Wound Healing Therapy Research Articles

Single-, Dual-, and Multi-Stimuli-Responsive Nanogels for Biomedical Applications.

In recent years, stimuli-responsive nanogels that can undergo suitable transitions under endogenous (e.g., pH, enzymes and reduction) or exogenous stimuli (e.g., temperature, light, and magnetic fields) for on-demand drug delivery, have received significant interest in biomedical fields, including drug delivery, tissue engineering, wound healing, and gene therapy due to their unique environment-sensitive properties. Furthermore, these nanogels have become very popular due to some of their special properties such as good hydrophilicity, high drug loading efficiency, flexibility, and excellent biocompatibility and biodegradability. In this article, the authors discuss current developments in the synthesis, properties, and biomedical applications of stimulus-responsive nanogels. In addition, the opportunities and challenges of nanogels for biomedical applications are also briefly predicted.

Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair.

Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

Macrofungal Mediated Biosynthesis of Silver Nanoparticles and Evaluation of Its Antibacterial and Wound-Healing Efficacy.

Recently, the utilization of biological agents in the green synthesis of nanoparticles has been given interest. In this study, silver nanoparticles were synthesized from an aqueous extract of macrofungus (mushroom), namely Phellinus adamantinus, in a dark room using 20 µL of silver nitrate. Biosynthesized silver nanoparticles were confirmed by analyzing them using a UV-Vis (ultraviolet-visible) spectrophotometer. The synthesized silver nanoparticles were optimized at different pH and temperatures with various dosages of AgNO3 (silver nitrate) and fungal extracts. The synthesized AgNPs (silver nanoparticles) were characterized using TEM (transmission electron microscopy) and EDX (energy-dispersive X-ray) analyses, which confirmed the presence of silver nanoparticles. The size of the nanosilver particles was found to be 50 nm with higher stability. The mycosynthesized AgNPs showed effective antibacterial activity against strains of Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (E. coli and Pseudomonas aeruginosa) bacteria. The minimum inhibitory concentration (MIC) was found to be 3.125 μg/mL by MIC assay. The MTT assay (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl-2H-tetrazolium bromide) was performed to study cytotoxicity, and reduced cell viability was recorded at 100 μg/mL. Silver-Polygalacturonic acid-Polyvinyl alcohol ((Ag-PGA)-PVA) nanofiber was prepared using the electrospinning method. The in vitro wound scratch assay was demonstrated to study the wound-healing efficacy of the prepared nanofiber. The wound-healing efficacy of the AgNP-incorporated nanofiber was found to be 20% after 24 h. This study will lay a platform to establish a unique route to the development of a novel nanobiomaterial and its application in antibacterial and wound-healing therapy.

A comprehensive review of biosurfactant production and its uses in the pharmaceutical industry.

Biosurfactants are naturally occurring, surface-active chemicals generated by microorganisms and have attracted interest recently because of their numerous industrial uses. Compared to their chemical equivalents, they exhibit qualities that include lower toxic levels, increased biodegradable properties, and unique physiochemical properties. Due to these traits, biosurfactants have become attractive substitutes for synthetic surfactants in the pharmaceutical industry. In-depth research has been done in the last few decades, demonstrating their vast use in various industries. This review article includes a thorough description of the various types of biosurfactants and their production processes. The production process discussed here is from oil-contaminated waste, agro-industrial waste, dairy, and sugar industry waste, and also how biosurfactants can be produced from animal fat. Various purification methods such as ultrafiltration, liquid-liquid extraction, acid precipitation, foam fraction, and adsorption are required to acquire a purified product, which is necessary in the pharmaceutical industry, are also discussed here. Alternative ways for large-scale production of biosurfactants using different statistical experimental designs such as CCD, ANN, and RSM are described here. Several uses of biosurfactants, including drug delivery systems, antibacterial and antifungal agents, wound healing, and cancer therapy, are discussed. Additionally, in this review, the future challenges and aspects of biosurfactant utilization in the pharmaceutical industry and how to overcome them are also discussed.

Significant Enhancement of Fibroblast Migration, Invasion, and Proliferation by Exosomes Loaded with Human Fibroblast Growth Factor 1.

