diabetic mice. Transcriptome profiling at two wound healing stages (days 9 and 20 post-wounding) was performed in female and male mice. Additionally, we employed gene and protein expression analyses, utilizing immunohistological and -chemical staining of various targets as well as quantitative PCR and Western blot analysis.

Gas plasma treatment accelerated healing by increasing re-epithelialization and modifying extracellular matrix components. Transcriptomic profiling charting the major alterations in gene expression following plasma treatment was followed by a validation of several targets using transcriptional and translational quantification as well as localization analyses.

Our study evaluated the cellular regulation of essential targets of the Hippo and related pathways such as YAP/TAZ, β-catenin, tumor growth factor β, and oxidative stress signaling after plasma treatment. The activation of genes, pathways, and their regulators is an attractive therapeutic aim for a therapeutic intervention in dermal skin repair in diabetic diseases using medical gas plasmas.

Diabetic wounds are common in patients with type 2 diabetes; they are ischemic and inflammatory, and difficult to heal without intervention. Hyperbaric oxygen therapy (HBOT) is a standard treatment, but its effectiveness is limited to a subset of the aging population. Senescent fibroblasts, a hallmark of aging, impair wound healing, and senolytic drugs, like quercetin (Q), which target senescent cells, may improve healing. In this study, we developed a mathematical model that defines biological aging through two parameters, η and [Formula: see text], that decline with age. These parameters reflect the biological age of an individual, where η represents fibroblast proliferation and [Formula: see text] represents the production of the angiogenetic protein VEGF. Our model predicts that treatment with only HBOT achieves wound closure, within normal expectable time, for patients with a limited subset pairs of [Formula: see text], and this subset is increased to a larger subset by combining Q with HBOT. The two subsets of [Formula: see text] are determined explicitly by simulations of the model. To make these results applicable in clinical setting, one will have to relate the aging parameters η and [Formula: see text] to tangible marks of biological-aging factors.

Chronic wounds are often afflicted with persistent infection, excessive exudate accumulation, and delayed healing, leading to prolonged hospitalization. Excess moisture overhydrates the wound, promotes infection, and causes edema. Peri-wound skin may develop rashes, immersion injuries, and epidermal detachment. Nutrient-rich exudates foster microbial growth, increasing the infection risk. High bacterial loads lead to crust formation, continuous leakage, and foul odor, further complicating healing. To address this challenge, we developed a 3D printed amnion-based hybrid dressing comprising a regenerative layer integrated with a laminated silver-embedded polyurethane foam layer for partial and full thickness (thickness 0.12 mm-4 mm) infected wounds and burns. This dressing can suffice the varied clinical requirements of wound management by augmenting tissue regeneration, reducing bacterial load, and managing wound exudate. Human amnion was processed through decellularization and lyopreservation. Key angiogenic growth factors VEGF-A (54.12 ± 2.31 pg/mg) and PDGF-BB (3.760 ± 0.14 pg/mg) were quantified. Long-term in vitro cell viability was assessed for 20 days (as per ISO 10993-5 standards). Bioink was formulated using cryo-milled amnion particles and excipients optimized through rheology. Hybrid dressing was developed using an extrusion-based 3D printer, layering the amnion bioink onto the physical substrate, followed by lyophilization and gamma sterilization. Preclinical efficacy was assessed using a rodent Staphylococcus aureus-infected wound model, comparing the hybrid dressing to an in-house-developed amnion-mupirocin (AM) powder formulation with standard of care dressing. Both treatments demonstrated comparable wound closure rates and a significant bacterial load reduction. However, hybrid dressing offered superior healed tissue quality, increased CD31 expression, and improved neovascularization compared to AM powder treatment with a temporally regulated CD31 expression pattern mirroring the natural healing progression. This can be attributed to the hybrid construct of the dressing that provides effective exudate management, preventing its accumulation that could otherwise hinder angiogenesis, along with replenishment of wound bed with regenerative factors, aiding in mimicking the natural healing cascades.

Bacterial cellulose (BC) is a natural fiber membrane and has been applied in many biomedical applications. Herein, it was used as the main scaffold to prepare wound dressings for treating diabetic skin wounds. Polypyrrole (PPy) was first synthesized by in situ oxidative polymerization within BC membrane and applied as a photothermal agent, followed by coating with chitosan (CS) to improve the biocompatibility and antibacterial properties. SEM pictures revealed sub-micron PPy particles ranging from 100 to 200 nm were formed and attached to the BC fibrils, whereas CS formed a thin, porous layer on the surface. FTIR analysis showed that there was hydrogen bonding between BC, PPy and CS components. The crystalline structure of BC was maintained yet with decreased crystallinity by addition of PPy and CS. The water absorption capability and water vapor transmission rate decreased by PPy incorporation owing to its hydrophobic nature, but they were regained by addition of hydrophilic CS. The prepared BC/PPy/CS membrane was biocompatible toward L929 cells and maintained hemocompatibility. Additionally, both PPy and CS contributed to the antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, while they demonstrated a potential for synergistic antibacterial effects when combined. Finally, the near-infrared (NIR)-driven photothermal-hyperthermic effects by PPy on lesions upregulated heat-shock protein (HSP) expression and anti-inflammatory properties by CS boosted restoration of diabetic wounds in vivo without the addition of any antibiotics or anti-inflammatory drugs. The results thus support using the BC/PPy/CS membrane for diabetic wound regeneration.

