Diabetic Wound Research Articles

On-demand Opto-Laser activatable nanoSilver ThermoGel for treatment of full-thickness diabetic wound in a mouse model

Patients suffering from diabetes mellitus are prone to develop diabetic wounds that are non-treatable with conventional therapies. Hence, there is an urgent need of hour to develop the therapy that will overcome the lacunas of conventional therapies. This investigation reports the Quality by Design-guided one-pot green synthesis of unique Opto-Laser activatable nanoSilver ThermoGel (OL→nSil-ThermoGel) for hyperthermia-assisted treatment of full-thickness diabetic wounds in mice models. The characterization findings confirmed the formation of spherical-shaped nanometric Opto-Laser activatable nanoSilver (30.75 ± 2.7 nm; ∆T: 37 ± 0.2 °C → 66.2 ± 0.1 °C; at 1.8 W/cm2 NIR laser density). The findings indicated acceptable in vitro cytocompatibility and significant keratinocyte migration (95.04 ± 0.07 %) activity of OL→nSil towards HaCaT cells. The rheological data of OL→nSil hybridized in situ thermoresponsive gel (OL→nSil-ThermoGel) showed the gelling temperature at 32 ± 2 °C. In vivo studies on full-thickness diabetic wounds in a Mouse model showed OL→nSil-ThermoGel accelerated wound closure (94.42 ± 1.03 %) and increased collagen synthesis, angiogenesis, and decreased inflammatory markers. Similarly, immunohistochemistry study showed significant angiogenesis and faster phenotypic switching of fibroblasts to myofibroblasts in OL→nSil-ThermoGel treated diabetic wounds. Histological evaluation revealed a marked rise in keratinocyte migration, organized collagen deposition, and early regeneration of the epithelial layer compared to the diabetic wound control. In conclusion, the OL→nSil-ThermoGel modulates the cytokines, re-epithelialization, protein expression, and growth factors, thereby improving the repair and regeneration of diabetic wounds in mice.

Quaternary ammonium grafted chitosan hydrogel with enhanced antibacterial performance as tannin acid and deferoxamine carrier to promote diabetic wound healing

The delay of diabetic wound healing puts a huge burden on the society. The key factors hindering wound healing include bacterial infection, unresolved inflammation and poorly generated blood vessels. In this paper, glycidyl trimethyl ammonium chloride (GTA) was grafted to chitosan (CS) to obtain quaternary ammonium grafted chitosan (QCS) with enhanced antibacterial performance, and then cross-linked by dialdehyde terminated poly(ethylene oxide) (PEO DA) to construct QCS/PEO DA hydrogel with tissue adhesion, biodegradation and self-healing properties. The QCS/PEO DA hydrogel is loaded with tannin acid (TA) and deferoxamine (DFO) to enhance antioxidant property and angiogenesis. At the same time, the TA and DFO loaded TA@DFO/hydrogel preserved the biocompatibility and biodegradability of chitosan. Moreover, the multifunctional hydrogel behaved excellent hemostatic properties in mice model and significantly promoted the healing efficacy of diabetic wounds. Overall, the TA@DFO/hydrogel is promising anti-infection dressing material for diabetic wound healing.

Hypoxic microenvironment promotes diabetic wound healing by polarizing macrophages to the M2 phenotype in vivo.

In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing. The 18 diabetic mice were randomly divided into three groups: a control group (n = 6), a 100µM DFO group (n = 6), and a 200µM DFO group (n = 6). Subsequently, a full-thickness wound with a diameter of 1.00cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells. In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization. The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.

A one-stop integrated natural antimicrobial microneedles with anti-inflammatory, pro-angiogenic and long-term moisturizing properties to accelerate diabetic wound healing

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds.

