Enhanced diabetic foot ulcer treatment with a chitosan-based thermosensitive hydrogel loaded self-assembled multi-functional nanoparticles for antibacterial and angiogenic effects.

Inhibiting bacterial growth and promoting angiogenesis are essential for enhancing wound healing in diabetic patients. Excessive oxidative stress at the wound site can also lead to an accumulation of reactive oxygen species. To address these challenges, a smart thermosensitive hydrogel loaded with therapeutic agents was developed. This formulation features self-assembled nanoparticles named CIZ, consisting of chlorogenic acid (CA), indocyanine green (ICG), and zinc ions (Zn2+). These nanoparticles are loaded into a chitosan-ß-glycerophosphate hydrogel, named CIZ@G, which enables rapid gel formation under photothermal effects. The hydrogel demonstrates good biocompatibility and effectively releases drugs into diabetic foot ulcers (DFU) wound. Benefiting from the dual actions of CA and zinc ions, the hydrogel exhibits potent antioxidative and anti-inflammatory effects, enhances the expression of vascular endothelial growth factor (VEGF) and Platelet endothelial cell adhesion molecule-1 (CD31), and promotes angiogenesis. Both in vitro and in vivo experiments confirm that CIZ@G can effectively inhibit the growth of Staphylococcus aureus post-laser irradiation and accelerate wound remodeling within 14 days. This approach offers a new strategy for the treatment of diabetic foot ulcers (DFU), potentially transforming patient care in this challenging clinical area.

Evaluation of Antibiotic-Loaded Bone Cement in Treatment of Infected Diabetic Foot: Systematic Review and Meta-Analysis.

BACKGROUND: Diabetic foot ulcer (DFU) is a common and complex complication in patients with diabetes mellitus. The study of antibiotic-loaded bone cement for the treatment of infected diabetic foot is limited. We aimed to assess the efficacy of antibiotic-loaded bone cement for the treatment of infected diabetic foot. METHODS: The MEDLINE, Embase, BIOSIS, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Knowledge databases were systematically searched up to May 2023 with no language restrictions. We assessed eligible studies for the efficacy of antibiotic-loaded bone cement for the treatment of infected diabetic foot. The standard mean differences (SMDs) or the risk ratios (RRs) were calculated for continuous or dichotomous data, respectively. Data were analysed using the Cochrane Collaboration's RevMan 5.0 software. RESULTS: Nine articles with 565 patients were analysed in our meta-analysis. The wound healing time in ABC group was significantly shorter than that in the control group (SMD = -1.64, 95% CI -2.27 to -1.02 p < 0.00001, I2 = 88%). The ABC group had a significantly decreased number of debridements (SMD = -2.47, 95% CI -4.24 to -0.70, p < 0.00001, I2 = 95%). The pooled data showed no significant difference (RR = 0.41, 95% CI 0.12 to 1.39, p = 0.84, I2 = 0%). CONCLUSION: This is the first meta-analysis comparing the efficacy of antibiotic-loaded bone cement for the treatment of infected diabetic foot. Antibiotic-loaded bone cement treatment significantly shortened the wound healing time and reduced the number of debridements without increasing the incidence of complications. TRIAL REGISTRATION: PROSPERO CRD42023406017.

Recurrence rates after healing in patients with neuroischemic diabetic foot ulcers healed with and without sucrose octasulfate-impregnated dressings: A 1-year comparative prospective study.

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

COX-2 targeted therapy for diabetic foot ulcers using T7-enhanced CS-PVA membranes.

Diabetic foot ulcers can lead to severe complications, including infection, gangrene, and even amputation, significantly impacting patients' quality of life. The application of anti-inflammatory compounds loaded into chitosan membranes offers targeted therapeutic effects, reducing inflammation and promoting tissue regeneration. This study evaluates the therapeutic efficacy of T7, a selective COX-2 inhibitor, incorporated into chitosan-polyvinylalcohol (CS-PVA) membranes for diabetic wound treatment. Cytotoxicity analysis showed high cell viability across various T7 concentrations, indicating minimal cytotoxicity. In silico pharmacology identified 98 potential inflammation-related targets for T7, further supported by GO and KEGG enrichment analyses. Developmental toxicity tests on zebrafish embryos indicated no significant toxicity up to 100 µM concentration. SEM and FTIR analyses confirmed the successful incorporation of T7 into the CS-PVA membrane, while XRD analysis indicated structural stability. The drug release assay demonstrated a sustained release profile, crucial for prolonged therapeutic efficacy. Antibacterial activity assays revealed significant inhibition of common pathogens. In vivo wound healing assays showed accelerated wound closure and enhanced collagen deposition, with histological and immunohistochemistry analyses supporting improved tissue architecture and reduced inflammation. Gene expression analysis confirmed reduced inflammatory markers. These findings suggest that T7-loaded CS-PVA membranes offer a promising, multifaceted approach to diabetic wound treatment, combining anti-inflammatory, antimicrobial, and collagen-promoting properties for effective wound healing.

