LSPR-enhanced photoresponsive antibacterial efficiency of Bi/MoS2-loaded fibrin gel for management of diabetic wounds.

Chronic diabetic wounds present formidable challenges, marked by uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The evolving landscape of photo-responsive antibacterial therapy holds great promise in addressing these multifaceted issues, with a particular focus on leveraging the distinctive properties of 2D heterojunction materials. In this investigation, we engineered composite sprayed hydrogels, seamlessly integrating Bi/MoS2 nano-heterojunctions. Capitalizing on the synergistic interplay between photocatalytic antibacterial and photothermal antibacterial mechanisms, the Bi/MoS2 heterojunction, guided by its localized surface plasmon resonance, demonstrated outstanding antibacterial efficacy within a mere 10-minute exposure to 808 nm near-infrared light. This accelerated sterilization both in vitro and in vivo, consequently expediting wound healing. The sprayed composite gel not only furnishes protective shielding for skin tissues but also fosters endothelial cell proliferation, vascularization, and angiogenesis. This safe and ultrafast sterilizing hydrogel presents immense potential for application in antimicrobial dressings, thereby offering a promising avenue for diabetic wound healing.

Clinical efficacy of endovascular revascularization combined with vacuum-assisted closure for the treatment of diabetic foot.

BACKGROUND: The diabetic foot is a common cause of disability and death, and comorbid foot infections usually lead to prolonged hospitalization, high healthcare costs, and a significant increase in amputation rates. And most diabetic foot trauma is complicated by lower extremity arteriopathy, which becomes an independent risk factor for major amputation in diabetic foot patients. AIM: To establish the efficacy and safety of endovascular revascularization (ER) combined with vacuum-assisted closure (VAC) for the treatment of diabetic foot. METHODS: Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022. Diabetic foot lesions were graded according to Wagner's classification, and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries. Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control. Lower limb revascularization was facilitated by percutaneous tran-sluminal balloon angioplasty (BA) or stenting. Wounds were cleaned by nibbling debridement. Wound granulation tissue growth was induced by VAC, and wound repair was performed by skin grafting or skin flap transplantation. RESULTS: Of the 35 cases treated with lower limb revascularization, 34 were successful with a revascularization success rate of 97%. Of these, 6 cases underwent stenting after BA of the superficial femoral artery, and 1 received popliteal artery stent implantation. In the 25 cases treated with infrapopliteal artery revascularization, 39 arteries were reconstructed, 7 of which were treated by drug-coated BA and the remaining 32 with plain old BA. VAC was performed in 32 wounds. Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed. Two patients underwent major amputations, whereas 17 had minor amputations, accounting for a success limb salvage rate of 95%. CONCLUSION: ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates. The use of VAC after ER simplifies and facilitates wound repair.

[Heterogeneous acellular dermal matrix for wound repair after endoscopic Type-â ¤a cordectomy].

Objective:To observe the clinical effect of placing heterogeneous acellular dermal matrix membrane for laryngeal cavity wound healing after CO2 laser Type-Ⅴa cordectomy for glottic carcinoma. Methods:Thirty-five patients with bilateral vocal cord laryngeal cancer who underwent endoscopic CO2 laser surgery at the Department of Otorhinolaryngology Head and Neck Surgery, the Second Xiangya Hospital of Central South University from March 2018 to December 2019 were selected and divided into 2 groups, including 18 patients in the study group and 17 patients in the control group. The control group was simply placed silicone tube stent, while in the study group, heterogeneous acellular dermal matrix membrane was coated with silicone tube stent. The postoperative laryngeal wound repair and clinical manifestations were observed and compared between the two groups. Results:Compared postoperative laryngeal wound after 6 months: no patients in the study group had granulation tissue, whereas 4 patients in the control group had granulation tissue; 3 patients in the study group developed moderate to severe tissue adhesion, while 9 patients in the control group; 10 patients in the control group developed 2nd to 4th degree laryngeal obstruction, compared with only 4 patients in the study group. Conclusion:The primary placement of ADM can reduce laryngeal granulation tissue and tissue adhesion after CO2 laser Type-Ⅴa cordectomy for laryngeal cancer, and may reduce the occurrence of postoperative laryngeal obstruction.