Suppression the glucose-induced ferroptosis in endothelial cells by 4OI-loading exosomes hydrogel for the treatment of diabetic foot ulcer

The prevalence of diabetic foot ulcer in individuals with diabetes is approximately 15%, and it is frequently accompanied by vascular dysfunction and infection. The management challenges make it the primary cause for amputation; however, the underlying mechanisms remain poorly understood, thereby impeding the advancement of novel wound dressings and medication. Herein, single-cell sequencing analysis revealed that ferroptosis induced by high glucose levels in vascular endothelial cells (VECs) represents a significant molecular pathological feature in diabetic foot ulcer (DFU) tissue. Furthermore, 4-Octyl itaconate (4OI) exhibited a pronounced protective effect against VECs injury induced by high glucose (HG), and its underlying molecular mechanisms involve the mitigation of HG-induced reactive oxygen species (ROS) injury and ferroptosis in VECs through the regulation Keap1/Nrf2/GPX4. For enhanced application, incubation at 37℃ was used to load 4OI into exosomes, which were subsequently encapsulated within an Alg-DA/GelMA-based hydrogel matrix. Remarkably, the utilization of 4OI-Exo-Gel not only expedited wound healing but also significantly improved the overall quality of healing in DFU. In conclusion, these findings not only demonstrate, for the first time, the remarkable ability of 4OI to enhance diabetic wound healing by mitigating VECs ferroptosis induced by HG, but also provide evidence for the potential clinical translation of a 4OI-loaded exosomes hydrogel in diabetic wound therapy.

Effects of continuous negative pressure suction combined with autologous platelet-rich gel on the levels of CRP, IL-6, wound healing and length of stay in clients with diabetic foot

ObjectiveContinuous passive pressure suction and APG gel therapy effect diabetic foot IL-6, CRP, wound healing, and hospitalization. MethodsClinicopathological data from 102 diabetic foot ulcer patients treated at our institution between March 2018 and May 2022 was examined. Tables generated 51 joint and controlling teams randomly. The observation team received passive pressure suction and APG gel whereas the controlled team received conventional treatment. Teams monitored therapy outcomes, adverse responses, wound healing, hospital stay, and costs. Both teams compared blood uric acid, cystatin C, homocysteine, and serum IL-6, IL-10, and CRP before and after medication. ResultsThe joint team had higher hospitalization costs, shorter stays, and faster wound healing than the controlled team. Diaparity was significant (P < 0.05). The united team worked 100 %, unlike the controlling team. This difference was significant (P < 0.05). Both teams showed significant decreases in CRP, IL-6, and IL-10 levels after therapy (P < 0.05). After therapy, both the combined and controlled teams had substantial differences in blood CRP, IL-6, and IL-10 levels (P < 0.05). Both teams had significantly decreased uric acid, cystatin C, and homocysteine after treatment. The combined team showed significantly decreased uric acid, cystatin C, homocysteine levels following therapy compared to the control team (P < 0.05). ConclusionThe joint team experienced considerably fewer adverse events (3.92 % vs. 17.65 %) than the controls team (P < 0.05). Permanent passive pressure suction and APG gel therapy lower inflammatory response, blood uric acid, cystatin C, and homocysteine, speeding wound healing, reducing side effects.

Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

A nature-based solution for regulating the inflammatory phase of diabetic wound healing using a cold atmospheric plasma

A nature-based solution for regulating the inflammatory phase of diabetic wound healing using a cold atmospheric plasma

Functionalised Sodium-Carboxymethylcellulose-Collagen Bioactive Bilayer as an Acellular Skin Substitute for Future Use in Diabetic Wound Management: The Evaluation of Physicochemical, Cell Viability, and Antibacterial Effects.

The wound healing mechanism is dynamic and well-orchestrated; yet, it is a complicated process. The hallmark of wound healing is to promote wound regeneration in less time without invading skin pathogens at the injury site. This study developed a sodium-carboxymethylcellulose (Na-CMC) bilayer scaffold that was later integrated with silver nanoparticles/graphene quantum dot nanoparticles (AgNPs/GQDs) as an acellular skin substitute for future use in diabetic wounds. The bilayer scaffold was prepared by layering the Na-CMC gauze onto the ovine tendon collagen type 1 (OTC-1). The bilayer scaffold was post-crosslinked with 0.1% (w/v) genipin (GNP) as a natural crosslinking agent. The physical and chemical characteristics of the bilayer scaffold were evaluated. The results demonstrate that crosslinked (CL) groups exhibited a high-water absorption capacity (>1000%) and an ideal water vapour evaporation rate (2000 g/m2 h) with a lower biodegradation rate and good hydrophilicity, compression, resilience, and porosity than the non-crosslinked (NC) groups. The minimum inhibitory concentration (MIC) of AgNPs/GQDs presented some bactericidal effects against Gram-positive and Gram-negative bacteria. The cytotoxicity tests on bilayer scaffolds demonstrated good cell viability for human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Therefore, the Na-CMC bilayer scaffold could be a potential candidate for future diabetic wound care.