Combination therapy of negative pressure wound therapy and antibiotic-loaded bone cement for accelerating diabetic foot ulcer healing: A prospective randomised controlled trial.

Negative pressure wound therapy (NPWT) and antibiotic-loaded bone cement (ALBC) are commonly used treatments for diabetic foot ulcers (DFUs). However, the combined efficacy of these two modalities remains unclear. This clinical study aimed to assess the effectiveness and underlying mechanisms of NPWT&ALBC in the management of DFUs. A total of 28 patients were recruited, 16 of whom served as controls and received only NPWT, whilst 12 received NPWT&ALBC. Both groups underwent wound repair surgery following the treatments. Blood samples were obtained to detect infections and inflammation. Wound tissue samples were also collected before and after the intervention to observe changes in inflammation, vascular structure and collagen through tissue staining. Compared with the NPWT group, the NPWT&ALBC group exhibited a superior wound bed, which was characterised by reduced inflammation infiltration and enhanced collagen expression. Immunostaining revealed a decrease in IL-6 levels and an increase in α-SMA, CD68, CD206 and collagen I expression. Western blot analysis demonstrated that NPWT&ALBC led to a decrease in inflammation levels and an increase in vascularization and collagen content. NPWT&ALBC therapy tends to form a wound bed with increased vascularization and M2 macrophage polarisation, which may contribute to DFUs wound healing.

Granular Porous Nanofibrous Microspheres Enhance Cellular Infiltration for Diabetic Wound Healing.

Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic-co-glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an in vitro cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.

Does complete resection of infected bone improve clinical outcomes in patients with diabetic foot osteomyelitis?

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1.

Accelerating diabetic wound healing with Ramulus Mori (Sangzhi) alkaloids via NRF2/HO-1/eNOS pathway.

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus. Ramulus Mori (Sangzhi) alkaloids (SZ-A), an approved oral medication for type 2 diabetes, have not been explored for their potential to enhance the processes involved in diabetic wound healing. This study aims to investigate SZ-A's role in diabetic wound healing mechanisms. The in vivo experimentation involves dividing the subjects into NC and SZ-A groups, with SZ-A dosed at 200 and 400 mg/kg, to assess the therapeutic efficacy of SZ-A. The results of the animal studies show that SZ-A intervention accelerates the processes of diabetic angiogenesis and wound healing in a manner dependent on its concentration. Additionally, a pathological model using advanced glycation end products (AGEs) in HUVECs demonstrates SZ-A's cytoprotective effect. In vitro, SZ-A intervention significantly increases cell proliferation, migration and tube formation, protecting HUVECs from oxidative stress injury induced by AGEs. Mechanistically, SZ-A exerts a protective effect on HUVECs from oxidative stress damage through the activation of the NRF2/HO-1/eNOS signaling pathway. The findings suggest that SZ-A exhibits considerable potential as a promising candidate for treating DFUs, which will aid in more effectively integrating plant-based therapies into clinical settings.

Microenvironment-responsive, multimodulated herbal polysaccharide hydrogel for diabetic foot ulcer healing.

