Conventional Antibiotic Treatment Research Articles

The Staphylococcus aureus ArlS Kinase Inhibitor Tilmicosin Has Potent Anti-Biofilm Activity in Both Static and Flow Conditions.

Staphylococcus aureus can form biofilms on biotic surfaces or implanted materials, leading to biofilm-associated diseases in humans and animals that are refractory to conventional antibiotic treatment. Recent studies indicate that the unique ArlRS regulatory system in S. aureus is a promising target for screening inhibitors that may eradicate formed biofilms, retard virulence and break antimicrobial resistance. In this study, by screening in the library of FDA-approved drugs, tilmicosin was found to inhibit ArlS histidine kinase activity (IC50 = 1.09 μM). By constructing a promoter-fluorescence reporter system, we found that tilmicosin at a concentration of 0.75 μM or 1.5 μM displayed strong inhibition on the expression of the ArlRS regulon genes spx and mgrA in the S. aureus USA300 strain. Microplate assay and confocal laser scanning microscopy showed that tilmicosin at a sub-minimal inhibitory concentration (MIC) had a potent inhibitory effect on biofilms formed by multiple S. aureus strains and a strong biofilm-forming strain of S. epidermidis. In addition, tilmicosin at three-fold of MIC disrupted USA300 mature biofilms and had a strong bactericidal effect on embedded bacteria. Furthermore, in a BioFlux flow biofilm assay, tilmicosin showed potent anti-biofilm activity and synergized with oxacillin against USA300.

In silico design of an epitope-based vaccine against PspC in Streptococcus pneumoniae using reverse vaccinology

BackgroundStreptococcus pneumoniae is a major pathogen that poses a significant hazard to global health, causing a variety of infections including pneumonia, meningitis, and sepsis. The emergence of antibiotic-resistant strains has increased the difficulty of conventional antibiotic treatment, highlighting the need for alternative therapies such as multi-epitope vaccines. In this study, immunoinformatics algorithms were used to identify potential vaccine candidates based on the extracellular immunogenic protein Pneumococcal surface protein C (PspC). MethodThe protein sequence of PspC was retrieved from NCBI for the development of the multi-epitope vaccine (MEV), and potential B cell and T cell epitopes were identified. Linkers including EAAAK, AAY, and CPGPG were used to connect the epitopes. Through molecular docking, molecular dynamics, and immunological simulation, the affinity between MEV and Toll-like receptors was determined. After cloning the MEV construct into the PET28a (+) vector, SnapGene was used to achieve expression in Escherichia coli. ResultThe constructed MEV was discovered to be stable, non-allergenic, and antigenic. Microscopic interactions between ligand and receptor are confirmed by molecular docking and molecular dynamics simulation. The use of an in-silico cloning approach guarantees the optimal expression and translation efficiency of the vaccine within an expression vector. ConclusionOur study demonstrates the potential of in silico approaches for designing effective multi-epitope vaccines against S. pneumoniae. The designated vaccine exhibits the required physicochemical, structural, and immunological characteristics of a successful vaccine against SPN. However, laboratory validation is required to confirm the safety and immunogenicity of the proposed vaccine design.

Microbial Pathogens in Aquaponics Potentially Hazardous for Human Health.

The union of aquaculture and hydroponics is named aquaponics-a system where microorganisms, fish and plants coexist in a water environment. Bacteria are essential in processes which are fundamental for the functioning and equilibrium of aquaponic systems. Such processes are nitrification, extraction of various macro- and micronutrients from the feed leftovers and feces, etc. However, in aquaponics there are not only beneficial, but also potentially hazardous microorganisms of fish, human, and plant origin. It is important to establish the presence of human pathogens, their way of entering the aforementioned systems, and their control in order to assess the risk to human health when consuming plants and fish grown in aquaponics. Literature analysis shows that aquaponic bacteria and yeasts are mainly pathogenic to fish and humans but rarely to plants, while most of the molds are pathogenic to humans, plants, and fish. Since the various human pathogenic bacteria and fungi found in aquaponics enter the water when proper hygiene practices are not applied and followed, if these requirements are met, aquaponic systems are a good choice for growing healthy fish and plants safe for human consumption. However, many of the aquaponic pathogens are listed in the WHO list of drug-resistant bacteria for which new antibiotics are urgently needed, making disease control by antibiotics a real challenge. Because pathogen control by conventional physical methods, chemical methods, and antibiotic treatment is potentially harmful to humans, fish, plants, and beneficial microorganisms, a biological control with antagonistic microorganisms, phytotherapy, bacteriophage therapy, and nanomedicine are potential alternatives to these methods.