Identifying the molecular mechanisms of action of wound healing properties of Mathan tailam and Mahamegarajanga tailam in Wistar albino rats: Evidence through IL-10/VEGF/TNF-α signalling pathways

The Siddha system of medicine (SSM) is the oldest medical science practised in the ancient period of the southern part of India and Sri Lanka. Many formulations were described for wound healing in the SSM, with specific diagnostic differentiation in the Siddha literature. Most preparations for wound healing were available in the form of oil-based formulations, especially for external usage. Mathan tailam (MT) and Mahamegarajanga tailam (MMRT) have been used by Siddha physicians and traditional practitioners to treat wounds. Mathan tailam is a popular regimen for skin lacerations, burns, skin infections, diabetic wounds, and dermatitis. Mahamegarajanga tailam has long been used by traditional vaidyars to treat cuts and burns. Both MT and MMRT are clinically well-appreciated drugs for wound healing and need to be studied for their mechanisms of action for scientific documentation. In an in vivo study on albino rats -excisional wound model, the histopathological changes, histo-immune response, biomarker analysis, and mRNA expression were studied and analysed. Wounds treated with MT and MMRT healed faster (p < 0.05) than the untreated group (CNT). Histological investigation showed rapid re-epithelialization, dense collagen deposition, increased enzymatic antioxidant activities and decreased lipid peroxidation in the MT and MMRT groups. mRNA expression reveals MT and MMRT-treated tissues able to induce convergent cell motility in wound space. Our study for the first time provides strong in vivo experimental evidence that Mathan tailam and Mahamegarajanga tailam play a crucial role in promoting skin tissue wound healing through IL-6/VEGF/TNF-α mediated mechanisms. Traditional practices continue to teach us valuable lessons, as seen by their continuous use in their locality for years.

Structurally Oriented Carbon Dots as ROS Nanomodulators for Dynamic Chronic Inflammation and Infection Elimination.

The selective elimination of cytotoxic ROS while retaining essential ones is pivotal in the management of chronic inflammation. Co-occurring bacterial infection further complicates the conditions, necessitating precision and an efficacious treatment strategy. Herein, the dynamic ROS nanomodulators are rationally constructed through regulating the surface states of herbal carbon dots (CDs) for on-demand inflammation or infection elimination. The phenolic OH containing CDs derived from honeysuckle (HOCD) and dandelion (DACD) demonstrated appropriate redox potentials, ensuring their ability to scavenge cytotoxic ROS such as ·OH and ONOO-, while invalidity toward essential ones such as O2·-, H2O2, and NO. This enables efficient treatment of chronic inflammation without affecting essential ROS signal pathways. The surface C-N/C═N of CDs derived from taxus leaves (TACD) and DACD renders them with suitable band structures, facilitating absorption in the red region and efficient generation of O2·- upon light irradiation for sterilization. Specifically, the facilely prepared DACD demonstrates fascinating dynamic ROS modulating ability, making it highly suitable for addressing concurrent chronic inflammation and infection, such as diabetic wound infection. This dynamic ROS regulation strategy facilitates the realization of the precise and efficient treatment of chronic inflammation and infection with minimal side effects, holding immense potential for clinical practice.

Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift

AbstractDiabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.

Oxygen-Propelled Dual-Modular Microneedles with Dopamine-Enhanced RNA Delivery for Regulating Each Stage of Diabetic Wounds.

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.