Exosomes possess several inherent properties that make them ideal for biomedical applications, including robust stability, biocompatibility, minimal immunogenicity, and the ability to cross biological barriers. These natural nanoparticles have recently been developed as drug delivery vesicles. To do so, therapeutic molecules must be efficiently loaded into exosomes first. Very recently, we developed a cell-penetrating peptide (CPP)-based platform for loading of nucleic acids and small molecules into exosomes by taking advantage of the membrane-penetration power of CPPs. Here, we extended this simple but effective platform by loading a protein cargo into exosomes isolated from either mesenchymal stem cells from three different sources or two different cancer cell lines. The protein cargo is a fusion protein YARA-FGF1-GFP through the covalent conjugation of a model CPP called YARA to human fibroblast growth factor 1 (FGF1) and green fluorescence protein (GFP). Loading of YARA-FGF1-GFP into exosomes was time-dependent and reached a maximum of about 1600 YARA-FGF1-GFP molecules in each exosome after 16 h. The ladened exosomes were effectively internalized by mammalian cells, and subsequently, the loaded protein cargo YARA-FGF1-GFP was delivered intracellularly. In comparison to YARA, YARA-FGF1-GFP, the unloaded exosomes, and the exosomes loaded with YARA, the exosomes loaded with YARA-FGF1-GFP substantially promoted the migration, proliferation, and invasion capabilities of mouse and human fibroblasts, which are important factors for wound repair. The work extended our CPP-based exosomal cargo loading platform and established a foundation for developing novel wound-healing therapies using exosomes loaded with FGF1 and other growth factors.

An Article on Curcumin Loaded Transferosomes as A Novel Drug Delivery System

Curcumin is a natural compound found in turmeric and has shown potential in treating a variety of diseases due to its anti-inflammatory and antioxidant properties. However, curcumin has low bioavailability and poor solubility in water, which limits its therapeutic efficacy. Transferosomes are specialized lipid vesicles that can encapsulate drugs and other bioactive molecules, allowing them to be delivered to specific target tissues. Curcumin, a natural compound found in turmeric, has been the subject of intense study due to its potential health benefits, including anti-inflammatory and antioxidant properties. Transferosomes are lipid-based nanoparticles that can encapsulate hydrophobic compounds like curcumin and improve their delivery to target tissues. They can also enhance the absorption of drugs through the skin or mucous membranes. Several studies have investigated the potential of curcumin loaded transferosomes in various applications, such as wound healing, cancer treatment, and anti-inflammatory therapy. These studies have shown promising results, indicating that transferosomes could be an effective drug delivery system for curcumin. However, more research is needed to optimize the formulation and improve the stability and shelf-life curcumin-loaded transferosomes. Additionally, the safety and toxicity of these nanoparticles need to be thoroughly evaluated before they can be used in clinical application. In our study we have observed drug content 4.47mg/ml and EE% was found to be 94.8%, the percentage of drug release of curcumin transferosomes was observed as 30.8%at time period of 4hr.

Investigating temperature variability on antioxidative behavior of synthesized cerium oxide nanoparticle for potential biomedical application.

Cerium oxide nanoparticles (CNP) have garnered significant attention due to their versatile redox properties and wound-healing applications. The antioxidative nature of CNP is due to its ability to be oxidized and reduced, followed by the capture or release of oxygen which is used for scavenging reactive oxygen species (ROS). Herein, CNP is produced through a wet chemistry approach and its tunable redox property is tested across a range of temperatures. The synthesized CNP was observed to reveal the signature peak at 245nm indicating a high Ce+3/Ce+4 ratio. Towards evaluating the redox antioxidative behavior, CNPs were subjected to a comprehensive analysis for superoxide dismutase mimetic analysis with riboflavin-mediated nitroblue tetrazolium scavenging assay. The results demonstrated that the redox activity of cerium oxide nanoparticles was strongly influenced by the different temperature ranges. Superoxide dismutase mimetic activity was observed to be reduced with a decrease in temperature as we moved from 4°C (80% activity) to -80°C (47% activity) at 1mM conc of CNP. Similarly, the SOD mimetic activity increased with an increase in temperature from 40°C (72% activity) to 70°C (94% activity). Further, CNP was found to inhibit E. coli (gram+ve) and Enterobacter (gram-ve) beyond 70% simultaneously at 1mM conc, indicating its potential application as a remarkable antimicrobial agent. CNP also inhibited the alpha-amylase activity up to the 60% at 1mM conc suggesting its potential application in antidiabetic wound healing therapy. Overall, the CNP finds its application in mitigating the oxidative stress-related disorder exhibited by its high antioxidative, antimicrobial, and antidiabetic behavior.