A myriad of physical, psychosocial and environmental sequelae are associated with limb loss. However, there is a paucity of empirical South African data, which focusses on these sequelae, how they interface with the amputee's quality of life as well as the challenges they experience following amputation.

This study sought to explore the biopsychosocial effects of amputation and how it affected the quality of life of transtibial amputees.

A qualitative approach guided this study. Data were collected using one-on-one interviews with 14 unilateral transtibial amputees. Data were analysed thematically.

Five broad themes emerged from the inquiry, which captured amputees' experiences of phantom limb pain, body image disturbances and their challenges related to adapting to daily activities. Participants also expressed the salience of familial support as well as the importance of psychological interventions to cope.

The findings suggested that support networks and professional psychological intervention are imperative in facilitating successful adjustment to the amputation experience. Raising awareness of limb loss, in both rural and urban settings, may help reduce the stigma attached to it.

Quality of life comprises several domains, namely physical, psychological, environmental and social. However, limited local and international data exists regarding the environmental and social effects. This study brought to the fore the positive and negative effects of amputation in each domain, as well as various strategies, which facilitate successful adjustment to amputation.

Wound healing is a sophisticated and dynamic process carried out by a myriad of cellular activities that work together in a coordinated manner to effectively repair damaged tissue. It involves a cascade process involving hemostasis, inflammation, granulation, maturation, and remodeling. However, in the case of chronic wounds, owing to the delayed wound healing process, various microbes invade the wound area and produce biofilms that hinder the healing process. Owing to rapid advancements in nanotechnology, several nanomaterials with diverse formulations have been investigated for wound healing. Among them, silver nanoparticles (AgNPs) have shown excellent properties, as they have unique physiochemical properties that address the problems associated with wound healing. The antibacterial and antioxidant properties of silver greatly enhance wound-care diagnostics. The use of medicinal plants for green synthesis of AgNPs has been widely researched, with these plants serving as both reducing and stabilizing agents in the nanoparticle formation process. This review focuses on different wound types, problems related to wounds, green-synthesized AgNPs using medicinal plants, and their limitations and advantages in wound dressing formulations. This study aims to provide the scientific community with a directional view in analyzing the role and importance of green-synthesized AgNPs in wound care.

Diabetes mellitus is a prevalent chronic disease, often leading to complications, with chronic wounds being among the most challenging. Impairment of the CXCR4/CXCL12 signaling pathway, which plays a key role in cell mobilization, migration, and angiogenesis, significantly hampers the wound healing process in diabetic patients. Modulation of this pathway using CXCR4-targeted agents has shown promise in restoring wound repair capabilities. Additionally, the development of responsive hydrogels capable of adapting to external stimuli offers a powerful platform for drug delivery in chronic wound management. These hydrogels, when loaded with CXCR4 agonists or antagonists, enable controlled drug release and real-time therapeutic modulation. Integrating such hydrogels with existing wound healing strategies may provide an innovative and effective solution for overcoming the challenges associated with diabetic wound treatment.

Diabetes mellitus is a chronic disease that can disrupt physiologic wound healing. Medical gas plasma technology produces therapeutic reactive species that support wound healing.

Previous studies have shown that increasing the transcriptional activity of the redox regulator nuclear factor erythroid 2-related factor 2 (Nrf2) in diabetic models can improve insulin sensitivity, reduce blood glucose levels, and ameliorate diabetic complications. However, the therapeutic potential and mechanisms of action of gas plasma have not been addressed in this context.

Full-thickness dermal ear wounds were created in a preclinical mouse model of type II diabetes and compared with a native wild-type strain of C57BL/6 mice. First, the formation of reactive species in the plasma gas phase was determined by optical emission spectroscopy. Second, qPCR, protein expression, and inflammation analysis by cytokine secretion were performed to confirm the transcriptional results. Finally, qPCR and cytokine profiling were conducted to measure the effects of gas plasma in patient wound samples.

Repeated in vivo treatment with medical gas plasma supported wound healing, e.g., re-epithelialization, in both sexes. Gas plasma-stimulated changes in Nrf2 signaling associated with downstream targets were supported by the evidence of impaired wound healing in Nrf2 knockout mice. In addition, gas plasma treatment significantly affected inflammation by modulating local and systemic cytokine levels. In vivo, treatment of human diabetic wounds underscored the involvement of Nrf2 signaling in protecting against oxidative stress, as assessed by qPCR. The cytokine signature of human diabetic wounds outlined different response patterns among patients after a single exposure, while inflammatory mediators were consistently reduced after repeated plasma treatment.

The present finding of accelerated wound healing by the Nrf2 activator underlines the high potential of medical gas plasma therapy in non-diabetic and diabetic wound healing.

Diabetic wounds pose a substantial clinical challenge due to delayed healing, persistent inflammation, and susceptibility to infections. This study investigates the therapeutic efficacy of a chitosan-polyvinyl alcohol nanomembrane (OXY-NMAloe) plant-derived extracellular vesicles enriched with extracellular vesicles derived from Aloe barbadensis, Azadirachta indica, and Zingiber officinale. Chitosan, a natural biological macromolecule, forms the nanomembrane's matrix, contributing to its flexibility, porosity, and structural integrity, essential for maintaining optimal wound hydration and supporting tissue regeneration. In in vivo studies on streptozotocin-induced diabetic rats, OXY-NMAloe significantly accelerated wound closure by approximately 23 % compared to just 7 % in the control-treated group, even after one day. This effect was achieved by modulating pro-inflammatory cytokines, activating collagen synthesis, and restoring mitochondrial function. The membrane also inhibited matrix metalloproteinase overexpression, reducing excessive extracellular matrix degradation by ~40 % and promoting tissue regeneration. Furthermore, OXY-NMAloe demonstrated potent antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, decreasing microbial colonization and fostering a favorable healing environment. By integrating the structural properties of chitosan with the bioactivity of plant-derived extracellular vesicles, the nanomembrane offers a multifunctional therapeutic platform for accelerating tissue repair and addressing key challenges in diabetic wound management.