Edge-selective covalent passivation of black phosphorus nanosheets by fullerene C70 toward enhanced antimicrobial performance

In the fight against bacterial infection, conventional antibiotic treatment encounters the formidable challenges of drug resistance and sluggish development. Non-metallic two-dimensional (2D) nanomaterials such as black phosphorus (BP) have emerged as promising non-antibiotic antimicrobial candidates due to its peculiar physiochemical properties, but face hurdles including low ambient stability and limited antibacterial activity, hindering its widespread utilization in disinfection. Herein, few-layer BP nanosheets (BPNSs) were covalently passivated by edge-selectively grafting fullerene C70 via a one-step solid-state mechanochemical route, and for the first time the covalently functionalized BPNSs is employed in disinfection. Fullerene edge-selective covalent passivation not only effectively overcomes the obstacles of poor ambient stability, but also substantially enhances the antibacterial activities of BPNSs. The BPNSs-C70 hybrid (denoted as BPNSs-C70) was applied as a novel non-metallic and non-antibiotic nano-antibacterial agent. Under 660 nm visible light irradiation, BPNSs-C70 demonstrates high generation capacity of reactive oxygen species (ROS), resulting in boosted in vitro and in vivo antibacterial efficacies against methicillin-resistant Staphylococcus aureus (MRSA) relative to the pristine BPNSs with exceptional biocompatibility. The significantly enhanced antibacterial performance of BPNSs-C70 is attributed to the synergistically improved singlet oxygen (1O2) and hydroxyl radicals (•OH) generation originated from the intramolecular electron transfer from BPNSs to C70.

Type-I Photosensitizer-Triggered Controllable Carbon Monoxide Release for Effective Treatment of Staph Skin Infection.

Staphylococcus aureus (S. aureus) infection is a major infectious skin disease that is highly resistant to conventional antibiotic treatment and host immune defense, leading to recurrence and exacerbation of bacterial infection. Herein, we developed a photoresponsive carbon monoxide (CO)-releasing nanocomposite by integrating anion-π+ type-I photosensitizer (OMeTBP) and organometallic complex (FeCO) for the treatment of planktonic S. aureus and biofilm-associated infections. After optimizing the molar ratio of FeCO and OMeTBP, the prepared nanoparticles, OMeTBP@FeCONPs, not only ensured sufficient loading of CO donors and efficient CO generation but also showed negligible free ROS leakage under light irradiation, which helped to avoid tissue damage caused by excessive ROS. Both in vitro and in vivo results demonstrated that OMeTBP@FeCONPs could effectively inhibit S. aureus methicillin-resistant S. aureus (MRSA), and bacterial biofilm. Our design has the potential to overcome the resistance of conventional antibiotic treatment and provide a more effective option for bacterial infections.

The curative effect of ozonated bidistilled water on Escherichia coli-induced endometritis in rats.

Endometritis is a prevalent and challenging condition that affects livestock, and its effective treatment is the use of intrauterine antibiotics. Antibiotic use may lead to negative consequences, including residue in tissues and the emergence of antibiotic resistance. The aim of this study was to assess the therapeutic potential of ozonated bidistilled water in the treatment of Escherichia coli-induced endometritis in rat models, comparing it to conventional antibiotic treatment. A total of 21 female Wistar Albino rats were used for this study. E. coli from the uterus of cows with endometritis at a concentration of 1.0×109 cfu/mL inoculated into rat uteruses. After inoculation, it was confirmed macroscopically that experimental endometritis was induced in all individuals. And, the rats with endometritis were randomly divided into three groups treated with intrauterine bidistilled water enriched with ozone, antibiotics and 0.9% NaCl. The uterine tissues were examined histopathologically. In the semiquantitative analyses, significantly lower histopathological scores were observed for both the bidistilled water enriched with ozone and antibiotic-treated endometritis groups compared to the control group (p < 0.05). Ozone-enriched bidistilled water can be used in the treatment of experimentally induced endometritis in rats, and can provide effective microbiological and histopathological improvement. Further studies involving larger populations of different species are needed to determine the medical suitability of this new treatment.