Chitosan-based films filled with nanoencapsulated essential oil: Physical-chemical characterization and enhanced wound healing activity

The economic burden of chronic wounds, the complexity of the process of tissue repair and the possibility of resistant bacterial infections, have triggered a significant research interest in the application of natural alternative therapies for wound healing. Biomolecules are intrinsically multi-active, as they affect multiple mechanisms involved in tissue repair phenomenon, including immunomodulatory, anti-inflammatory, cell proliferation, extra cellular matrix remodeling and angiogenesis. Chitosan features a unique combination of attributes, including intrinsic hemostatic, antimicrobial, and immunomodulatory properties, that make it an exceptional candidate for wound management, in the development of wound dressings and scaffolds. In this study, we produced nanoemulsions (NE) loaded with SFO, characterized them, and evaluated their tissue repairing properties. Dynamic light scattering (DLS) analysis confirmed the formation of a nanoemulsion with a droplet size of 21.12 ± 2.31 nm and a polydispersity index (PdI) of 0.159, indicating good stability for up to 90 days. To investigate the potential wound healing effects, SFO-loaded NE were applied on male C57BL/6 mice for seven consecutive days, producing a significantly higher wound closure efficiency (p < 0.05) for the group treated with SFO-loaded NE compared to the control group treated with the saline solution. This finding indicates that the SFO-loaded NE exhibits therapeutic properties that effectively promote wound healing in this experimental model. Then, SFO-loaded NE were incorporated into chitosan:polyvinyl alcohol (PVA)-based films. The inclusion of NE into the polymer matrix resulted in increased lipophilicity reflected by the contact angle results, while decreasing moisture absorption, water solubility, and crystallinity. Moreover, FTIR analysis confirmed the formation of new bonds between SFO-NE and the film matrix, which also impacted on porosity properties. Thermal analysis indicated a decrease in the glass transition temperature of the films due to the presence of SFO-NE, suggesting a plasticizing role of NE, confirmed by XRD results, that showed a decrease in the crystallinity of the blend films upon the addition of SFO-NE. AFM images showed no evidence of NE droplet aggregation in the Chitosan:PVA film matrix. Moisture absorption and water content decreased upon incorporation of SFO-loaded NE. Although the inclusion of NE increased hydrophobicity and water contact angle, the values remained within an acceptable range for wound healing applications. Overall, our results emphasize the significant tissue repairing properties of SFO-loaded NE and the potential of Chitosan:PVA films containing nanoencapsulated SFO as effective formulations for wound healing with notable tissue repairing properties.

Efficacy of one-hour negative pressure wound therapy and magnetic field energy in wound healing.

Wound healing is an important aspect of health but needs further research to identify the effects and interactions of different treatment approaches on healing. The aims of this study were to investigate the effectiveness of one-hour negative pressure wound therapy (NPWT) and compare histological differences between one-hour NPWT and magnetic field energy (MFE) in rats on early-stage wound healing, wound size and angiogenesis. Standardised wounds were created on Wistar rats that were allocated and divided into NPWT, MFE and control groups. Both treatments were applied for 1 hour/day for 10 days. Wound size, histological changes and wound area blood flow were assessed. The wound size of all groups was similar on days 0, 2 and 10. The MFE group's wound size was smaller than the NPWT group on days 4, 6 and 8 (p<0.05). Development of the granulation tissue in both the one-hour NPWT and MFE groups was greater than in the control group. Additionally, the inflammatory phase was shorter, and wounds entered the proliferative stage faster in the MFE group than both of the other groups. Treatment with MFE may be more effective in terms of early stage wound closure and angiogenesis. On the other hand, the NPWT group's wound area blood flow was significantly greater than the other two groups. MFE is superior to one-hour NPWT in terms of wound area and angiogenesis. Furthermore, it is worthwhile to note that one-hour NPWT increases bloodflow in the wound area, which stimulates healing.

Natural Flavonoid-Derived Enzyme Mimics DHKNase Balance the Two-Edged Reactive Oxygen Species Function for Wound Healing and Inflammatory Bowel Disease Therapy.

Rational regulation of reactive oxygen species (ROS) plays a vital importance in maintaining homeostasis of living biological systems. For ROS-related pathologies, chemotherapy technology derived from metal nanomaterials currently occupies a pivotal position. However, they suffer from inherent issues such as complicated synthesis, batch-to-batch variability, high cost, and potential biological toxicity caused by metal elements. Here, we reported for the first time that dual-action 3,5-dihydroxy-1-ketonaphthalene-structured small-molecule enzyme imitator (DHKNase) exhibited 2-edged ROS regulation, catering to the execution of physiology-beneficial ROS destiny among diverse pathologies in living systems. Based on this, DHKNase is validated to enable remarkable therapeutic effects in 2 classic disease models, including the pathogen-infected wound-healing model and the dextran sulfate sodium (DSS)-caused inflammatory bowel disease (IBD). This work provides a guiding landmark for developing novel natural small-molecule enzyme imitator and significantly expands their application potential in the biomedical field.