This study investigates the co-electrospinning of polyvinyl alcohol-chitosan (PVA-CS) with cerium oxide nanoparticles (CeNPs) and silk fibroin-collagen (SF-Col) with vitamin D3 for diabetic wound healing applications. The SEM results showed smooth, bead-free nanofiber structures. The diameters of the SF-Col and PVA-CS nanofibers ranged from 168 ± 51 nm to 1956 ± 450 nm and 211.4 ± 37.2 nm, respectively. By surface modification using fetal bovine serum (FBS), CeNPs dispersion was enhanced. The average diameter of the uniformly distributed fibers on the SF-Co-D/PVA-CS-CeNPs nanofibers was 621.4 ± 50.6 nm. The addition of CeNPs and vitamin D3 improved cytocompatibility at lower doses. The FTIR test confirmed polymer interactions. Contact angle measurements indicated increased hydrophilicity. SEM analysis demonstrated excellent adhesion and growth of L929 fibroblast cells and significant HUVEC migration on SF-Col-D/PVA-CS-CeNP mats, emphasizing their potential to support cell proliferation and tissue regeneration. Blood compatibility assays exhibited hemolysis percentages below 2 %, classifying the nanofibers as non-hemolytic. Antibacterial tests revealed significant reductions in Staphylococcus aureus and Pseudomonas aeruginosa survival, addressing infection concerns in chronic wounds. Furthermore, in vivo studies have demonstrated that the utilization of SF-Co-D/PVA-CS-CeNPs nanofibrous membrane as a dressing for full-thickness skin wounds in rats has resulted in accelerated tissue regeneration.

The regenerative potential of platelet-rich plasma (PRP) samples from patients with type 1 diabetes mellitus (DM) was studied in vitro. In a series of experiments, PRP was added to the culture medium of human dermal fibroblasts. The cells were tested for metabolic (including reactive oxygen species production), migration, and proliferative activities at several time points; growth factors and exosome levels were assessed in PRP and the medium. A lower proliferative effect, pro-oxidant properties, and toxicity were observed for PRPs from diabetic patients. Namely, treated fibroblasts showed lower metabolic activity, a lower cell viability, and a greater percentage of necrosis in culture, while their migration properties were not impaired. PRPs from diabetic patients exerted a lower stimulatory effect on growth factor secretion by dermal fibroblasts. PRPs from elderly diabetics had the greatest effects.

Hydrogels are three-dimensional structures that replicate natural tissues' extracellular matrix (ECM). They are essential for transporting exudates, gases, and moisture and facilitating cellular interactions in tissue engineering and wound healing. The choice of primary material in designing the scaffold is necessary to be paid more attention rather than common sources, including plant fibres like cotton, bamboo, and algae, as well as bacterial and marine-derived materials. Among them, cellulose-based polymers are especially valued for their biocompatibility and ability to promote wound healing. Chronic diabetic wounds pose unique treatment challenges, such as necrosis and infection risks. Consequently, a growing interest is in incorporating bioactive molecules into cellulose-based hydrogels. This article investigates how these infused hydrogels enhance the healing process in chronic diabetic wounds, examining various loading and crosslinking techniques alongside their clinical applications. It also discusses the benefits and limitations of bioactive molecules and their interactions with hydrogels to improve treatment strategies.

Fibroblast growth factor (FGF) is a broad class of secretory chemicals that act via FGF receptors (FGFR). The study aims to explore the role of a novel peptide, FAP1 (FGFR-agonistic peptide 1), in tissue regeneration and repair. It investigates whether FAP1 mimics basic fibroblast growth factor (bFGF) and accelerates wound healing both in vitro and in vivo.

In this study, a novel peptide was designed and its ability to mimic bFGF was assessed through different in vitro experiments including its effect on cell proliferation, wound healing, cell signaling including FGFR1 phosphorylation and activation of mitogen-activated protein kinases (MAPKs). Specificity was confirmed through surface plasmon resonance (SPR) analysis and co-treatment with FGFR inhibitor, erdafitinib. In vivo, the effect of FAP1 on diabetic wound healing was tested in a mouse model, examining collagen production and the migration and proliferation of keratinocytes and fibroblasts.

FAP1 specifically phosphorylated FGFR and activated MAPKs similar to bFGF. In vitro, it induced cell proliferation and accelerated wound healing. In vivo, FAP1 improved diabetic wound healing by increasing collagen production and promoting keratinocyte and fibroblast migration and proliferation. The specificity of FAP1 was confirmed through SPR.

FAP1 shows potential as a novel pharmacological alternative to natural bFGF for skin tissue regeneration and repair. Its ability to accelerate wound healing and its specificity for FGFR suggest that FAP1 could serve as a cost-effective substitute for bFGF protein in therapeutic applications.