Mechanism of action of montmorillonite powder on injury and repair factors in Stage II pressure ulcers in model mice.

BACKGROUND: This study aims to elucidate the therapeutic effects and underlying mechanisms of montmorillonite powder on wound healing in mice with Stage II pressure ulcers, thereby providing a robust foundation for its clinical application in the treatment of such ulcers. MATERIALS AND METHODS: Sixty 8-week-old specific pathogen-free male BALB/c mice were randomly allocated into three groups: a model group (where Stage II pressure ulcers were induced using the magnet pressure method and the wounds were dressed with gauze soaked in 0.9% sodium chloride solution), a treatment group (where, following the induction of Stage II pressure ulcer models, wounds were uniformly treated with montmorillonite powder), and a control group (where magnets were placed in the same location without exerting magnetic pressure). Skin histopathology was assessed via light microscopy. Wound healing progress over various intervals was quantified utilizing Image-Pro Plus software. Histopathological alterations in the wounds were examined through hematoxylin and eosin (H&E) staining. The expression of growth factor proteins within the wound tissue was analyzed using the streptavidin-peroxidase method. Furthermore, the levels of vascular endothelial growth factor (VEGF), collagen types I and III (COL-I, COL-III) proteins were quantified via Western blotting, serum concentrations of inflammatory mediators in mice were determined by enzyme-linked immunosorbent assay, and the levels of oxidative stress markers in wound tissues were measured using UV-visible spectrophotometry. RESULTS: The treatment group exhibited significantly reduced serum levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-alpha, and elevated levels of interleukin-4 compared to the model group (p < 0.05). Additionally, the expression of transforming growth factor-beta1, basic fibroblast growth factor, epidermal growth factor, VEGF, COL-I, and COL-III proteins in wound tissues was significantly higher in the treatment group than in the model group (p < 0.05). Levels of superoxide dismutase and glutathione peroxidase in wound tissues were higher, and levels of malondialdehyde were lower in the treatment group compared to the model group (p < 0.05). CONCLUSION: Montmorillonite powder facilitates wound healing and augments the healing rate of Stage II pressure ulcers in model mice. Its mechanism of action is likely associated with mitigating wound inflammation, reducing oxidative stress damage, promoting angiogenesis, and enhancing the synthesis of growth factors and collagen.

[Clinical application of perforator-based propeller flaps in repair of hand wound].

Objective: To investigate the effectiveness of the perforator-based propeller flaps (PPFs) based on digital artery (DA) and dorsal metacarpal artery (DMA) in repairing hand wounds. Methods: The clinical data of 45 patients with hand wounds between January 2018 and March 2023 were retrospectively analyzed. There were 27 males and 18 females with an average age of 41.2 years (range, 14-72 years). The causes of injury included twist injury in 15 cases, crush injury in 19 cases, and cut injury in 11 cases. The injured parts included 32 cases of digits, 10 cases of dorsal hand, and 3 cases of palmar hand, all of which had tendon, joint, and bone exposure. The time from injury to operation ranged from 2 to 8 hours (mean, 4.3 hours). The wound sizes after debridement ranged from 1.8 cm×1.0 cm to 5.0 cm×3.5 cm. Twenty-eight cases were repaired by the PPFs based on DA and 17 cases were repaired by the PPFs based on DMA. The flap size ranged from 2.5 cm×1.1 cm to 8.5 cm×4.0 cm. The defects of the donor sites in 14 patients were closed directly and the defects in the left 31 patients were resurfaced with free full-thickness skin graft from the proximal medial forearm. Results: All the flaps survived after operation. Two cases of the PPF based on DA and 1 case of the PPF based on DMA underwent partially blisters at the distal end and healed after dressing change. The incisions in the donor site healed by first intention and the skin grafts survived. All patients were followed up 10-33 months, with a mean of 15.4 months. At last follow-up, the static two-point discrimination of the PPFs based on DA and DMA were 4-14 mm and 8-20 mm with the averages of 8.1 mm and 13.3 mm, respectively. According to the Michigan Hand Outcomes Questionnaire, 20 patients were very satisfied with the appearance of the PPF based on DA and 8 patients were satisfied; 8 patients were very satisfied with the appearance of the PPF based on DMA and 9 patients were satisfied. Based on the Vancouver Scar Scale (VSS), the appearance scores of the donor site of the PPFs based on DA and DMA were 2-7 and 4-9, with the averages of 4.2 and 6.1, respectively. Conclusion: The two kinds of PPFs are reliable in blood supply and easy to harvest, which provide a good method for emergency repair of small and medium area wounds in the hand.