Evaluation of Gelatin Loaded PRP for Full-thickness Wound Healing in Rabbit Model

In this study, gelatin (GE) will be used as a carrier to enhance platelet-rich plasma's (PRP) effects on the wound-healing process. PRP/GE was created by conjugating 20% GE with freshly prepared autologous PRP. Following rabbits with experimentally generated full-thickness skin wounds, the ability of the skin to regenerate was evaluated. Evaluation considered the macroscopic features of wounds, wound healing rate % and histologic findings for specimens collected after 3, 10 and 21 days. The PRP/GE treated wounds revealed noticeably improved and better closure. This improvement may be attributable to the advantages of combining PRP with GE as a bioactive substance that may regulate the release of growth factors and support angiogenesis. It might be concluded that PRP/GE has the ability to quicken the healing process. The therapeutic impact of PRP was boosted by the GE carrier. According to these data, PRP/GE may be suggested as a viable therapy for wound healing.

Innovative approaches to wound healing: insights into interactive dressings and future directions.

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.

Nano-emodin mediated photodynamic therapy for wound healing of donor site after free gingival graft: A parallel clinical trial

AimThis study aimed to evaluate the effectiveness of nano-emodin (n-Emo) mediated photodynamic therapy (PDT) as an adjunctive therapy to conventional wound care in patients undergoing free gingival graft (FGG) treatment. The study employed a single-center, parallel, two-blind, randomized, controlled trial design. Method and materialA total of 53 patients requiring FGG treatment were randomly assigned to one of three groups: the n-Emo mediated PDT group, the n-Emo gel group, and the control group. The n-Emo mediated PDT group received n-Emo gel on donor site followed by LED (450 nm, 1000 ± 1400 mW/cm2, 60–80 J/cm2, 60 s), the n-Emo gel group received only n-Emo gel on donor site, and the control group received a placebo gel on donor site. All groups received treatment immediately and 48 h after FGG surgery. Wound healing was assessed based on wound area, bleeding, color match, and epithelialization. Postoperative pain perception was evaluated using a Visual Analogue Scale (VAS), and the number of non-steroidal anti-inflammatory drug (NSAID) intakes was recorded. ResultsThe results showed that all groups demonstrated significant improvement in wound healing by day 28, with the n-Emo mediated PDT exhibiting significantly better healing on the 14th, 21st, and 28th day compared to the control group. Additionally, on the 28th day, the n-Emo mediated PDT showed significantly better healing than the n-Emo gel group. The n-Emo mediated PDT also had significantly lower pain scores than the control group. There were no significant differences in the number of NSAID intakes, bleeding, or color match among the groups, but all groups showed improved color match during follow-up. By the third week, all groups had fully epithelialized without significant differences, and no secondary bleeding incidents were reported. ConclusionThe study concludes that n-Emo mediated PDT is an effective adjunctive therapy to conventional wound care for managing complication after surgery at donor site after FGG surgery.

Enhanced drug delivery and wound healing potential of berberine-loaded chitosan-alginate nanocomposite gel: characterization and in vivo assessment.

Berberine-encapsulated polyelectrolyte nanocomposite (BR-PolyET-NC) gel was developed as a long-acting improved wound healing therapy. BR-PolyET-NC was developed using an ionic gelation/complexation method and thereafter loaded into Carbopol gel. Formulation was optimized using Design-Expert® software implementing a three-level, three-factor Box Behnken design (BBD). The concentrations of polymers, namely, chitosan and alginate, and calcium chloride were investigated based on particle size and %EE. Moreover, formulation characterized in vitro for biopharmaceutical performances and their wound healing potency was evaluated in vivo in adult BALB/c mice. The particle distribution analysis showed a nanocomposite size of 71 ± 3.5 nm, polydispersity index (PDI) of 0.45, ζ-potential of +22 mV, BR entrapment of 91 ± 1.6%, and loading efficiency of 12.5 ± 0.91%. Percentage drug release was recorded as 89.50 ± 6.9% with pH 6.8, thereby simulating the wound microenvironment. The in vitro investigation of the nanocomposite gel revealed uniform consistency, well spreadability, and extrudability, which are ideal for topical wound use. The analytical estimation executed using FT-IR, DSC, and X-ray diffraction (XRD) indicated successful formulation with no drug excipients and without the amorphous state. The colony count of microbes was greatly reduced in the BR-PolyET-NC treated group on the 15th day from up to 6 CFU compared to 20 CFU observed in the BR gel treated group. The numbers of monocytes and lymphocytes counts were significantly reduced following healing progression, which reached to a peak level and vanished on the 15th day. The observed experimental characterization and in vivo study indicated the effectiveness of the developed BR-PolyET-NC gel toward wound closure and healing process, and it was found that >99% of the wound closed by 15th day, stimulated via various anti-inflammatory and angiogenic factors.