Objectives: This study aimed to develop hesperidin solid lipid nanoparticles (HESP-SLNs) to enhance their stability, solubility, and sustained release for wound healing; further enhancement was achieved through prepared nanostructured lipid carriers (HESP-NLCs) using Tea Tree Oil (TTO) to explore their synergistic efficacy. Methods: A factorial design of 24 trials was established to evaluate the influence of lipid type (X1), lipid conc (%) (X2), surfactant type (X3), and sonication amplitude (%) (X4) of prepared HESP-SLNs on the particle size (nm) (Y1), polydispersibility index (Y2), zeta potential (Y3), and encapsulation efficiency (%) (Y4). The optimized HESP-SLNs formula was selected utilizing Design Expert® software version 13, which was additionally enhanced by preparing TTO-loaded HESP-NLCs. In vitro release, Raman spectroscopy, and transmission electron microscopy were carried out for both lipid nanoparticles. Cytotoxicity, in vivo wound-healing assessments, and skin irritancy tests were performed to evaluate the performance of TTO-incorporated HESP-NLCs compared to HESP-SLNs. Results: The optimized formula demonstrated PS (280 ± 1.35 nm), ZP (-39.4 ± 0.92 mV), PDI (0.239 ± 0.012), and EE% (88.2 ± 2.09%). NLCs enhanced Q6% release, (95.14%) vs. (79.69%), for SLNs and showed superior antimicrobial efficacy. Both lipid nanoparticles exhibited spherical morphology and compatibility between HESP and excipients. NLCs achieved the highest wound closure percentage, supported by histological analysis and inflammatory biomarker outcomes. Cytotoxicity evaluation showed 87% cell viability compared to untreated HSF cells, and the skin irritancy test confirmed the safety of NLCs. Conclusions: TTO-loaded HESP-NLCs are promising candidates exhibiting superior wound-healing capabilities, making them a potential therapeutic option for cutaneous wound management.

In the United States, chronic wounds affect more than 6.5 million people annually-a mean cost of $23,755 among neurosurgery patients. Current wound management solutions have disadvantages, including rejection, disease transmission from mammalian sources, and cultural issues prohibiting some products. Here, we describe preliminary use of xenograft tissue derived from axolotl (Ambystoma mexicanum) dermis for use in wound management after neurosurgical procedures.

Our prospective database was retrospectively searched for consecutive patients who underwent wound closures using axolotl dermis patches (NeoMatriX, NeXtGen Biologics, Alachua, FL). Patient demographics, daily alcohol and tobacco use, radiation history, operation type, and antibiotic regimens postclosure were collected. Rates of postoperative infection, wound dehiscence, and wound revision or repeated irrigation were collected for outcomes assessment.

Twenty-three patients underwent wound closure with the patches. At least 1 comorbidity related to delayed wound closure was present in included patients: obesity = 8 (34.8%), diabetes = 3 (13%), chronic obstructive pulmonary disease = 3 (13%), hypertension = 11 (47.8%), hyperlipidemia = 10 (43.5%), hypothyroidism = 3 (13%), benign prostatic hyperplasia = 3 (13%), human immunodeficiency virus = 1 (4.3%), cancer = 7 (30.4%), daily alcohol use = 4 (17.4%), and current smoking = 7 (30.4%). Wounds treated were from decompressive laminectomy, microvascular decompression, thoracolumbar instrumentation revision, and pseudoaneurysm ligation/resection in 1 (4.3%) patient each. Three (13%) patients had wounds from aneurysm clippings, 6 (26.1%) each from craniotomies and wound dehiscence treatments, and 4 (17.4%) from cranioplasties. Patches were applied for primary wound closure in 14 (60.9%) patients and secondary wound closure in 9 (39.1%) patients. Postapplication wound infection or wound dehiscence and/or revision occurred in 2 (8.7%) patients.

Axolotl dermis patches support mammalian wound management, demonstrating favorable potential in improving neurosurgical wound closure and healing and overall outcomes.

Chronic wounds are a severe complication of diabetes. Dysregulated inflammatory signalling is thought to underly the poor healing outcomes. Yet, there is little information available on the acute response following injury and its impact on healing.

Using a murine full thickness excisional wound model, the current study therefore assessed the expression of pro-inflammatory and pro-resolving lipid mediators during the early stages post injury in acute and diabetic wounds and compared the timeframe for transitioning through the phases of healing. Tissue eicosanoid (LTB4, PGE2, TxA2, MaR1, RvE1, RvD1, PD) and MMP-9 levels were assessed at 6 h post wounding using ELISAs. Wound closure, healing dynamics (histology), cellular infiltration and MPO, TNF-α expression (IHC) were assessed at 6 h, day2, day7 post wounding.

Eicosanoid expression did not differ between groups (LTB4 24-125 pg/mL, PGE2 63-177 pg/mL, TxA2 529-1184 pg/mL, MaR1 365-2052 pg/mL, RvE1 43-1157 pg/mL, RvD1 1.5-69 pg/mL, PD1 11.5-4.9 ng/mL). An inverse relationship (p < 0.05) between MMP-9 and eicosanoids were however only evident in acute and not in diabetic wounds. Diminished cellular infiltration (x5 fold) (p < 0.05) in diabetic wounds coincided with a significant delay in the expression of TNF-α (pro-inflammatory cytokine) and MPO (neutrophil marker). A significant difference in the expression of TNF-α (C 1.8 ± 0.6; DM 0.7 ± 0.1 MFI) and MPO (C 4.9 ± 1.9; DM 0.9 ± 0.4 MFI) (p < 0.05) was observed as early as 6 h post wounding, with histology parameters supporting the notion that the onset of the acute inflammatory response is delayed in diabetic wounds.