Diabetic ulcers (DUs) usually suffer from severe infections, persistent inflammation, and excessive oxidative stress during the healing process, which led to the microenvironmental alternation and severely impede DU healing, resulting in a delayed wound healing. Therefore, it is particularly important to develop a medical dressing that can address these problems simultaneously. To this end, self-healing composite hydrogels were prepared in this study utilizing Bletilla striata polysaccharide (BSP) and Berberine (BER) with borax via borate ester bond. The chemical and mechanical properties of the BSP/BER hydrogels were characterized, and their wound healing performance was investigated in vivo and in vitro. The results showed that the BSP/BER hydrogel significantly accelerated wound healing in DU mice with the healing rate of 94.90 ± 1.81% on the 14th day by using BSP/BER5, and this outstanding performance was achieved by the multi-targeted biological functions of antibacterial, anti-inflammatory and antioxidant, which provided favorable microenvironment for orderly recovery of the wound. Aside from exhibiting the antibacterial rate of over 90% against both Escherichia coli and Staphylococcus aureus, the BSP/BER5 hydrogel could significantly reduce NO levels 4.544 ± 0.32 µmol/L to exert its anti-inflammatory effects. Additionally, it demonstrated a hemolysis rate and promotes cell migration capabilities at (34.92 ± 1.66%). With the above features, the developed BSP/BER hydrogel in this study could be the potential dressing for clinical treatment of DU wound.

Photothermal and Antibacterial PDA@Ag/SerMA Microneedles for Promoting Diabetic Wound Repair.

Diabetic foot ulcer (DFU) is a common and severe complication of diabetes characterized by wound neuropathy, ischemia, and susceptibility to infection, making its treatment difficult. Dressings are commonly used in treating diabetic wounds; however, they have disadvantages, including lack of flexibility and mechanical strength, lack of coagulation activity, resistance to biodegradation, and low drug delivery efficiency. Developing more effective strategies for diabetic wound treatment has become a new focus. Microneedles (MN) can be used as a drug delivery platform for DFU wounds, allowing safe, effective, painless and minimally invasive medication administration through the skin. Herein, PDA@Ag/SerMA microneedles were prepared by combining the photothermal properties of polydopamine (PDA), the antimicrobial properties of argentum (Ag), and the ability of sericin methacryloyl (SerMA) to promote cell mitosis to accelerate wound healing and treat diabetic ulcer wounds. The results revealed that PDA@Ag/SerMA microneedles exhibited approximately 100% antimicrobial efficacy against Staphylococcus aureus and Escherichia coli under 808 nm near-infrared (NIR) irradiation. Furthermore, the wound healing rate of mice reached 95% within 12 days, which demonstrated the excellent antibacterial properties and wound healing efficacy of PDA@Ag/SerMA microneedles at cellular and animal levels, providing a potential solution for treating DFU.

MCC950 promotes diabetic wound healing through modulating macrophage polarization in an MDSC-dependent manner.

Diabetic foot ulcers (DFUs) are serious skin injuries whereby the wound healing process is frequently stalled in the inflammatory phase. Currently, there is a lack of effective therapeutic strategies. MCC950, a highly selective nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor, has been reported to show strong anti-inflammation effects in many diseases. In this study, we unveiled the role of MCC950 in DFU mice model and its underlying molecular mechanisms. MCC950 could significantly accelerate diabetic wound healing, as shown by shortened healing time and better healing quality. Moreover, increased M2 phenotype macrophages and decreased pro-inflammatory genes were observed in MCC950-treated DFU mice. Additionally, myeloid-derived suppressor cells (MDSCs) were significantly increased in blood, spleen and wound tissues at different time courses. Specifically, MCC950 could recruit more MDSCs in an early phase in DFU mice, exerting an anti-inflammation effect. We identified the cell crosstalk between macrophages and MDSCs with MCC950 treatment process. Depleting MDSCs in vivo could eliminate the therapeutic effect of MCC950 on diabetic wound healing through inhibiting M2 macrophage polarization. Besides, MDSCs isolated from the wounds of MCC950 or saline treated mice were cocultured with bone marrow derived macrophage (BMDM) in a transwell system. Results confirmed that MDSCs sorted from MCC950 treated mice caused a significant increased percentage of M2 macrophages. Collectively, our findings suggest that the administration of MCC950 has the potential to accelerate diabetic wound healing by promoting M2 macrophage polarization in an MDSC-dependent manner. This study provides valuable insights into the utilization of pharmacological agents for DFU treatment.

Three versus six weeks of post-amputation antibiotic therapy in diabetic forefoot osteomyelitis with positive culture for residual infected bone.

