Enhanced wound healing potential of arabincoside B isolated from Caralluma Arabica in rat model; a possible dressing in veterinary practice.

BACKGROUND: Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body's cells' alignment to break down due to external assault, such as trauma, burns, accidents, and diseases. Re-epithelization, extracellular matrix deposition, especially collagen, inflammatory cell infiltration, and development of new blood capillaries are the four features that are used to evaluate the healing process. Using a natural extract for wound management is preferred to avoid the side effects of synthetic drugs. The current study aimed to assess the effect of major pregnane glycoside arabincoside B (AR-B) isolated from Caralluma arabica (C. arabica) for the wound healing process. METHOD: AR-B was loaded on a gel for wound application. Rats were randomly distributed into six groups: normal, positive control (PC), MEBO®, AR-B 0.5%, AR-B 1%, and AR-B 1.5%, to be 6 animals in each group. Wounds were initiated under anesthesia with a 1 cm diameter tissue needle, and treatments were applied daily for 14 days. The collected samples were tested for SOD, NO, and MDA. Gene expression of VEGF and Caspase-3. Histopathological evaluation was performed at two-time intervals (7 and 14 days), and immunohistochemistry was done to evaluate α -SMA, TGF-ß, and TNF-α. RESULT: It was found that AR-B treatment enhanced the wound healing process. AR-B treated groups showed reduced MDA and NO in tissue, and SOD activity was increased. Re-epithelization and extracellular matrix deposition were significantly improved, which was confirmed by the increase in TGF-ß and α -SMA as well as increased collagen deposition. TNF-α was reduced, which indicated the subsiding of inflammation. VEGF and Caspase-3 expression were reduced. CONCLUSION: Our findings confirmed the efficiency of AR-B in enhancing the process of wound healing and its potential use as a topical wound dressing in veterinary practice.

Application of metal-organic frameworks in infectious wound healing.

Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.

NIR-responsive electrospun nanofiber dressing promotes diabetic-infected wound healing with programmed combined temperature-coordinated photothermal therapy.

BACKGROUND: Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers. RESULTS: The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds. CONCLUSIONS: The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection.

Concentrated surfactant gel dressing for effective wound healing in pediatric patients: a case series.

BACKGROUND: CSG dressing is water-soluble and helps to hydrate the wound, control exudate, and provide gentle debridement by virtue of a high concentration of surfactant micelles. The primary objective of this retrospective case series is to report on the feasibility of CSG use in pediatric wounds and its mechanism of action. The secondary aim was to measure pain during application and removal of CSG. METHODS: Eight pediatric patients ranging in age from newborn to a few months old with wounds requiring medical intervention were treated with CSG. The CSG dressing was applied twice daily at initiation of treatment in some patients, but mostly once daily. NIPS was utilized for pain measurements. RESULTS: Near-complete healing of wounds was observed by the end of treatment duration, which was only a few days. The calm temperament of these patients during dressing changes and objective NIPS suggested minimal to no pain. None of the patients experienced any adverse events related to the use of this dressing. CONCLUSION: The CSG dressing could be the dressing of choice in this population to enhance debridement and maintain moist healing and support granulation, either proactively or if other treatments fail.

Effects of topical insulin on second-degree burn wound healing: brief report.

BACKGROUND: Burns are classified according to their mechanism of injury, depth, affected body area, affected region or part of the body, and extent of the lesions. Topical insulin modulates the healing process. However, studies evaluating the effects of topical insulin treatment on burns in human patients are lacking. PURPOSE: The purpose of this study was to investigate the effects of topical insulin on healing time of second-degree burns. METHODS: In this nonrandomized clinical trial, patients with second-degree burns were allocated to a control group (CG) or an intervention group (IG) in which wounds were treated with 1% silver sulfadiazine and topical insulin, respectively. RESULTS: Healing time was significantly shorter in the IG relative to the CG (9.1 ± 1.9 days and 12.7 ± 3.3 days, respectively; P < .05). The estimated burn area was similar in both groups (CG 1.44 ± 1.0%; IG 1.42 ± 0.53%). CONCLUSION: In this study, topical insulin reduced healing time in second-degree burns. Further investigation is warranted to support wider use in clinical practice.