These observations imply that the immune cells are unresponsive to the initial eicosanoid expression in the diabetic wound tissue.

Successful wound healing in diabetic patients is hindered by dysregulated miRNA expression. This study aimed to investigate the abnormal expression of miRNAs in diabetic wound healing and the potential therapeutic role of modulating the miR-206/HIF-1α pathway. MicroRNA assays were used to identify differentially expressed miRNAs in diabetic wound sites and adjacent areas. In vitro models and a rat diabetic model were established to evaluate the effects of miR-206 on HIF-1α regulation and wound healing. The study revealed differential expression of miR-206 in diabetic wound tissues, its interaction with HIF-1α, and the inhibitory effect of miR-206 on cell growth under high glucose conditions. Modulating the miR-206/HIF-1α pathway using miR-206 antagomir promoted HIF-1α, CD34, and VEGF expression, ultimately enhancing diabetic wound healing.

Diabetes mellitus (DM) is a well-established risk factor for postoperative complications. Distal radius fractures (DRFs) are a common orthopedic injury and often require open reduction and internal fixation (ORIF). The rise of ORIF utilization warrants investigation into factors that may expose patients to postoperative complications following DRF ORIF.

We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for cases of DRF ORIF between 2015 and 2021. Cases were stratified into cohorts based on diabetes mellitus (DM) status. The DM cohort was further stratified into non-insulin-dependent DM (NIDDM) and insulin-dependent DM (IDDM) groups. Bivariate logistic regression was performed to compare patient demographics, comorbidities, and 30-day postoperative complications. Multivariate logistic regressions were performed to identify associations between diabetes mellitus status and postoperative complications.

A total of 27,761 cases of DRF ORIF were identified from 2015 to 2021. After exclusion criteria were applied, 25,971 cases remained, of which 2169 (8.4%) cases had DM and 23,802 (91.6%) cases were free of DM. Within the DM cohort, there were 1392 cases in the NIDDM subgroup and 777 cases in the IDDM subgroup. Relative to the cohort without diabetes, the IDDM cohort was independently associated with sepsis, septic shock, reintubation, myocardial infarction, blood transfusion, failure to wean off mechanical ventilation, readmission, and nonhome discharge.

Having IDDM was independently associated with higher rates of postoperative sepsis, septic shock, reintubation, myocardial infarction, blood transfusion, failure to wean off ventilation, readmission, and nonhome discharge when compared to the cohort without diabetes following DRF ORIF.

Level III; Retrospective cohort comparison; Prognosis study.

Apical periodontitis (AP) is an inflammatory immune response in periapical tissues caused by microbial infections. Failure of root canal treatment or delayed healing is often due to intracanal or extra-radicular bacteria. However, beyond microbial factors, the patient's systemic health can significantly influence the progression and healing of AP. Metabolic syndrome is a risk factor and it is characterized by a cluster of interconnected metabolic risk factors, including abdominal obesity, hyperlipidemia, hypertension, and hyperglycemia.

A comprehensive literature review was conducted on apical periodontitis and metabolic syndrome, and their impact on the roles of different immune cell populations.

Both AP and metabolic syndrome are inflammatory diseases that involve complex and interwoven immune responses. The affected immune cells are categorized into the innate (neutrophils, macrophages, and dendritic cells) and adaptive immune systems (T cells and B cells).

Metabolic diseases and AP are closely correlated, possibly intertwined in a two-way relationship driven by a shared dysregulated immune response.

Understanding the pathophysiology and immune mechanisms underlying the two-way relationship between metabolic syndrome and AP can help improve treatment outcomes and enhance the overall well-being of patients with endodontic disease complicated by metabolic syndrome.

Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing. Here, a functional and biocompatible wound dressing is developed to enable a controlled release of a traceable vector loaded with the antisense siRNA against MMP-9 in the wound. The dressing consists of degradable polymer nanofibers embedded with a vector nanosystem - polymer-coated fluorescent nanodiamonds optimized for the binding of siRNA and colloidal stability of nanodiamond-siRNA complexes in a physiological environment. The developed dressing is tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy, and handling. The treatment results in significant local inhibition of MMP-9 and a shortening of the wound healing time. The scar formation in treated diabetic-like mice becomes comparable with that in non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach to gene therapy of non-healing wounds.

Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.

Due to the ever-increasing rate of antibacterial resistance, the search for effective antibacterial agents has become imperative. Researchers have investigated the potential antimicrobial properties of various classes of nonantibiotic drugs. Statins are a group of antihyperlipidemic drugs with several cholesterol-independent effects, including antiinflammatory, immune-modulating, antioxidant, and antibacterial effects. In vitro and in vivo studies have demonstrated the antibacterial properties of statins against various grampositive and gram-negative bacteria. Simvastatin and atorvastatin are the most potent members of the family. Their antibacterial effect can be attributed to several direct and indirect mechanisms. Bacterial invasion, growth, and virulence are affected by statins. However, since in vitro minimum inhibitory concentrations (MICs) are significantly higher than serum concentrations at the lipid-lowering dosage, indirect mechanisms have been suggested to explain the positive clinical results, including reducing inflammation and improving immune response capacity. Further, statins have shown promising results when combined with antibiotics and other antibacterial agents, such as triazenes and silver nanoparticles. Despite this, the controversial aspects of statins have cast doubt on their efficacy as a possible solution for antibacterial resistance, and further research is required. Consequently, this review will examine in detail the current clinical and in vitro findings and controversies regarding statins' antibacterial properties and their relevance to antibacterial resistance.