OBJECTIVES: In 2021 in our university hospital, it was decided in a multidisciplinary consultation meeting on osteoarticular infection in patients with diabetic foot to reduce the duration of post-amputation antibiotic therapy from six to three weeks in patients with diabetic forefoot osteomyelitis and residual bone infection. This study aimed to compare clinical outcomes in this group of patients, before vs after the change in practice introduced in 2021. METHODS: In this before-after study, we included all cases reported between January 2016 and August 2023 in the University Hospital of Reims. RESULTS: We included 113 patients; between 2016 and 2020, 56 (49.5 %) received six weeks of post-amputation antibiotic therapy, and between 2021 and 2023, 57 (50.5 %) received three weeks of therapy. Over six months of follow-up, overall cure rate was 95 %. Treatment failure did not differ between groups. CONCLUSION: Three weeks of post-amputation antibiotic therapy in diabetic patients with forefoot osteomyelitis and residual bone infection is effective.

Computer-aided drug design to generate a unique antibiotic family.

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 µg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs.

Microbiological characterization of neuropathic diabetic foot infection: a retrospective study at a Portuguese tertiary hospital.

Diabetic foot infection imposes a significant burden and is the major cause of nontraumatic limb amputation. Adequate patient management with effective antibiotic therapy is crucial.This retrospective cohort study aimed to characterize the microbiology and resistance patterns of moderate to severe neuropathic diabetic foot infection in patients hospitalized at a tertiary referral hospital between January 2020 and June 2023. Deep tissue specimens from ulcers were collected for culture.Sixty inpatients were included (62% male, mean age 59.1 ± 11.5 years). Osteomyelitis was present in 90% of the patients. Among 102 microorganisms (average of 1.91 ± 1.25 pathogens per patient), 60.8% were gram-positive bacteria, 31.4% were gram-negative, 3.92% were anaerobic bacteria, and 3.92% were fungi. Staphylococcus aureus (19%) and Enterococcus faecium (17%) were the most common. Pseudomonas aeruginosa (8%) and bacteria of the Enterobacterales family (24%) accounted for all the isolated gram-negative bacteria. Sixteen percent of Staphylococcus aureus and 67% of coagulase-negative Staphylococci were resistant to methicillin. Resistance to ampicillin was found in 11% of Enterococci. All Pseudomonas aeruginosa isolates were sensitive to piperacillin-tazobactam, ceftazidime, or cefepime. Among the Enterobacterales, resistance rates were 35% for piperacillin-tazobactam, 38% for ceftazidime, 21% for cefepime, and 13% for carbapenems.Although the prevalence of methicillin-resistant staphylococci was lower than that in other studies, carbapenem resistance among gram-negative bacteria warrants attention. This study highlights the importance of understanding local epidemiology for effective diabetic foot infection management and resistance mitigation.

Biologically Active Sheep Colostrum for Topical Treatment and Skin Care.

Colostrum is gaining popularity in cosmetic products. The present study compared the composition and selected biological properties of colostrum from Polish sheep (colostrum 1) and Swiss sheep (colostrum 2), particularly those that can affect healthy or diseased skin. The antioxidant activity of the colostrums was measured using ABTS and DPPH assays. The effect on the proliferation of human skin fibroblasts, neonatal epidermal keratinocytes, and human diabetic fibroblast (dHF) cells isolated from diabetic foot ulcers was also assayed in vitro by MTT and Presto Blue tests, respectively. The colostrum simulated dHF cell proliferation by up to 115.4%. The highest used concentration of colostrum 1 stimulated normal fibroblast proliferation by 191.2% (24 h) and 222.2% (48 h). Both colostrums inhibited epidermal keratinocyte viability. The influence of the colostrums on the expression of genes related to proliferation (Ki67) and immune response (IL-6, PTGS-2, TSG-6) in dHF cells were compared. Colostrum 1 increased the rate of wound closure (scar test). Analysis of total fat, protein and fatty acid content found the Polish colostrum to be a richer source of fat than the Swiss colostrum, which contained a larger amount of protein. Both colostrums exhibit properties that suggest they could be effective components in cosmetic or medicinal formulations for skin care, especially supporting its regeneration, rejuvenation, and wound healing.

Hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway-based ulcer-healing mechanism of Astragalus Aqueous extract in diabetic foot rats.