Hesperidin-loaded cubogel as a novel therapeutic armamentarium for full-thickness wound healing

Wounds are a physical manifestation of injury to the skin causing it to rupture or tear. The process of wound healing naturally restores skin integrity while minimizing the extent of the damage. Hesperidin (HPN) is a natural polyphenolic flavonoid and is effective in treating wounds due to its ability to reduce inflammation and stimulate angiogenesis. However, its use is limited by its poor physicochemical attributes such as poor solubility in water. Recently, nanoparticles, particularly Cubosomes, are found to be promising candidates for advancing wound-healing therapies, owing to their unique properties. The present study was conducted to develop a hydrogel system based on Cubosomes encapsulating HPN (HPN-Cubogel), with the potential to mitigate full-thickness wounds. The therapeutic efficacy of the formulation assessed in the animal model showed that the HPN-Cubogel formulation group exhibited a wound closure rate of 98.96 ± 1.50% after 14 days post-wounding compared to 89.12 ± 2.6% in the control group suggesting superior wound contraction activity. Collagen synthesis was superior in the formulation compared to the control group, as determined through MT staining. In summary, the HPN-Cubogel formulation was found to be the most effective in enhancing full-thickness wound healing.

Molecular docking and molecular dynamics simulations discover curcumin analogs as potential wound healing agents

Chronic non-healing wounds impose a significant economic burden on the healthcare system. Among the existing strategies in wound healing therapy, targeting specific enzymes, namely tyrosyl-tRNA synthetase, TGFBR1, IL-1β, and Pseudomonas aeruginosa MvfR, represents an important aspect of the strategy of wound healing. Our research focuses on creating new curcumin hybrids (SV01-SV20) for harnessing wound healing activities and possesses considerable therapeutic implications. The compounds were designed and evaluated through in-silico screening using Molinspiration Cheminformatics, Osiris Property Explorer, AdmetSAR, and SwissADME. The initial filtering process identified the top 19 hybrids, which were then subjected to docking using the AutoDock tool. The results of the molecular docking analysis indicate that the curcumin hybrids, specifically tyrosyl-tRNA synthetase (SV09, SV15), TGFBR1 (SV01, and SV11), IL-1β (SV07, SV08), and Pseudomonas aeruginosa MvfR (SV09, SV13), showed the most significant binding energies (-8.69, -9.01, -8.49, -8.13, -8.48, -6.14, -9.7, and -9.2 kcal/mol, respectively) among the designed compounds. The binding energies were higher than the standard curcumin, indicating a potentially more substantial interaction with the target. Extensive molecular dynamics simulations confirmed the stability of these derivatives throughout the 100 ns simulation; the ligand-protein complexes maintained structural stability. The designed compounds demonstrated favorable pharmacokinetic properties, drug-likeness scores, bioactivity assessments, adherence to Lipinski's rule of five, and low toxicity risks. Overall, results consistently demonstrated that SV01, SV07, SV08, SV09, SV11, SV13, and SV15 compounds hold significant potential as effective agents in treating chronic wounds.

Adipose Derived Stem Cell‐Conditioned Media As Alternative of Stem Cell Therapy for Diabetic Wound Healing