Antibacterial and antioxidant phlorizin-loaded nanofiber film effectively promotes the healing of burn wounds.

Burns usually result in damage and loss of skin forming irregular wound wounds. The lack of skin tissue protection makes the wound site highly vulnerable to bacterial infections, hindering the healing process. However, commonly used wound dressings do not readily provide complete coverage of irregular wounds compared to regular wounds. Therefore, there is an urgent need to prepare a wound dressing with high antimicrobial efficacy for the administration of drugs to irregular wounds. In this study, a chitosan (CS)/polyvinylpyrrolidone (PVP) composite nanofiber membrane (CS/PVP/Phlorizin) loaded with root bark glycosides (Phlorizin) was developed using an electrostatic spinning technique. The incorporation of phlorizin, a natural antioxidant, into the fiber membranes notably boosted their antimicrobial and antioxidant capabilities, along with demonstrating excellent hydrophilic characteristics. In vitro cellular experiments showed that CS/PVP/Phlorizin increased Hacat cell viability with the presence of better cytocompatibility. In scald wound healing experiments, Phlorizin-loaded nanofibrous membranes significantly promoted re-epithelialization and angiogenesis at the wound site, and reduced the inflammatory response at the wound site. Therefore, the above results indicate that this nanofiber membrane is expected to be an ideal dressing for burn wounds.

Exploring the potential mechanisms of the ethyl acetate fraction of Hippophae rhamnoides L. seeds as a natural healing agent for wound repair.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides L.) has been designated a "medicine food homology" fruit by the National Health Commission of China due to its nutritional value. In traditional Chinese ethnomedicine, Hippophae rhamnoides L. is commonly used to treat nonhealing wounds such as burns, sores, and gastric ulcers. The aim of this study was to explore the healing effects of the ethyl acetate extract of sea buckthorn seeds (SBS-EF) on burn wounds. AIM OF THE STUDY: The primary objectives of this research were to determine the most effective medicinal site of action for treating burns with sea buckthorn seeds (SBS) and to investigate the underlying material basis and mechanisms of their therapeutic effects. MATERIALS AND METHODS: The effects of different components of SBS-EF on the proliferation and migration of human skin fibroblasts (HSFs) were evaluated via MTT assays, scratch assays, transwell assays, and hydroxyproline secretion analysis. SBS-EF displayed the greatest activity amongst the extracts. Subsequent analyses included network pharmacology methodology, molecular docking studies, ultraperformance liquid chromatography UPLC-Orbitrap-Exploris-120-MS and a severe second-degree burn rat model to investigate the chemical constituents and potential therapeutic mechanisms of the SBS-EF. RESULTS: In vitro studies demonstrated the efficacy of SBS-EF in promoting HSF growth and migration. UPLC-Orbitrap-Exploris-120-MS analysis revealed that SBS-EF had ten major constituents, with flavonoids being the predominant compounds, especially catechin, quercetin, and kaempferol derivatives. Network pharmacology and molecular docking analyses indicated that SBS-EF may exert its healing effects by modulating the Wnt/ß-catenin signalling pathway. Subsequent in vivo experiments demonstrated that SBS-EF accelerated burn wound healing in rats, increased hydroxyproline expression in skin tissue, facilitated skin structure repair, and enhanced collagen production and organisation over a 21 d period. Additionally, exposure to SBS-EF upregulated WNT3a and ß-catenin while downregulating GSK-3ß levels in rat skin tissue. CONCLUSIONS: The wound healing properties of SBS-EF were attributed to its ability to enhance HSF growth and migration, increase hydroxyproline levels in the skin, promote collagen accumulation, reduce scarring, and decrease the skin water content. SBS-EF may also provide therapeutic benefits for burns by modulating the Wnt/ß-catenin signalling pathway, as evidenced by its effective site and likely mechanism of action in the treatment of burned rats.