Neutrophil extracellular traps-inspired DNA hydrogel for wound hemostatic adjuvant.

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

Dexamethasone treatment influences tendon healing through altered resolution and a direct effect on tendon cells.

Inflammation, corticosteroids, and loading all affect tendon healing, with an interaction between them. However, underlying mechanisms behind the effect of corticosteroids and the interaction with loading remain unclear. The aim of this study was to investigate the role of dexamethasone during tendon healing, including specific effects on tendon cells. Rats (n = 36) were randomized to heavy loading or mild loading, the Achilles tendon was transected, and animals were treated with dexamethasone or saline. Gene and protein analyses of the healing tendon were performed for extracellular matrix-, inflammation-, and tendon cell markers. We further tested specific effects of dexamethasone on tendon cells in vitro. Dexamethasone increased mRNA levels of S100A4 and decreased levels of ACTA2/α-SMA, irrespective of load level. Heavy loading + dexamethasone reduced mRNA levels of FN1 and TenC (p < 0.05), while resolution-related genes were unaltered (p > 0.05). In contrast, mild loading + dexamethasone increased mRNA levels of resolution-related genes ANXA1, MRC1, PDPN, and PTGES (p < 0.03). Altered protein levels were confirmed in tendons with mild loading. Dexamethasone treatment in vitro prevented tendon construct formation, increased mRNA levels of S100A4 and decreased levels of SCX and collagens. Dexamethasone during tendon healing appears to act through immunomodulation by promoting resolution, but also through an effect on tendon cells.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management. Methods: Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats. Results: The PG@PSiSr membranes can afford the sustained release of silicon ions (Si4+) and strontium ions (Sr2+) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.). Conclusion: To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si4+ and Sr2+, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.

Nanomaterial strategies in wound healing: A comprehensive review of nanoparticles, nanofibres and nanosheets.

Wound healing is a complex process that orchestrates the coordinated action of various cells, cytokines and growth factors. Nanotechnology offers exciting new possibilities for enhancing the healing process by providing novel materials and approaches to deliver bioactive molecules to the wound site. This article elucidates recent advancements in utilizing nanoparticles, nanofibres and nanosheets for wound healing. It comprehensively discusses the advantages and limitations of each of these materials, as well as their potential applications in various types of wounds. Each of these materials, despite sharing common properties, can exhibit distinct practical characteristics that render them particularly valuable for healing various types of wounds. In this review, our primary focus is to provide a comprehensive overview of the current state-of-the-art in applying nanoparticles, nanofibres, nanosheets and their combinations to wound healing, serving as a valuable resource to guide researchers in their appropriate utilization of these nanomaterials in wound-healing research. Further studies are necessary to gain insight into the application of this type of nanomaterials in clinical settings.

In vitro experimental conditions and tools can influence the safety and biocompatibility results of antimicrobial electrospun biomaterials for wound healing.

Electrospun (ES) fibrous nanomaterials have been widely investigated as novel biomaterials. These biomaterials have to be safe and biocompatible; hence, they need to be tested for cytotoxicity before being administered to patients. The aim of this study was to develop a suitable and biorelevant in vitro cytotoxicity assay for ES biomaterials (e.g. wound dressings). We compared different in vitro cytotoxicity assays, and our model wound dressing was made from polycaprolactone and polyethylene oxide and contained chloramphenicol as the active pharmaceutical ingredient. Baby Hamster Kidney cells (BHK-21), human primary fibroblasts and MTS assays together with real-time cell analysis were selected. The extract exposure and direct contact safety evaluation setups were tested together with microscopic techniques. We found that while extract exposure assays are suitable for the initial testing, the biocompatibility of the biomaterial is revealed in in vitro direct contact assays where cell interactions with the ES wound dressing are evaluated. We observed significant differences in the experimental outcome, caused by the experimental set up modification such as cell line choice, cell medium and controls used, conducting the phosphate buffer washing step or not. A more detailed technical protocol for the in vitro cytotoxicity assessment of ES wound dressings was developed.