Immune Targeting of Mycobacteria through Cell Surface Glycan Engineering.

Mycobacteria and other organisms in the order Mycobacteriales cause a range of significant human diseases, including tuberculosis, leprosy, diphtheria, Buruli ulcer, and non-tuberculous mycobacterial (NTM) disease. However, the intrinsic drug tolerance engendered by the mycobacterial cell envelope undermines conventional antibiotic treatment and contributes to acquired drug resistance. Motivated by the need to augment antibiotics with novel therapeutic approaches, we developed a strategy to specifically decorate mycobacterial cell surface glycans with antibody-recruiting molecules (ARMs), which flag bacteria for binding to human-endogenous antibodies that enhance macrophage effector functions. Mycobacterium-specific ARMs consisting of a trehalose targeting moiety and a dinitrophenyl hapten (Tre-DNPs) were synthesized and shown to specifically incorporate into outer-membrane glycolipids of Mycobacterium smegmatis via trehalose metabolism, enabling recruitment of anti-DNP antibodies to the mycobacterial cell surface. Phagocytosis of Tre-DNP-modified M. smegmatis by macrophages was significantly enhanced in the presence of anti-DNP antibodies, demonstrating proof-of-concept that our strategy can augment the host immune response. Because the metabolic pathways responsible for cell surface incorporation of Tre-DNPs are conserved in all Mycobacteriales organisms but absent from other bacteria and humans, the reported tools may be enlisted to interrogate host-pathogen interactions and develop immune-targeting strategies for diverse mycobacterial pathogens.

Mechanically Robust Dissolving Microneedles Made of Supramolecular Photosensitizers for Effective Photodynamic Bacterial Biofilm Elimination

Bacterial biofilms pose severe threats to public health worldwide and are intractable by conventional antibiotic treatment. Antimicrobial photodynamic therapy (PDT) is emerging as a promising strategy for eradicating biofilms by virtue of low invasiveness, broad-spectrum antibacterial activity, and nondrug resistance. However, its practical efficacy is impeded by the low water solubility, severe aggregation, and poor penetration of photosensitizers (PSs) into the dense extracellular polymeric substances (EPS) of biofilms. Herein, we develop a dissolving microneedle (DMN) patch composed of a sulfobutylether-β-cyclodextrin (SCD)/tetra(4-pyridyl)-porphine (TPyP) supramolecular PS for enhanced biofilm penetration and eradication. The inclusion of TPyP into the SCD cavity can drastically inhibit the aggregation of TPyP, thereby allowing for nearly tenfold reactive oxygen species production and high photodynamic antibacterial efficacy. Moreover, the TPyP/SCD-based DMN (TSMN) possesses excellent mechanical performance that can easily pierce the EPS of biofilm with a penetration depth of ∼350 μm, enabling sufficient contact of TPyP with bacteria and optimal photodynamic elimination of bacterial biofilms. Furthermore, TSMN could efficiently eradicate Staphylococcus aureus biofilm infection in vivo with good biosafety. This study offers a promising platform for supramolecular DMN for efficient biofilm elimination and other PDTs.

Effect of in vitro simulated digestion on the anti-Helicobacter Pylori activity of different Propolis extracts

Helicobacter pylori (HP) is among the most common pathogens causing infection in humans worldwide. Oxidative stress and gastric inflammation are involved in the progression of HP-related gastric diseases, and they can be targeted by integrating conventional antibiotic treatment with polyphenol-enriched natural products. In this work, we characterised three different propolis extracts and evaluated their stability under in vitro simulated gastric digestion, compared to their main constituents alone. The extract with the highest stability to digestion (namely, the dark propolis extract, DPE) showed a minimum bactericidal concentration (MBC) lower than 1 mg/mL on HP strains with different virulence factors. Finally, since urease is one of the virulence factors contributing to the establishment of a microenvironment that promotes HP infection, we evaluated the possible inhibition of this enzyme by using molecular docking simulations and in vitro colorimetric assay, showing that galangin and pinocembrin may be involved in this activity.