Angiogenesis and full thickness wound repair in a cell sheet-based vascularized skin substitute.

Skin tissue engineering is undergoing tremendous expansion as a result from clinical needs, mandatory replacement of animal models and development of new technologies. Many approaches have been used to produce vascularized skin substitutes for grafting purposes showing the presence of capillary-like structures but with limited analysis of their in vitro maturation and plasticity. Such knowledge is however important for the development of tissue substitutes with improved implantation success as well as for validation of vascularization in vitro models, including as a readout in pharmacological analyses. For optimal interactions of cells with microenvironment and vasculature, we here used a cell sheet approach consisting in the sole production of matrix by the cells. In this context, we limited the density of endothelial cells seeded for self-assembly and rather relied on the stimulation of angiogenesis for the development of an extensive connected microvascular-like network. After detailed characterization of this network, we challenged its plasticity both during and after establishment of the skin substitute. We show that fine tuning of VEGF concentration and time of application differentially affects formation of capillary-like structures and their perivascular coverage. Furthermore, we performed a deep wound assay that displayed tissue repair and angiogenesis with unique characteristics of the physiological process. These studies demonstrate the importance of cell-derived microenvironment for the establishment of mature yet dynamic vascularized skin models allowing a wide range of pharmacological and basic investigations. STATEMENT OF SIGNIFICANCE: The significant advancements in organ-on-chips and tissue engineering call for more relevant models including microvascularization with remodeling potential. While vascularized skin substitutes have been developed for years, focus has primarily been on the impact of microvascularization on implantation rather than on its in vitro characterization. We here developed a cell sheet-based vascularized skin substitute relying on angiogenesis, i.e. growth of vessel-like structures within the 3D model, rather than solely on endothelial cell self-assembly. We then characterized :1/ vascularization after modulation of angiogenic factor VEGF during the substitute construction; -2/ angiogenesis associated to tissue repair after deep mechanical wounding. These studies establish a solid physiologically relevant model for further investigation of skin cell interactions and in vitro wound healing.

The Horizons of Medical Mineralogy: Structure-Bioactivity Relationship and Biomedical Applications of Halloysite Nanoclay.

Medical mineralogy explores the interactions between natural minerals and living organisms such as cells, tissues, and organs and develops therapeutic and diagnostic applications in drug delivery, medical devices, and healthcare materials. Many minerals (especially clays) have been recognized for pharmacological activities and therapeutic potential. Halloysite clay (Chinese medicine name: Chishizhi), manifested as one-dimensional aluminum silicate nanotubes (halloysite nanotubes, HNTs), has gained applications in hemostasis, wound repair, gastrointestinal diseases, tissue engineering, detection and sensing, cosmetics, and daily chemicals formulations. Various biomedical applications of HNTs are derived from hollow tubular structures, high mechanical strength, good biocompatibility, bioactivity, and unique surface characteristics. This natural nanomaterial is safe, abundantly available, and may be processed with environmentally safe green chemistry methods. This review describes the structure and physicochemical properties of HNTs relative to bioactivity. We discuss surface area, porosity and surface defects, hydrophilicity, heterogeneity and charge of external and internal surfaces, as well as biosafety. The paper provides comprehensive guidance for the development of this tubule nanoclay and its advanced biomedical applications for clinical diagnosis and therapy.