The main objective of this work was to investigate the mechanism of Astragalus aqueous extract ulcer healing in diabetic foot model rats through the hypoxia-inducible factor 1-alpha (HIF-1ɑ)/vascular endothelial growth factor (VEGF) signalling pathway. Fifty specific-pathogen-free male Sprague Dawley rats were divided into blank (A), model control (B), Astragalus extract (C) and mupirocin (D) treatment groups. Group A received a regular diet, whereas the other groups received a high-fat/high-sugar diet and intraperitoneal streptozotocin injections to induce diabetes. Diabetic foot ulcers were created via skin excision. Subsequently, ulcers were debrided daily. Groups B, C and D received wet saline gauze, wet gauze with Astragalus extract and gauze with mupirocin, respectively, on the affected area. Group A received no treatment. After 14 days, the rats were assessed for ulcer healing and general condition. Immunohistochemistry was used to detect HIF-1ɑ and VEGF levels in the dorsalis pedis artery, and ELISA was used to determine serum IL-6 and CRP levels. The results revealed that Groups C and D had significantly faster ulcer healing compared with Group B (p < 0.01), and ulcer healing was faster in Group C than in Group D (p < 0.01). Group C exhibited notably higher HIF-1ɑ and VEGF protein expression levels compared with Groups B and D (p < 0.01). IL-6 and CRP expression levels in Groups C and D were significantly lower than those in Group B (p < 0.01). In summary, Astragalus aqueous extract effectively treats diabetic foot ulcers by up-regulating HIF-1ɑ and VEGF expression, activating the HIF-1ɑ/VEGF pathway, improving local tissue ischaemia and hypoxia, promoting collateral circulation and enhancing dorsalis pedis artery formation, thereby accelerating ulcer repair in diabetic rats.

Multifunctional Janus Membrane for Diabetic Wound Healing and Intelligent Monitoring.

The complex microenvironment of diabetic wounds often hinders the healing process, ultimately leading to the formation of diabetic foot ulcers and even death. Dual monitoring and treatment of wounds can significantly reduce the incidence of such cases. Herein, a multifunctional Janus membrane (3D chitosan sponge-ZE/polycaprolactone nanofibers-ZP) was developed by incorporating the zinc metal-organic framework, europium metal-organic framework, and phenol red into nanofibers for diabetic wound monitoring and treatment. The directional water transport capacity of the resulting Janus membrane allows for unidirectional and irreversible drainage of wound exudate, and the multifunctional Janus membrane creates up to a 99% antibacterial environment, both of which can treat wounds. Moreover, the pH (5-8) and H2O2 (0.00-0.80 µM) levels of the wound can be monitored using the color-changing property of phenol red and the fluorescence characteristic of Eu-MOF on the obtained membrane, respectively. The healing stages of the wound can also be monitored by analyzing the RGB values of the targeted membrane images. This design can more accurately reflect the wound state and treat the wound to reduce bacterial infection and accelerate wound healing, which has been demonstrated in in vivo experiments. The results provide an important basis for early intervention in diabetic patients.

Bilayer hydrogel with a protective film and a regenerative hydrogel for effective diabetic wound treatment.

Diabetic foot ulcers (DFUs) are one of the most serious complications of diabetes, often leading to necrosis and amputation. DFU is caused by the intricate diabetic microenvironment, including ischemia, hypoxia, hyperinflammation, reduced angiogenesis, and persistent infection. Traditional wound dressings made of single or mixed materials often struggle to meet all the requirements for effective diabetic wound healing. In contrast, multilayer dressings comprising more than single layers have the potential to address these challenges by combining their diverse chemical and physical properties. In this study, we developed a bilayer hydrogel comprising a GelMA-ALG-nano-ZnO protective film and a COL1-PRP regenerative hydrogel for facilitating diabetic wound healing. We demonstrated the protective properties against bacterial infection of the protective film, while highlighting the regenerative potential of the COL1-PRP hydrogel in promoting fibroblast and MUVEC migration, extracellular matrix secretion and deposition, and angiogenesis. Importantly, the bilayer hydrogel exhibited superior efficacy in promoting full-thickness wound healing in a diabetic rat model compared to its single-layer hydrogel counterparts. This multi-layer approach offers a promising strategy for addressing the complexities of diabetic foot treatment and improving clinical outcomes.

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

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