Advancing self‐healing soy protein hydrogel with dynamic Schiff base and metal‐ligand bonds for diabetic chronic wound recovery

AbstractTo address the unique challenges of diabetic wound healing, wound dressings, particularly multifunctional hydrogels have garnered considerable interest. For the first time, a novel environmentally friendly soy protein‐based hydrogel is developed to accelerate the healing of diabetic chronic wounds. Specifically, this hydrogel framework is in direct formation through the dynamic Schiff base between oxidized guar gum and epigallocatechin‐3‐gallate (EGCG)‐modified soy protein isolate. Meantime, the addition of Ag+ enhances the cross‐linking of the hydrogel network by forming metal‐ligand bonds with the catechol groups in EGCG. Interestingly, the stretchability (up to 380%), swelling, and rheology properties of the hydrogel can be controlled by fine‐tuning the density of metal‐ligand bonds, endowing them with a high potential for precise matching. Additionally, various dynamic bonds endow hydrogel with excellent self‐healing ability, adhesiveness, and injectability. This hydrogel also exhibits good antibacterial properties, biocompatibility, and cell migration capabilities. Both in vivo and in vitro experiments demonstrated the outstanding anti‐inflammatory capacity of the hydrogel and its ability to modulate macrophage polarization. Consequently, the hydrogel has proven effective in promoting wound healing in a diabetic full‐thickness wound model through enhanced angiogenesis and collagen deposition. This eco‐friendly plant protein hydrogel offers a sustainable solution for wound care and environmental protection.

Elastic Nanofibrous Dressings with Mesenchymal Stem Cell-Recruiting and Protecting Characteristics for Promoting Diabetic Wound Healing.

Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.

Cuttlefish ink-derived melanin nanoparticle-embedded tremella fuciformis polysaccharide hydrogels for the treatment of MRSA-infected diabetic wounds

Diabetic wounds arise great attention as they are difficult to heal and easily suffer from serious bacterial infection. However, the overuse of antibiotics increases the resistance of bacteria and makes common drugs ineffective. Here, we developed a photothermal hydrogel (TFP/NP) composed of tremella fuciformis polysaccharides (TFPs) and cuttlefish ink-derived melanin nanoparticles (NPs). The NPs can produce reliable photothermal effects under near-infrared laser (NIR) irradiation and help to remove the bacteria in the wounds, while TFPs were able to form hydrogel frameworks which possessed anti-inflammatory effects and could be applied to promote wound healing. The TFP/NP hydrogels produced stable thermal effects under NIR irradiation and could continuously kill bacteria. The experiment on a full-layer skin wound sMRSA activity and could improve the healing efficiency. The wounds of the mice could be repaired within 14 days after reasonable treatment. In addition, the hydrogels play significant roles in promoting collagen deposition, anti-inflammation, angiogenesis, and cell proliferation during the therapeutic process. This research provides a simple and effective method for the therapy of bacterial infection wounds through the synergistic effect of TFPs and NPs.

Cerium dioxide nanozyme doped hybrid hydrogel with antioxidant and antibacterial abilities for promoting diabetic wound healing

Diabetic wounds are among the most severe chronic complications in patients with diabetes. Owing to the detrimental effects of high glucose and high levels of reactive oxygen species (ROS) in the wound microenvironment, diabetic wound healing is significantly challenging. To address the issues of elevated ROS levels and infection susceptibility in diabetic wounds, we designed a composite hydrogel system loaded with cerium dioxide nanoparticles (CeO2 NPs) and vancomycin. This hydrogel aimed to reshape the wound microenvironment by continuously consuming ROS and inhibiting infection. Experimental results demonstrated that the CeO2 NPs-loaded hydrogel demonstrated an 85.40% clearance rate of hydroxyl radicals (·OH) and achieved over 90% inhibition against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and effectively promoted the healing of diabetic mouse wounds. This cerium dioxide nanozyme hybrid hydrogel system can exert antioxidative and antibacterial effects and serve as a wound dressing to promote the healing of infected diabetic wounds.