Cellular In Vitro Responses Induced by Human Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Obtained from Suspension Culture.

Mesenchymal stem/stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have been described to have important roles in tissue regeneration, including tissue repair, control of inflammation, enhancing angiogenesis, and regulating extracellular matrix remodeling. MSC-EVs have many advantages for use in regeneration therapies such as facility for dosage, histocompatibility, and low immunogenicity, thus possessing a lower possibility of rejection. In this work, we address the potential activity of MSC-EVs isolated from adipose-derived MSCs (ADMSC-EVs) cultured on cross-linked dextran microcarriers, applied to test the scalability and reproducibility of EV production. Isolated ADMSC-EVs were added into cultured human dermal fibroblasts (NHDF-1), keratinocytes (HaCat), endothelial cells (HUVEC), and THP-1 cell-derived macrophages to evaluate cellular responses (i.e., cell proliferation, cell migration, angiogenesis induction, and macrophage phenotype-switching). ADMSC viability and phenotype were assessed during cell culture and isolated ADMSC-EVs were monitored by nanotracking particle analysis, electron microscopy, and immunophenotyping. We observed an enhancement of HaCat proliferation; NHDF-1 and HaCat migration; endothelial tube formation on HUVEC; and the expression of inflammatory cytokines in THP-1-derived macrophages. The increased expression of TGF-ß and IL-1ß was observed in M1 macrophages treated with higher doses of ADMSC-EVs. Hence, EVs from microcarrier-cultivated ADMSCs are shown to modulate cell behavior, being able to induce skin tissue related cells to migrate and proliferate as well as stimulate angiogenesis and cause balance between pro- and anti-inflammatory responses in macrophages. Based on these findings, we suggest that the isolation of EVs from ADMSC suspension cultures makes it possible to induce in vitro cellular responses of interest and obtain sufficient particle numbers for the development of in vivo concept tests for tissue regeneration studies.

Review of Malaysian medicinal plants with potential wound healing activity.

Wound is defined as the damage to biological tissues including skin, mucous membranes and organ tissues. The acute wound heals in less than 4 weeks without complications, while a chronic wound takes longer than 6 weeks to heal. Wound healing occurs in 4 phases, namely, coagulation, inflammatory, proliferative and remodeling phases. Triclosan and benzalkonium chloride are commonly used as skin disinfectants in wound healing. However, they cause allergic contact dermatitis and antibiotic resistance. Medicinal plants are widely studied due to the limited availability of wound healing agents. The present review included six commonly available medicinal plants in Malaysia such as Aloe barbadensis Miller, Carica papaya Linn., Centella asiatica Linn., Cymbopogon nardus Linn., Ficus benghalensis Linn. and Hibiscus rosa sinensis Linn. Various search engines and databases were used to obtain the scientific findings, including Google Scholar, ScienceDirect, PubMed Central and Research Gate. The review discussed the possible mechanism of action of medicinal plants and their active constituents in the wound healing process. In addition, their application in nanotechnology and wound dressings was also discussed in detail.

Early versus Delayed Vitrectomy for Open Globe Injuries: A Systematic Review and Meta-Analysis.