Cell Wall Binding Strategies Based on Cu3SbS3 Nanoparticles for Selective Bacterial Elimination and Promotion of Infected Wound Healing.

Utilizing nanomaterials as an alternative to antibiotics, with a focus on maintaining high biosafety, has emerged as a promising strategy to combat antibiotic resistance. Nevertheless, the challenge lies in the indiscriminate attack of nanomaterials on both bacterial and mammalian cells, which limits their practicality. Herein, Cu3SbS3 nanoparticles (NPs) capable of generating reactive oxygen species (ROS) are discovered to selectively adsorb and eliminate bacteria without causing obvious harm to mammalian cells, thanks to the interaction between O of N-acetylmuramic acid in bacterial cell walls and Cu of the NPs. Coupled with the short diffusion distance of ROS in the surrounding medium, a selective antibacterial effect is achieved. Additionally, the antibacterial mechanism is then identified: Cu3SbS3 NPs catalyze the generation of O2•-, which has subsequently been conversed by superoxide dismutase to H2O2. The latter is secondary catalyzed by the NPs to form •OH and 1O2, initiating an in situ attack on bacteria. This process depletes bacterial glutathione in conjunction with the disruption of the antioxidant defense system of bacteria. Notably, Cu3SbS3 NPs are demonstrated to efficiently impede biofilm formation; thus, a healing of MRSA-infected wounds was promoted. The bacterial cell wall-binding nanoantibacterial agents can be widely expanded through diversified design.

The efficacy of Platelet and Leukocyte Rich Fibrin (L-PRF) in the healing process and bone repair in oral and maxillofacial surgeries: a systematic review.

INTRODUCTION: The search to optimize the healing and bone repair processes in oral and maxillofacial surgeries reflects the constant evolution in clinical practice, driven by the demand for increasingly satisfactory results and the need to minimize postoperative complications. OBJECTIVE: To evaluate the efficacy of Platelet and Leukocyte Rich Fibrin (L-PRF) in the healing and bone repair process in oral and maxillofacial surgeries. MATERIALS AND METHODS: The systematic review protocol for this study included the definition of the research question, the domain of the study, the databases searched, the search strategy, the inclusion and exclusion criteria, the types of studies to be included, the measures of effect, the methods for screening, data extraction and analysis, and the approach to data synthesis. Systematic literature searches were carried out on Cochrane databases, Web of Science, PubMed, ScienceDirect, Embase and Google Scholar. RESULTS: The strategic search in the databases identified 1,159 studies. After removing the duplicates with the Rayyan© software, 946 articles remained. Of these, 30 met the inclusion criteria. After careful evaluation based on the inclusion and exclusion criteria, 8 studies were considered highly relevant and included in the systematic review. CONCLUSION: Platelet and Leukocyte Rich Fibrin (L-PRF) has a positive effect on the healing process and bone repair in oral and maxillofacial surgeries.

Injective hydrogel loaded with liposomes-encapsulated MY-1 promotes wound healing and increases tensile strength by accelerating fibroblast migration via the PI3K/AKT-Rac1 signaling pathway.

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1-34), we previously designed a novel PTH analog, PTH(3-34)(29-34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA-MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.

Effect of Coenzyme Q10 on early wound healing after recession coverage surgery with the modified coronally advanced tunnel technique and a connective tissue graft: A 6-month, triple-blinded, randomized, placebo-controlled pilot trial.