Diabetes mellitus (DM) is a set of metabolic disorder primarily characterized by chronic hyperglycaemia state, which is linked with several complications including retinopathy, neuropathy, and delayed wound healing. Adipose derived stem cells conditioned media (ADSCs-CM) contains several cytokines, and growth factors that can be used for treatment of diabetes-associated wounds. This study was conducted to explore the therapeutic potential of ADSCs- CM in excisional wound model in diabetic mice. Diabetes was induced in mice through Streptozotocin (STZ). Then, excisional wound splinting model in diabetic mice was developed. Subcutaneous injections of ADSC-CM (pure) and ADSC-CM conjugated with zinc sulphate were applied on the mice wound bed. Wound diameter, weight, and blood glucose levels of all the mice groups were measured at the start and end of the experiment. Additionally, qPCR was performed to analyse the expression level of some crucial genes (MMP-2, NANOG and OCT4) associated with wound healing. Overall, the results showed reduced wound size, blood glucose level, and weight restoration in ADSCs-CM treated mice as compared with control groups. Furthermore, ADSCs-CM also modulated the gene expression of MMP-2, NANOG, and OCT4, contributing to the enhanced wound healing observed in diabetic mice. This suggests ADSC-CM’s potential as an alternative therapeutic option for achieving improved wound healing outcomes in diabetic patients.

Photothermally Enhanced Cascaded Nanozyme‐Functionalized Black Phosphorus Nanosheets for Targeted Treatment of Infected Diabetic Wounds

AbstractDue to the limitations of H2O2 under physiological conditions and defective activity, nanozyme‐catalyzed therapy for infected diabetic wound healing is still a huge challenge. Here, this work designs a novel multifunctional hybrid glucose oxidase (GOx)–CeO2@black phosphorus (BP)/Apt nanosheet that features GOx and CeO2 dual enzyme loading with photothermal enhancement effect and targeting ability for the treatment of infected wounds in type II diabetic mice. Combined with the photothermal properties of the BP nanosheets, the cascade nanozyme effect of GOx and CeO2 is extremely enhanced. The synergistic effect of peroxidase activity and photothermal therapy with targeting aptamer allows for overcoming the catalytic defects of nanozyme and significantly improving in vitro bacterial inhibition rate with 99.9% and 97.8% for Staphylococcus aureus and Escherichia coli, respectively, as well as enhancing in vivo antibacterial performance with the lowest wound remained (0.05%), reduction of infiltration inflammatory cells, and excellent biocompatibility. Overall, this work builds a nanodelivery system with a powerful therapeutic approach, incorporating self‐supplying H2O2 synergistic photothermal and real‐time wound monitoring effect, which holds profound potential as a clinical treatment for infected diabetic wounds.

Advances of Microneedle Patch in Diabetic Wound Healing

Wound healing is an intricate and orderly process of events that occur in response to external trauma, resulting in tissue repair and reconstruction. This process typically involves three phases, including inflammation, angiogenesis, and extracellular matrix remodeling, and any disruption to this process may delay the healing of the wound. Chronic wounds associated with diabetes, in particular, are notorious because they are difficult to handle in a timely and orderly manner. During the treatment of the disease, drugs usually accumulate in the stratum corneum due to the skin barrier, leading to a reduction of the drug's bioavailability. Encouragingly, among the treatment strategies, microneedles (MNs) represent a novel and painless drug delivery method that promotes wound healing in diabetic patients by enabling the drug to reach the dermal layer efficiently. In this review, recent advances of MNs in the treatment of diabetic wound healing are summarized by categorizing the designs and strategies. We finally provide an outlook on the prospects and challenges of MN-based therapies for diabetic wound healing in the future.

Bioactive Composite Cryogels Based on Poly (Vinyl Alcohol) and a Polymacrolactone as Tissue Engineering Scaffolds: In Vitro and In Vivo Studies.

In light of the increasing resistance of pathogenic microorganisms to the action of antibiotics, essential oils extracted from plants with therapeutic activity provide a significant alternative to obtaining dressings for the treatment of skin wounds. The encapsulation of essential oils in an amphiphilic gel network allows better dispersion and preservation of hydrophobic bioactive substances while promoting their prolonged release. In this study, we focused on the development of a poly (vinyl alcohol) (PVA)/poly (ethylene brassylate-co-squaric acid) (PEBSA) platform embedded with thymol (Thy), and α-tocopherol (α-Tcp) as a co-drug structure with prospective use for the treatment and healing of skin wounds. The new complex bioactive system was prepared through repeated freeze-thaw processes. The influence of the composition on surface topography, hydrophilic/hydrophobic character, and in vitro interaction with simulated body fluids was evidenced. BALB/3T3 fibroblast cell culture demonstrated the cryogel scaffolds' cytocompatibility. Tests on Wistar rats confirmed their biocompatibility, integration with host tissue, and the absence of inflammatory processes. The bioactive compound significantly enhanced the healing process of full-thickness excision wounds in a rat model. Further investigations on in vivo infection models would assess the potential of the PVA/PEBSA platform with dual bioactive activity for clinical antimicrobial and wound healing therapy.