Background: Open globe injuries (OGIs) are a leading cause of monocular blindness worldwide and require prompt intervention to prevent proliferative vitreoretinopathy (PVR) and endophthalmitis when serious intraocular damage occurs. The management of OGIs involves initial wound closure within 24 hours, followed by vitrectomy as a secondary surgery. However, there is a lack of consensus regarding the optimal timing of vitrectomy for maximizing visual outcomes. This meta-analysis aimed to investigate whether early or delayed vitrectomy leads to better outcomes in patients with OGIs. Methods: This review was conducted based on PRISMA guidelines. The Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched (October 23, 2023). Clinical studies that used vitrectomy to manage OGIs as early (within 7 days) or delayed (8-14 days) interventions were included. Randomized controlled trials (RCTs) and non-RCTs were appraised using the Cochrane risk of bias and JBI tools, respectively. Results: Eleven studies met the inclusion criteria and were included in the quantitative analyses. There were 235 patients with OGIs who received early intervention and 211 patients who received delayed intervention. The retina was reattached in 91% and 76% of the patients after early and delayed intervention, respectively. Traumatic PVR was present in 9% and 41% of the patients in the early and delayed groups, respectively. The odds of retinal reattachment after vitrectomy were greater in the early group (OR = 3.42, p = 0.010, 95% CI=1.34-8.72), and the odds of visual acuity ≥ 5/200 were 2.4 times greater in the early group. The incidence of PVR was significantly greater in the delayed surgery group (OR = 0.16, p < 0.0001; 95% CI=0.06-0.39), which also required more than one vitrectomy surgery. Conclusion: Early vitrectomy results in better postoperative visual acuity, a greater proportion of retinal reattachment, and a decreased incidence of PVR.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats.

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.

Calcium influx rapidly establishes distinct spatial recruitments of Annexins to cell wounds.

To survive daily damage, the formation of actomyosin ring at the wound edge is required to rapidly close cell wounds. Calcium influx is one of the start signals for these cell wound repair events. Here, we find that the rapid recruitment of all 3 Drosophila calcium-responding and phospholipid-binding Annexin proteins (AnxB9, AnxB10, and AnxB11) to distinct regions around the wound is regulated by the quantity of calcium influx rather than their binding to specific phospholipids. The distinct recruitment patterns of these Annexins regulate the subsequent recruitment of RhoGEF2 and RhoGEF3 through actin stabilization to form a robust actomyosin ring. Surprisingly, while the wound does not close in the absence of calcium influx, we find that reduced calcium influx can still initiate repair processes, albeit leading to severe repair phenotypes. Thus, our results suggest that, in addition to initiating repair events, the quantity of calcium influx is important for precise Annexin spatiotemporal protein recruitment to cell wounds and efficient wound repair.

Tranexamic acid-loaded catechol-modified hyaluronic acid/carboxymethyl chitosan double cross-linked porous gel micropowders for rapid hemostasis and wound healing.

Acquiring rapid and effective hemostasis remains a critical clinical challenge. Current researches focus on concentrating blood components to speed up the hemostatic while ignore the effect of anti-fibrinolysis in promoting blood coagulation. Herein, we designed a novel tranexamic acid (TA)-loaded physicochemical double cross-linked multifunctional catechol-modified hyaluronic acid-dopamine/carboxymethyl chitosan porous gel micropowders (TA&Fe3+@HA-DA/CMCS PGMs) for rapid hemostasis and wound healing. TA&Fe3+@HA-DA/CMCS PGMs exhibited high water absorption rate (505.9 ± 62.1 %) and rapid hemostasis (79 ± 4 s) in vivo. Catechol groups, Fe3+ and the protonated amino groups of CMCS induced bacterial death. Moreover, TA&Fe3+@HA-DA/CMCS PGMs displayed sufficient adhesion to a variety of wet rat tissues. TA&Fe3+@HA-DA/CMCS PGMs on various bleeding wounds, including rat liver injury and tail severed models showed excellent hemostasis performance. The TA&Fe3+@HA-DA/CMCS PGMs could promote the healing of full-thickness skin wounds on the backs of rats. The advantages of TA&Fe3+@HA-DA/CMCS PGMs including rapid hemostasis, effective wound healing, good tissue adhesion, antibacterial properties and ease of use make it potentially valuable in clinical application.