Carbon dots-supported Zn single atom nanozymes for the catalytic therapy of diabetic wounds

Diabetic wound treatment continues to be a significant clinical issue due to higher levels of oxidative stress, susceptibility to bacterial infections, and chronic inflammatory responses during healing. We rationally developed and synthesized an ultra-small carbon dots (C-dots) loaded with zinc single-atom nanozyme (Zn/C-dots) with the aim of promoting wounds healing by nanocatalytic treatment, especially targeting its complex pathological microenvironment. Zinc single atoms and C-dots form a dual catalytic system with higher enzymatic activity. Furthermore, the Zn/C-dots nanozyme effectively enters cells, accumulates at mitochondria, and removes excess ROS, protecting cells from oxidative stress damage and limiting the release of pro-inflammatory cytokines, hence reducing inflammation. Zinc can synergistically increase the antibacterial action of C-dots (the effective antibacterial rate of 100 µg/mL Zn/C-dots was above 90 %). Unlike traditional C-dots, Zn/C-dots can cause endothelial cell migration and the formation of new blood vessels. In vitro cytotoxicity, blood compatibility, and in vivo toxicity studies of Zn/C-dots show that they are biocompatible. We subsequently utilized the Zn/C-dots nanozymes to treat diabetic rats' chronic wounds for external use, combining them with ROS-responsive hydrogels to create an antioxidative system (H-Zn/C-dots). The hydrogels anchored the Zn/C-dots nanozymes to the wound, allowing for long-term treatment. The results revealed that H-Zn/C-dots can considerably reduce inflammation, accelerate angiogenesis, collagen deposition, and promote tissue remodeling at the diabetic wound site. After 14 days, the wound area had decreased to approximately 9.19 %, making it a potential treatment. Statement of significanceAn ultra-small carbon dot with a zinc single-atom nanozyme was designed and manufactured. Zn/C-dots possess antibacterial, ROS-scavenging, and angiogenesis activities. In vivo, the multifunctional ROS-responsive hydrogel incorporating Zn/C-dots could speed up diabetic wound healing.

Salvianolic acid B improves diabetic skin wound repair through Pink1/Parkin-mediated mitophagy

Diabetic skin wound is a disturbing and rapidly evolving clinical issue. Here, we investigated how salvianolic acid B (Sal B) affected the diabetic wound healing process. Following Sal B administration, histopathological damage was investigated by H&E and Masson staining, and CD34, apoptosis and mitophagy markers were measured by immunofluorescence, immunohistochemistry, and western blotting. Migration, proliferation, and mitochondrial function of high glucose (HG) –induced HMEC-1 cells were measured. The effects of si-Parkin on endothelial cell migration, apoptosis and mitochondrial autophagy were examined. Sal B alleviated inflammatory cell infiltration and promoted angiogenesis in skin wound tissue. Apoptosis and mitophagy were ameliorated by Sal B in diabetic skin wound tissues and HG-induced HMEC-1 cells. Parkin inhibition impaired the migratorypromoted cell apoptosis and inhibited mitophagy of HMEC-1 cells. This finding demonstrated that Sal B promoted diabetic skin wound repair via Pink1/Parkin-mediated mitophagy, improved our understanding of the diabetic wound healing process.

Rhein-chitosan in situ hydrogel promotes wound healing in diabetic mice

Chronic inflammation and infection often lead to delayed healing in skin wounds of patients with diabetes, presenting a significant challenge in clinical wound repair. In an effort to tackle this issue, we explored the utilization of the natural compounds Rhein and chitosan in the creation of a crosslinked in situ gel. Developed as Rhein-chitosan in situ hydrogel (CS-Rh gel), this formulation has the ability to gel at body temperature, making it suitable for irregular wounds of varying shapes. Our experimental investigations have demonstrated its excellent biocompatibility, controlled release of Rhein, biodegradability, anti-inflammatory properties, antibacterial effect, as well as its ability to enhance keratinocyte proliferation and migration. Furthermore, in vivo studies have confirmed that CS-Rh gel can effectively mitigate tissue inflammation, promote collagen deposition, and significantly accelerate wound healing in diabetic mice within a short timeframe of two weeks. Consequently, this innovative approach holds promise as a viable therapeutic strategy for supporting the healing of diabetic wounds in a clinical setting.