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.

The challenge of healing diabetic skin wounds presents a significant hurdle in clinical practice and scientific research. In response to this pressing concern, we have developed a temperature-sensitive, in situ-forming hydrogel comprising poly(n-isopropylacrylamide166-co-n-butyl acrylate9) -poly(ethylene glycol) -poly(n-isopropylacrylamide166-co-butyl acrylate9) copolymer, denoted as PEP, in combination with zinc oxide nanoparticles, forming what we refer to as PEP-ZnO hydrogel. The antimicrobial properties of the PEP-ZnO hydrogel against methicillin-resistant Staphylococcus aureus were rigorously assessed by using the bacteriostatic banding method. In vitro evaluations encompassed examinations of hemocompatibility and biocompatibility. The study further employed a diabetic Sprague-Dawley (SD) rat whole-layer trauma model for comprehensive in vivo analyses. In vivo healing assessments revealed the potential of the PEP-ZnO hydrogel, characterized by increased collagen deposition and enhanced vascularization at the trauma site, thus significantly expediting the healing process. Collectively, these findings endorse the PEP-ZnO hydrogel as a safe and effective dressing for addressing chronic wounds in diabetic patients. This hydrogel not only holds promise for improving the quality of life for diabetic individuals grappling with chronic wounds but also represents a noteworthy advancement in wound care.

This review synthesizes the findings from 252 studies to explore the relationship between the oral pathogens associated with periodontitis, dental caries, and systemic diseases. Individuals with oral diseases, such as periodontitis, are between 1.7 and 7.5 times (average 3.3 times) more likely to develop systemic diseases or suffer adverse pregnancy outcomes, underscoring the critical connection between dental and overall health. Oral conditions such as periodontitis and dental caries represent a significant health burden, affecting 26-47% of Americans. The most important oral pathogens, ranked by publication frequency, include the herpes virus, C. albicans, S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans, P. intermedia, T. denticola, and T. forsythia. The systemic diseases and disorders linked to oral infections, ranked similarly, include cancer, respiratory, liver, bowel, fever, kidney, complications in pregnancy, cardiovascular bacteremia, diabetes, arthritis, autoimmune, bladder, dementia, lupus, and Alzheimer's diseases. Evidence supports the efficacy of dental and periodontal treatments in eliminating oral infections and reducing the severity of systemic diseases. The substantial burden that oral pathogens have on cancer, cardiovascular diseases, Alzheimer's, diabetes, and other systemic diseases poses a significant public health crisis.

The timely provision of load-bearing prostheses significantly reduces healthcare costs and lowers post-amputation mortality risk. However, current methods for assessing residuum health remain subjective, underscoring the need for standardized, evidence-based approaches incorporating physical biomarkers to evaluate residual limb healing and determine readiness for prosthetic rehabilitation.

This review aimed to identify predictive, diagnostic, and indicative physical biomarkers of healing of the tissues and structures found in the residual limbs of adults with amputation.

A scoping review was conducted following Joanna Briggs Institute (JBI) and PRISMA-ScR guidance. Searches using "biomarkers", "wound healing", and "amputation" were performed on May 6, 2023, on Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL databases. Inclusion criteria were: 1) References to physical biomarkers and healing; 2) Residuum tissue healing; 3) Clear methodology with ethical approval; 4) Published from 2017 onwards. Articles were assessed for quality (QualSyst tool) and evidence level (JBI system), and categorized by study, wound, and model type. Physical biomarkers that were repeated not just within categories, but across more than one of the study categories were reported on.

The search strategy identified 3,306 sources, 157 of which met the inclusion criteria. Histology was the most frequently repeated physical biomarker used in 64 sources, offering crucial diagnostic insights into cellular healing processes. Additional repeated indicative and predictive physical biomarkers, including ankle-brachial index, oxygenation measures, perfusion, and blood pulse and pressure measurements, were reported in 25, 19, 13, and 12 sources, respectively, providing valuable data on tissue oxygenation and vascular health.

Ultimately, adopting a multifaceted approach that integrates a diverse array of physical biomarkers (accounting for physiological factors and comorbidities known to influence healing) may substantially enhance our understanding of the healing process and inform the development of effective rehabilitation strategies for individuals undergoing amputation.

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV-Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (-8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin's antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

Jatyadi thailam, an Ayurvedic preparation, is renowned for its efficacy in diabetic wound healing and inflammation. This study aimed to validate and compare the diabetic wound-healing potential of two Jatyadi thailam formulations - Ayurvedic formulary of India Jatyadi thailam (JT-AFI) and Yogagrantha formulation of Jatyadi thailam (JT-YG), in a diabetic environment using L929 fibroblast cells in vitro.

The effects on cell survival, proliferation, migration, angiogenesis, cell cycle progression, apoptosis, ROS generation, and mitochondrial function were evaluated.

The formulations promoted cell proliferation, migration, angiogenesis, while also regulating cell cycle and apoptosis. They effectively suppressed ROS generation and modulated mitochondrial function. JT-AFI exhibited superior efficacy in accelerating diabetic wound healing compared to JT-YG.

These findings provide substantial support for the mechanistic role of Jatyadi thailam in diabetic wound healing.