Prussian Blue-Assisted NIR Triggered In-Situ Polymerized Nanocomposite Hydrogel for Wound Repair.

Hydrogels are commonly used as wound dressings to help maintain a moist environment around the wound and isolate contaminants, thus promoting healing. For irregular wounds, the slow healing process and even infection may occur due to the inability of dressings to adhere well to the wound. Prussian blue (PB) is a metal-organic framework (MOF) material with excellent photothermal conversion and superior stability. In this paper, a kind of near-infrared (NIR) light triggered in-situ polymerized antimicrobial hydrogel was prepared. The free radical initiator was encapsulated in the hollow PB by a phase change material (PCM) to maintain stability. The raised temperature triggered by NIR induced the release and decomposition of the initiator. The matrix was formed by the cross-linking of double bonds on modified chitosan. The quaternary amine groups of modified chitosan and the photothermal properties of PB enhanced the antimicrobial properties of the hydrogel. High-quality wound healing was demonstrated in the whole skin defect model. This study provides a new reference for the preparation of in-situ polymerized hydrogel dressings for irregular wounds.

Altering CO2 Laser Pulse Energy Settings Did Not Influence Differential Gene Transcription in Normal Skin in a Red Duroc Pig Model.

OBJECTIVES: Fractional ablative CO2 lasers are used clinically to treat cutaneous burn scars with reported varying degrees of effectiveness. It was hypothesized that different laser pulse energy settings may lead to differential gene transcription in a porcine model. METHODS: Uninjured skin from red Duroc pigs was treated with a fractional ablative CO2 laser set to 70, 100, or 120 mJ across the abdomen (n = 4 areas per treatment). Punch biopsies of both treated and untreated sites were taken before treatment (baseline), at 30 min, and at each hour for 6 h and stored in All-Protect tissue reagent. The biopsies were then used to isolate RNA, which was subsequently used in qRT-PCR for eight genes associated with wound healing and the extracellular matrix: CCL2, IL6, FGF2, TIMP1, TIMP3, COL1A2, MMP2, and DCN. RPL13a was used as a housekeeping gene to normalize the eight genes of interest. One-way ANOVA tests were used to assess for differences among laser pulse energies and two-way ANOVA tests were used to assess the differences between treated and untreated areas. RESULTS: While six of the eight genes were upregulated after treatment (p < 0.05), there were no significant differences in gene expression between the different laser pulse energies for any of the eight genes. CONCLUSION: While laser treatment is correlated with a positive and significant upregulation for six of the eight genes 4 h after intervention, the pulse energy settings of the laser did not lead to a statistically significant difference in gene transcription among the treatment areas. Different laser pulse energies may not be required to induce similar cellular responses in a clinical setting.

Long duration sodium hyaluronate hydrogel with dual functions of both growth prompting and acid-triggered antibacterial activity for bacteria-infected wound healing.

Conventional wound dressings are monolithically designed to cover the injured areas as well as absorb the exudates at injured site. Furthermore, antibacterial drugs and growth prompting factors are additionally appended to realize sensible and omnibearing wound management, exhibiting long and tedious treatment process in practice. Consequently, the creation of multifunctional wound dressings that combines wound repair enhancement with antibacterial properties turns out to be significant for simplifying wound managements. In our investigation, electronegative human epidermal growth factor (hEGF) was combined with the positively charged Zn-Al layered double hydroxides (Zn-Al LDHs) via electrostatic interaction while the obtained hEGF/LDH was integrated with sodium hyaluronate hydrogel (SH) hydrogel, forming a composite hydrogel with synergistic benefits for wound management. The innovative hEGF/LDH@SH hydrogel equipped with fine biocompatibility was designed to optimize wound healing in which hEGF stimulates epithelial cell growth while LDH released antibacterial factor Zn2+ against Methicillin-resistant staphylococcus aureus (MRSA) and Escherichia coli (E.coli) under acidic wound environment. Additionally, the SH hydrogel constructed a three-dimensional structure that not only safeguarded the wound area but also maintained a moist environment conducive to recovery. The synthesized hEGF/LDH was confirmed via fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and thermo-gravimetry (TG) measurements. The release of Zn2+ from Zn-Al LDH under acid circumstance was detected via inductively coupled plasma (ICP) and the in vitro bactericidal experiments endowed the antibacterial property of hEGF/LDH@SH hydrogel. In vitro drug release experiments illustrated the controlled-release of hEGF from hEGF/LDH which promoted the long-term affect of hEGF at wound site. In vitro cell experiments verified that the hEGF/LDH@SH hydrogel motivated the promotion on cell proliferation and migration without cytotoxicity. An in vivo study of the repairing of MRSA-infected wound in mice indicated that hEGF/LDH@SH hydrogel serves as a simple and novel, innoxious and efficient wound healing approach. This brand new hydrogel possesses properties of promoting the regeneration of skin tissue, achieving antimicrobial therapy without any accessional antibacterial drugs as well as realizing controlled release of hEGF.