OBJECTIVES: Coenzyme Q10 (CoQ10) or ubiquinone is one of a cell's most important electron carriers during oxidative phosphorylation and many other cellular processes. As a strong anti-oxidant with further anti-inflammatory effects CoQ10 is of potential therapeutical value. The aim of this randomized controlled clinical trial was to investigate the effect of topical CoQ10 on early wound healing after recession coverage surgery using the modified coronally advanced tunnel (MCAT) and palatal connective tissue graft (CTG). MATERIALS AND METHODS: Thirty patients with buccal gingival recessions were evaluated after being randomly allocated to: 1) MCAT and CTG with topical application of a coenzyme Q10 spray for 21 days or 2) MCAT and CTG with placebo spray. Wound healing was evaluated by the early wound healing index (EHI). Patient-reported pain was analyzed by a 100-mm visual analogue scale (VAS) at day 2, 7, 14 and 21 post-surgically. Mean recession coverage, gain of keratinized tissue and esthetic outcomes were assessed at 6 months. RESULTS: EHI and pain scores showed no significant differences. Time to recovery defined as VAS<10 mm was shorter in the test group. Mean root coverage after 6 months was 84.62 ± 26.57% and 72.19 ± 26.30% for test and placebo, p=0.052. Complete root coverage was obtained in 9 (60%) test and in 2 (13.3%) placebo patients. Increase in keratinized tissue width and esthetical outcomes were similar for both groups. CONCLUSION: CoQ10 had no significant effect on early wound healing and on mean root coverage after 6 months. CLINICAL RELEVANCE: Early wound healing: in young healthy patients with no inflammatory oral conditions topical CoQ10 does not improve early healing.

Rose Bengal diacetate-mediated antimicrobial photodynamic inactivation: potentiation by potassium iodide and acceleration of wound healing in MRSA-infected diabetic mice.

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue.

Hair Growth Promoting Effects of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor in Human Follicle Dermal Papilla Cells.

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Portable Photoacoustic Analytical System Combined with Wearable Hydrogel Patch for pH Monitoring in Chronic Wounds.

Timely diagnosis, monitoring, and management of chronic wounds play crucial roles in improving patients' quality of life, but clinical evaluation of chronic wounds is still ambiguous and relies heavily on the experience of clinician, resulting in increased social and financial burden and delay of optimal treatment. During the different stages of the healing process, specific and dynamic changes of pH values in the wound exudate can be used as biomarkers to reflect the wound status. Herein, a pH-responsive agent with well-behaved photoacoustic (PA) properties, nitrazine yellow (NY), was incorporated in poly(vinyl alcohol)/sucrose (PVA/Suc) hydrogel to construct a wearable pH-sensing patch (PVA/Suc/NY hydrogel) for monitoring of pH values during chronic wound healing. According to Rosencwaig-Gersho theory and the combination of 3D printing technology, the PA chamber volume and chopping frequency were systematically optimized to improve the sensitivity of the PA analytical system. The prepared PVA/Suc/NY hydrogel patch had excellent mechanical properties and flexibility and could maintain conformal contact with skin. Moreover, combined with the miniaturized PA analytical device, it had the potential to detect pH values (5.0-9.0) free from the color interference of blood and therapeutic drugs, which provides a valuable strategy for wound pH value monitoring by PA quantitation. This strategy of combining the wearable hydrogel patch with portable PA analysis offers broad new prospects for the treatment and management of chronic wounds due to its features of simple operation, time savings, and anti-interference.

Iron/Molybdenum Sulfide Nanozyme Cocatalytic Fenton Reaction for Photothermal/Chemodynamic Efficient Wound Healing.

The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of antibiotic-resistant strains. Fortunately, the rapid development of nanomaterials has propelled significant progress in antimicrobial therapy, offering promising solutions. Among them, the utilization of nanoenzyme-based chemodynamic therapy (CDT) has become a highly hopeful approach to combating bacterial infectious diseases. Nevertheless, the application of CDT appears to be facing certain constraints for its low efficiency in the Fenton reaction at the infected site. In this study, we have successfully synthesized a versatile nanozyme, which was a composite of molybdenum sulfide (MoS2) and iron sulfide (FeS2), through the hydrothermal method. The results showed that iron/molybdenum sulfide nanozymes (Fe/Mo SNZs) with desirable peroxidase (POD) mimic activity can generate cytotoxic reactive oxygen species (ROS) by successfully triggering the Fenton reaction. The presence of MoS2 significantly accelerates the conversion of Fe2+/Fe3+ through a cocatalytic reaction that involves the participation of redox pairs of Mo4+/Mo6+, thereby enhancing the efficiency of CDT. Additionally, based on the excellent photothermal performance of Fe/Mo SNZs, a near-infrared (NIR) laser was used to induce localized temperature elevation for photothermal therapy (PTT) and enhance the POD-like nanoenzymatic activity. Notably, both in vitro and in vivo results demonstrated that Fe/Mo SNZs with good broad-spectrum antibacterial properties can help eradicate Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococcus aureus. The most exciting thing is that the synergistic PTT/CDT exhibited astonishing antibacterial ability and can achieve complete elimination of bacteria, which promoted wound healing after infection. Overall, this study presents a synergistic PTT/CDT strategy to address antibiotic resistance, providing avenues and directions for enhancing the efficacy of wound healing treatments and offering promising prospects for further clinical use in the near future.