Wound healing impairment in diabetes mellitus is associated with an excessive inflammatory response and defective regeneration capability with suppressed Hedgehog (Hh) signaling. The bromodomain protein BRD9, a subunit of the non-canonical BAF chromatin-remodeling complex, is critical for macrophage inflammatory response. However, whether the epigenetic drug BRD9 degrader can attenuate the sustained inflammatory state of wounds in diabetes remains unclear. Without a bona fide immune microenvironment, Hh signaling activation fails to effectively rescue the suppressed proliferative ability of dermal fibroblasts and the vascularization of endothelial cells. Therefore, a silk-based core-shell microneedle (MN) patch is proposed to dynamically modulate the wound immune microenvironment and the regeneration process. Specifically, the BRD9 degrader released from the shell of the MNs mitigated the excessive inflammatory response in the early phase. Subsequently, the positively charged Hh signaling agonist is released from the negatively charged core of the silk fibroin nanofibers and promotes the phase transition from inflammation to regeneration, including re-epithelialization, collagen deposition, and angiogenesis. These findings suggest that the programmed silk-based core-shell MN patch is an ideal therapeutic strategy for effective skin regeneration in diabetic wounds.

Wound healing, an intricate biological process, comprises orderly phases of simple biological processed including hemostasis, inflammation, angiogenesis, cell proliferation, and ECM remodeling. The regulation of the shift in these phases can be influenced by systemic or environmental conditions. Any untimely transitions between these phases can lead to chronic wounds and scarring, imposing a significant socio-economic burden on patients. Current treatment modalities are largely supportive in nature and primarily involve the prevention of infection and controlling inflammation. This often results in delayed healing and wound complications. Recent strides in regenerative medicine and tissue engineering offer innovative and patient-specific solutions. Mesenchymal stem cells (MSCs) and their secretome have gained specific prominence in this regard. Additionally, technologies like tissue nano-transfection enable in situ gene editing, a need-specific approach without the requirement of complex laboratory procedures. Innovating approaches like 3D bioprinting and ECM bioscaffolds also hold the potential to address wounds at the molecular and cellular levels. These regenerative approaches target common healing obstacles, such as hyper-inflammation thereby promoting self-recovery through crucial signaling pathway stimulation. The rationale of this review is to examine the benefits and limitations of both current and emerging technologies in wound care and to offer insights into potential advancements in the field. The shift towards such patient-centric therapies reflects a paradigmatic change in wound care strategies.

Type 2 diabetes mellitus (T2DM), responsible for most diabetes cases recorded worldwide, increases the risk of chronic wounds and amputation. Patients with T2DM appear to be more susceptible to delayed wound healing due to their treatment adherence. This review explores the specifics of polypharmacy, side effects, possible drug interactions and the importance of medication adherence for therapeutic efficacy. We discuss the effects of anti-diabetes medications on wound healing as well as the role that biofilms and microbial infections play in diabetic wounds. Inconsistent use of medications can lead to poor glycaemic control, which negatively affects the healing process of diabetic foot ulcers. Managing chronic wounds represents a substantial portion of healthcare expenditures. Biofilm-associated infections are difficult for the immune system to treat and respond inconsistently to antibiotics as these infections are slow growing and persistent. Additionally, we emphasize the critical role pharmacists play in enhancing patient adherence and optimizing diabetes treatment by offering comprehensive coverage of drugs associated with problems related to pharmacological therapy in type 2 diabetes.

The objective of this systematic review and meta-analysis is to assess the efficacy of the biodegradable temporising matrix (BTM) (NovoSorb; PolyNovo Biomaterials Pty Ltd, Port Melbourne, Victoria, Australia) in the reconstruction of complex upper extremity wounds. The authors conducted a systematic review and meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines assessing the efficacy of BTM in complex upper extremity wound reconstruction. The primary outcome measures were successful BTM integration and the proportion of wounds healed. Secondary outcomes analysed were the average time from BTM application to its integration, the proportion of wounds healed by secondary intention, graft take over BTM, as well as the incidence of infection. The rate of complications as well as scarring and outcomes in upper limb function were also evaluated. The inclusion criteria were met by 12 studies consisting of 164 complex upper extremity wounds. Successful BTM integration was reported in 92.1% (p<0.001) of cases, coupled with wound healing achieved in 90% (p<0.001) of cases overall. The average time to integration for BTM was 37.37 days (p<0.001). The average infection rate for upper extremity wounds with BTM application was 8.5% (p<0.001). Satisfactory scarring and functional outcomes were reported in the majority of the studies. The authors conclude that BTM offers good wound healing outcomes for upper extremity reconstruction. The studies analysed indicate good graft take rates and a low infection incidence; however, further prospective randomised studies are required to support the efficacy of BTM compared to other dermal matrices.

Following lower limb amputation, timely prosthetic fitting enhances mobility and quality of life. However, inconsistent definitions of surgical site healing complicate prosthesis readiness assessment and highlight the need for objective wound management measures.

This review aimed to compile definitions of healing and non-healing provided in the literature investigating biomarkers of healing of the tissues and structures found in the residual limbs of adults with amputation.

A scoping review was conducted following JBI and PRISMA-ScR guidance. Searches using "biomarkers," "wound healing," and "amputation" were performed on May 6, 2023, on Web of Science, Ovid MEDLINE, Ovid Embase, Scopus, Cochrane, PubMed, and CINAHL databases. Inclusion criteria were: 1) References to biomarkers and healing; 2) Residuum tissue healing; 3) Clear methodology with ethical approval; 4) Published from 2017 onwards. Articles were assessed for quality (QualSyst tool) and evidence level (JBI system).