Pharmacoeconomic Analysis of the Different Therapeutic Approaches in Control of Bovine Mastitis: Phytotherapy and Antimicrobial Treatment.

Mastitis in dairy cows is responsible for major economic losses on dairy farms worldwide as the most expensive and prevalent disease in dairy cattle. In spite of the fact that antibiotic therapy still remains the main treatment strategy for bovine mastitis, concerns about the shortcomings of this treatment approach are continuously raised. Hence, research on alternative treatments with increased effectiveness and reduced costs is needed. Therefore, we conducted a pharmacoeconomic analysis of conventional antibiotic vs. a proposed Phyto-Bomat treatment based on essential oils in bovine mastitis therapy. Treatments were compared from the farmer's perspective in the domain of costs (expressed in total, direct and indirect, cost differences) and effectiveness (expressed in daily milk yield differences). Economic calculations were based on data from a dairy farm in Serbia. The average cost of conventional antibiotic treatment was estimated at EUR 80.32 consisting of therapy costs, veterinary services and milk rejection costs at EUR 16.54, EUR 17.68 and EUR 46.10, respectively. The average cost of Phyto-Bomat treatment was estimated at EUR 76.34 with therapy costs of EUR 34.34, veterinary costs of EUR 32.00 and rejection of milk costs of only EUR 10.00. Therefore, Phyto-Bomat results in cost savings approximating EUR 4 per each mastitis episode with the highest cost reductions obtained in milk rejection costs. This estimation of Phyto-Bomat's economic benefits could be used as a starting point for the inclusion of this formulation as an alternative treatment approach with a focus on subclinical mastitis since it contributes to most of the financial losses.

Osteomyelitis therapy with hyperbaric oxygen

Osteomyelitis is a diffuse inflammation that affects the periosteum, cortical bone, and cancellous bone components. The inside of the bone that has been infected will become soft and experience swelling which causes the tissue to press against the outer wall of the bone and the blood vessels in the marrow whichcauses blood flow and oxygen supply to the bone decrease drastically. Usually surgical therapy is needed to treat osteomyelitis, but if the patient's physical condition does not allow it, hyperbaric oxy-gen therapy can be done to increase the supply of oxygen to the hypoxic bones. Hyperbaric oxygen therapy is an adjunctto conven-tional antibiotic or surgical treatment of resistant osteomyelitis, using large, multiposition or monoposition pressure tubes for one patient. The patients are given 100% oxygen with a pressure dose of 2-2.4 Atm for 90-120 minutes per day; five or six times per week for 8 weeks or more. Overall usage ranges from 80 to over 130 hours.

Directions in the development of modern and promising antimicrobial agents

The use of antibiotics is becoming increasingly limited. This is mainly due to the development of resistance to pathogenic bacteria, and, over time, more and more bacteria will become resistant to antimicrobials. This problem inevitably leads to the conclusion that studies into alternative methods of combating pathogens, which are necessary to develop sufficiently reliable and effective therapies for bacterial infections, are indispensable. This review highlights some recent developments in conventional antibiotic and non-antibiotic treatment strategies. It has been shown that traditional antibacterial targets include derivatives of known antibiotic classes, new chemical classes with new targets, as well as unknown or undefined agents with unclear targets. Promising strategies for combating microbial pathogens have been identified, including new targets, namely, toxin secretion systems, biofilm formation, and adhesion mechanisms that affect quorum sensing of microbial populations. In addition, it is important to use new antimicrobial agents with other, non-antibiotic, mechanisms of action: phage and phage-derived peptides, microbiota-modulating therapies, and enhancing immune response.

Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis.

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft tissue infections, septic arthritis and infection-associated inflammation destroy cartilage that does not regenerate once damaged. Herein, we show that glycolytic pathways are shared by methicillin-resistant Staphylococcus aureus (MRSA) proliferation and host inflammatory machinery in septic arthritis. MRSA readily penetrates host cells and induces proinflammatory cascades that persist after conventional antibiotic treatment. The glycolysis-targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti-inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferation and re-emergence of intracellular MRSA. Combinatorial adjuvant administration of DMF with antibiotics alleviated clinical symptoms of septic arthritis by suppressing bacterial burden and curbing inflammation to protect cartilage and bone. Our results provide mechanistic insight into the regulation of glycolysis in the context of infection and host inflammation toward development of a novel therapeutic paradigm to ameliorate joint bioburden and destruction in septic arthritis.