Self-Adapting Biomass Hydrogel Embodied with miRNA Immunoregulation and Long-Term Bacterial Eradiation for Synergistic Chronic Wound Therapy.

Chronic wound rescue is critical for diabetic patients but is challenging to achieve with a specific and long-term strategy. The prolonged bacterial inflammation is particularly prevalent in hyperglycemia-induced wounds, usually leading to severe tissue damage. Such a trend could further suffer from an environmental suitability provided by macrophages for persisting Staphylococcus aureus (S. aureus) and even deteriorate by their mutual reinforcement. However, the strategy of both suppressing bacteria growth and immunoreprogramming the inflammatory type of macrophages to break their vicious harm to wound healing is still lacking. Here, a self-adapting biomass carboxymethyl chitosan (CMC) hydrogel comprising immunomodulatory nanoparticles is reported to achieve Gram-negative/Gram-positive bacteria elimination and anti-inflammatory cytokines induction to ameliorate the cutaneous microenvironment. Mechanistically, antibacterial peptides and CMCs synergistically result in a long-term inhibition against methicillin-resistant S. aureus (MRSA) over a period of 7 days, and miR-301a reprograms the M2 macrophage via the PTEN/PI3Kγ/mTOR signaling pathway, consequently mitigating inflammation and promoting angiogenesis for diabetic wound healing in rats. In this vein, immunoregulatory hydrogel is a promising all-biomass dressing ensuring biocompatibility, providing a perspective to regenerate cutaneous damaged tissue, and repairing chronic wounds on skin.

Screening of the Skin-Regenerative Potential of Antimicrobial Peptides: Clavanin A, Clavanin-MO, and Mastoparan-MO.

Skin wound healing is coordinated by a delicate balance between proinflammatory and anti-inflammatory responses, which can be affected by opportunistic pathogens and metabolic or vascular diseases. Several antimicrobial peptides (AMPs) possess immunomodulatory properties, suggesting their potential to support skin wound healing. Here, we evaluated the proregenerative activity of three recently described AMPs (Clavanin A, Clavanin-MO, and Mastoparan-MO). Human primary dermal fibroblasts (hFibs) were used to determine peptide toxicity and their capacity to induce cell proliferation and migration. Furthermore, mRNA analysis was used to investigate the modulation of genes associated with skin regeneration. Subsequently, the regenerative potential of the peptides was further confirmed using an ex vivo organotypic model of human skin (hOSEC)-based lesion. Our results indicate that the three molecules evaluated in this study have regenerative potential at nontoxic doses (i.e., 200 µM for Clavanin-A and Clavanin-MO, and 6.25 µM for Mastoparan-MO). At these concentrations, all peptides promoted the proliferation and migration of hFibs during in vitro assays. Such processes were accompanied by gene expression signatures related to skin regenerative processes, including significantly higher KI67, HAS2 and CXCR4 mRNA levels induced by Clavanin A and Mastoparan-MO. Such findings translated into significantly accelerated wound healing promoted by both Clavanin A and Mastoparan-MO in hOSEC-based lesions. Overall, the data demonstrate the proregenerative properties of these peptides using human experimental skin models, with Mastoparan-MO and Clavanin A showing much greater potential for inducing wound healing compared to Clavanin-MO.