Of 3,306 articles screened, 219 met the inclusion criteria and are reviewed in this article, with 77% rated strong quality. 43% of all included sources did not define healing, while the remainder used specific criteria including epithelialization (14%), wound size reduction (28%), gradings scales (3%), scarring (1%), absence of wound complications (2%), hydroxyproline levels (0.5%), no amputation (0.5%), or neovascularization (0.5%). 84% of included sources did not provide definitions of non-healing. Studies defining non-healing used criteria like wound complications (4%), the need for operative interventions (4%), or lack of wound size reduction (1%). For 10% of included sources, healing and non-healing definitions were considered not applicable given the research content. Total percentages exceed 100% for both healing and non-healing definitions because some sources used two definition classifications, such as epithelialization and wound size reduction. The findings indicate a lack of standardized definitions irrespective of study type.

This review reveals significant gaps in current definitions of healing and non-healing, often based on superficial assessments that overlook deeper tissue healing and mechanical properties essential for prosthesis use. It emphasizes the need for comprehensive definitions incorporating biomarkers and psychosocial factors to improve wound management and post-amputation recovery.

Caring for patients with hard-to-heal (chronic) wounds requires a multifaceted approach that addresses their diverse needs, which can contribute to the complexity of care. Wound care providers must have a comprehensive understanding of the patient's comorbid conditions and psychosocial issues to provide personalised and effective treatment. Key quality indicators for effective wound care involves not only selecting appropriate local wound care products, such as foam dressings, but also addressing individual patient experiences of wound-related pain, odour, itch, excessive wound drainage, and self-care needs. The purpose of this review is to inculcate the wound care practice community, research scientists and healthcare industry with a sense of accountability in order to work collaboratively in addressing these unmet care needs.

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 - time for 80% drug release - 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Background:After skin damage, a complicated set of processes occur for epidermal and dermal wound healing. This process is hindered under diabetic conditions, resulting in nonhealing diabetic ulcers. In diabetes there is an increase in inflammation and proinflammatory cytokines. Modulating cells using photobiomodulation (PBM) may have an effect on inflammation and cell viability, which are crucial for the healing of wounds. Objective: This study explored the impact of PBM in the near-infrared spectrum (830 nm; 5 J/cm2) on inflammation in diabetic wound healing. Materials and Methods: Five cell models, namely normal, wounded, diabetic, diabetic wounded, and wounded with d-galactose were used. Cell morphology and migration rate were assessed, while cellular response measures included viability (Trypan blue and adenosine triphosphate), apoptosis (annexin-V/PI), proinflammatory cytokines interleukin-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2, nuclear translocation of nuclear factor kappa B (NF-κB), and gene expression of advanced glycation end product receptor (AGER). Results: PBM resulted in increased levels of TNF-α, supported by activation of NF-κB. PBM stimulated translocation of NF-κB and upregulation of AGER. Conclusions: PBM modulates diabetic wound healing in vitro at 830 nm through stimulated NF-κB signaling activated by TNF-α.

To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats.

Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein.

There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14.

Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.

Diabetic wounds are often chronic in nature, and issues like elevated blood sugar, bacterial infections, oxidative stress and persistent inflammation impede the healing process. To ensure the appropriate healing of wounds, scaffolds should promote complete tissue regeneration in wounds, both functionally and structurally. However, the available scaffolds lack the explicit architecture and functionality that could match those of native skin, thus failing to carry out the scar-free skin regeneration in diabetic wounds. This study deals with the synthesis of a bi-layered nanofibrous scaffold mimicking the native skin architecture in terms of porosity and hydrophobic-hydrophilic gradients. In addition, herbal extracts of Aloe vera and litchi honey were added in consecutive layers to manage the high blood glucose level, inflammation, and increased ROS level associated with diabetic wounds. In vitro studies confirmed that the prepared scaffold with herbal extracts showed enhanced proliferation of skin cells with good mechanical strength, degradability, anti-bacterial and anti-diabetic properties. The scaffold also demonstrated superior wound healing in vivo with quicker scar-free wound recovery and appropriate skin regeneration, compared to conventional treatment. Altogether, the synthesized herbal extract loaded bi-layered nanofibrous scaffold can be used as a regenerative template for hard-to-heal diabetic wounds, offering a new strategy for the management of chronic wounds.

Wound management spans various techniques and materials tailored to address acute and chronic non-healing wounds, with the primary objective of achieving successful wound closure. Chronic wounds pose additional challenges, often necessitating dressings to prepare the wound bed for subsequent surgical procedures like skin grafting. Ideal dressing materials should not only expedite wound healing but also mitigate protein, electrolyte, and fluid loss while minimizing pain and infection risk. Nanotechnology has emerged as a transformative tool in wound care, revolutionizing the landscape of biomedical dressings. Its application offers remarkable efficacy in accelerating wound healing and combating bacterial infections, representing a significant advancement in wound care practices. Integration of nanotechnology into dressings has resulted in enhanced properties, including improved mechanical strength and controlled drug release, facilitating tailored therapeutic interventions. This review article comprehensively explores recent breakthroughs in wound healing therapies, with a focus on innovative medical dressings such as nano-enzymes. Additionally, the utilization of smart materials, like hydrogels and electroactive polymers, in wound dressings offers dynamic functionalities to promote tissue regeneration. Emerging concepts such as bio-fabrication, microfluidic systems, bio-responsive scaffolds, and personalized therapeutics show promise in expediting wound healing and minimizing scarring. Through an in-depth exploration of these advancements, this review aims to catalyze a paradigm shift in wound care strategies, promoting a patient-centric approach to therapeutic interventions.