A RARE CASE OF ENTEROCOCCUS FAECALIS BIOPROSTHETIC AORTIC VALVE ABSCESS

A RARE CASE OF ENTEROCOCCUS FAECALIS BIOPROSTHETIC AORTIC VALVE ABSCESS

에스상 정맥동의 저형성을 동반한 악성 외이도염 1예

Malignant external otitis is an inflammatory disease that can spread to the external ear canal, surrounding tissues, and the base of skull. It is important for diabetes patients to control blood sugar and choose appropriate antibiotics. If unsuccessfully treated by conventional antibiotic treatment, it can cause complications such as facial neuropathy, mastoiditis, sigmoid sinus thrombosis, multiple cranial nerve palsy, and even death in severe cases. In case of patients have bony erosion of external auditory canal or need extensive exposure to the middle ear cavity, surgical treatment such as canal wall up mastoidectomy, or canal wall down mastoidectomy could be considered. In treating patients with malignant external otitis and otitis media, it is very significant to evaluate dura plate and sigmoid sinus through preoperative imaging such as computerized tomography and magnetic resonance imaging. We report our experience of treating the case of malignant external otitis with hypoplasia of sigmoid sinus showing the thickening of the dura membrane by inflammation.

Local treatment of canine chronic ulcerative stomatitis using adipose tissue derived mesenchymal stem cells – a case report

Canine chronic ulcerative stomatitis (CCUS) is a condition characterized by chronic pain, associated with oral ulceration, inflammation and mucosal necrosis. We report the case of a 5-year-old female Akita Inu canine with sialorrhea, halitosis, oral ulcers, submandibular lymphadenopathy and substantial oral discomfort. After a poor response to conventional scaling and antibiotic treatment, the patient improved when prednisolone was administered at a dose of 1mg / kg daily. Aggressive immunosuppressive treatments and teeth extractions were ruled out, so cellular therapy was started. This study evaluates the effect of allogeneic thawed and expanded canine adipose tissue-derived mesenchymal stem cells (AT-MSCs) therapy in a case of CCUS. Four local injections of AT-MSCs (3.5 to 8×106 cells) were administered every 3–4 weeks under general anesthesia and immediately after dental scaling. A higher dose of AT-MSCs (22×106 cells) was injected 5 months later under the same conditions. After the AT-MSCs treatment, the patient showed an improvement in oral lesions and reduction of oral pain for at least 4 weeks. We concluded that a dose of 1×106 AT-MSCs/kg body weight reduced the symptoms of CCUS for at least one month in this case. To our knowledge, this is the first description of allogeneic AT-MSC therapy on canine chronic ulcerative stomatitis.

Value of combined detection of serum amyloid A, C-reactive protein and procalcitonin in differential diagnosis of respiratory tract infection in children of China

Objective To explore the diagnostic value of combined detection of serum amyloid A (SAA), C-reactive protein (CRP) and procalcitonin (PCT) in children with bacteria or non-bacterial respiratory tract infection. Methods 200 children with respiratory tract infections diagnosed in our hospital were included in the study. According to the results of the aetiological examination, they were divided into bacterial infection group and non-bacterial infection group. At the same time, 100 healthy children admitted to the hospital for physical examination during the same period were selected as the healthy subjects control group. Changes in serum SAA, PCT and CRP in three groups were compared. Comparison of a positive rate of the single index and combined detection were performed. Children with bacterial infections were treated with conventional antibiotics. The changes in serum SAA, PCT and CRP in the infection group before and after treatment were compared. The efficacy of SAA, PCT and CRP alone and in combination was compared. Results The serum SAA, PCT and CRP levels in the bacterial infection group were higher than those in the non-bacterial infection group and healthy children, and the differences were statistically significant. The positive detection rates and combined detection rates of serum SAA, PCT and CRP in the bacterial infection group were higher than those in the non-bacterial infection group and the healthy subject's control group. After conventional antibiotic treatment, serum SAA, PCT and CR levels in children with bacterial infection were significantly decreased. Conclusion The combined detection based on SAA, CRP and PCT can effectively identify and diagnose respiratory tract infection in children, providing a certain reference for the promotion of the diagnostic scheme. Key messages Serum SAA, PCT and CRP were highly expressed in children with respiratory tract infection, and the expression level was the highest in children with bacterial pneumonia. The combined detection of serum SAA, CRP and PCT indicators have higher diagnostic efficiency and can effectively make a differential diagnosis of respiratory tract infection in children.