Bioactive Metal Ion-Coordinated Dynamic Hydrogel with Antibacterial, Immunomodulatory, and Angiogenic Activities for Infected Wound Repair.

The repair of infected wounds is a complex physiopathologic process. Current studies on infected wound treatment have predominantly focused on infection treatment, while the factors related to delayed healing caused by vascular damage and immune imbalance are commonly overlooked. In this study, an extracellular matrix (ECM)-like dynamic and multifunctional hyaluronic acid (HA) hydrogel with antimicrobial, immunomodulatory, and angiogenic capabilities was designed as wound dressing for the treatment of infected skin wounds. The dynamic network in the hydrogel dressing was based on reversible metal-ligand coordination formed between sulfhydryl groups and bioactive metal ions. In our design, antibacterial silver and immunomodulatory zinc ions were employed to coordinate with sulfhydrylated HA and a vasculogenic peptide. In addition to the desired bioactivities for infected wounds, the hydrogel could also exhibit self-healing and injectable abilities. Animal experiments with infected skin wound models indicated that the hydrogel dressings enabled minimally invasive injection and seamless skin wound covering and then facilitated wound healing by efficient bacterial killing, continuous inflammation inhibition, and improved blood vessel formation. In conclusion, the metal ion-coordinated hydrogels with wound-infection-desired bioactivities and ECM-like dynamic structures represent a class of tissue bionic wound dressings for the treatment of infected and chronic inflammation wounds.

Tracing Immunological Interaction in Trimethylamine N-Oxide Hydrogel-Derived Zwitterionic Microenvironment During Promoted Diabetic Wound Regeneration.

The diabetic wound healing is challenging due to the sabotaged delicate balance of immune regulation via an undetermined pathophysiological mechanism, so it is crucial to decipher multicellular signatures underlying diabetic wound healing and seek therapeutic strategies. Here, this work develops a strategy using novel trimethylamine N-oxide (TMAO)-derived zwitterionic hydrogel to promote diabetic wound healing, and explore the multi-cellular ecosystem around zwitterionic hydrogel, mapping out an overview of different cells in the zwitterionic microenvironment by single-cell RNA sequencing. The diverse cellular heterogeneity is revealed, highlighting the critical role of macrophage and neutrophils in managing diabetic wound healing. It is found that polyzwitterionic hydrogel can upregulate Ccl3+ macrophages and downregulate S100a9+ neutrophils and facilitate their interactions compared with polyanionic and polycationic hydrogels, validating the underlying effect of zwitterionic microenvironment on the activation of adaptive immune system. Moreover, zwitterionic hydrogel inhibits the formation of neutrophil extracellular traps (NETs) and promotes angiogenesis, thus improving diabetic wound healing. These findings expand the horizons of the sophisticated orchestration of immune systems in zwitterion-directed diabetic wound repair and uncover new strategies of novel immunoregulatory biomaterials.