HERBS - THE NATURAL ALTERNATIVE TO TREAT THE PERIODONTAL DISEASES

Herbal extracts are used in dentistry for treatment of various dental disorders. The natural photochemical could offer an effective alternative to antibiotics and represent a promising approach to prevention and therapeutic strategies for various oral infections. The herbal remedies have an edge over conventional antibiotic treatment that suffer the limitation of low benefit to high risk as compared to herbal treatment that possess high benefit to low-risk ratio. The literature shows that several herbal formulations have the capacity to control the production of proinflammatory mediators, thereby managing many inflammatory processes. The use of such herbal anti-inflammatory formulations for a longer period of time was found to be safer than that of chemical anti-inflammatory drugs.Studies for assessment of safety and efficacy of herbal remedies are in its infancy. These herbal remedies are expected to widely use in future.

Effect of (+) usnic Acid on Pigment Production in Bacteria

Antibiotic resistance is a universal problem in bacterial infections. Hence it gives high priority for new therapeutic methods to alternate conventional antibiotic treatment. Pigment production is one of the virulence characteristics of bacteria regulated by a quorum-sensing mechanism. Antiquorum sensing activities will not directly affect the viability of bacteria; however, they will reduce the pathogenicity of bacteria. Thereby it gives an adverse probability of the development of drug resistance. Aim of our study is to evaluate the activity of (+) usnic acid on pigment production in Pseudomonas aeruginosa MTCC 2453, Chromobacterium violaceum MTCC 2656 and Serratia marcescens MTCC 8708. (+) usnic acid eluted by column chromatography. Dimethyl sulphoxide (DMSO) was used as the solvent for (+) usnic acid. Antibacterial activity determined by Agar well diffusion and broth microdilution methods. Effect on pigment production was assessed by spectroscopy. (+) usnic acid showed accumulative inhibition as its concentration increases on pigment production by Pseudomonas aeruginosa MTCC 2453, Chromobacterium violaceum MTCC 2656 and Serratia marcescens MTCC 8708. The lowest concentrations of (+) usnic acid manifested 50% inhibition of pigment production was 122.67, 87.73 and 205.26 µg/ml respectively on above mentioned order in bacteria. The concentration of (+) usnic acid that showed pigment production inhibition did not hinder the growth of the bacteria, but it can reduce the virulence of the bacteria. This property can be used to resolve the drug resistance in bacteria. Further studies are required to check the action of (+) usnic acid on other virulence factors of the bacteria to prove the quorum quenching activity.

Wound microenvironment-responsive glucose consumption and hydrogen peroxide generation synergistic with azithromycin for diabetic wounds healing.

Rationale: Chronic wounds are one of the common complications of diabetes. Due to the physiological conditions of diabetic patients, these wounds are more susceptible to bacterial infections and the formation of bacterial biofilms, leading to the inefficiency of conventional antibiotic treatment.Methods: Here, hollow mesoporous silica nanoparticles (HMSN) were used as the nanocarriers for co-delivery of azithromycin (AZM) and glucose oxidase (GOX), achieving a remarkable synergistic effect in chronic diabetic wounds. GOX possesses the catalytic ability to consume glucose and produce H2O2 in the diabetic wound area. The down-regulation of local glucose could effectively improve the chronic diabetic wound microenvironment. Meanwhile, the generated H2O2 effectively inhibits bacterial growth and eradicates bacterial biofilms with the synergism of antibiotics AZM.Results: In the bacteria-infected diabetic cutaneous wound models, the reduction of glucose, generation of H2O2, and release of AZM could effectively reduce the bacterial infection and promote the wounds healing. Moreover, there is no obvious toxicity behavior after the treatment.Conclusions: Therefore, the designed nanosystem could effectively accelerate the diabetic wound healing process by the amelioration of the hyperglycemia microenvironment and the eradication of bacterial biofilms around the wounds, making them promising candidates for clinical transformation.