Promote Wound Healing Research Articles

Smart chitosan-based nanofibers for real-time monitoring and promotion of wound healing

Timely healing of acute wounds and stopping wound chronicity are current and future priorities in wound therapy. It is urgent and relevant to develop a wound dressing that has antimicrobial and monitors the wound microenvironment in real time. In this study, quaternary ammonium chitosan (HTCC) was selected as the antimicrobial agent and CS/PEO/HTCC nanofiber membranes (CPHs) were prepared by electrostatic spinning technique. The nanofiber membrane (CPH91) with the best antimicrobial performance was screened by the disk diffusion method and drug susceptibility testing by dilution method, and its antimicrobial effect on S. aureus was better than that of E. coli. Subsequently, functional carbon dots (CDs) were synthesized by solvothermal method and doped into CPH91 nanofibers by electrospinning. A good linear relationship between pH value (5.0–8.0) and the fluorescence intensity of CDs was observed. In addition, the nanofibers (CPH91@CDs) had good morphology, hydrophilicity, and biocompatibility. Changes in fluorescence intensity of CPH91@CDs at different pH (5.0–8.0) were monitored and converted into RGB values that were linearly fitted to pH value. Finally, the potential of CPH91@CDs of improving wound healing and instantaneously controlling wound healing process was confirmed by an infected wound model (S. aureus) on the back of SD rats.

Copper peroxide-decorated Prussian blue for effective bacterial elimination via photothermal-enhanced and H2O2-releasing chemodynamic therapy

Bacterial infection is a major impediment towards wound healing and threaten human health worldwide. Traditional antibiotic therapy poses a high risk of inducing bacterial resistance, thus nanomaterial-based synergistic bactericidal strategy as effective alternatives have received tremendous attention. Herein, a NIR/pH-dual responsive nanoplatform was fabricated for synergistic photothermal and chemodynamic therapy (PTT/CDT). Prussian blue (PB) were employed as supporting material, while copper peroxide (CP) were growth in situ on PB surface, resulting in a core-shell structured nanoplatform (designated as PC). PB core served as photothermal/Fenton catalyst dual agents, and CP shell could co-release Cu2+ and H2O2 under acidic bacterial infection environment, realizing synergistic PTT and H2O2-releasing CDT. Under NIR irradiation, PC exhibited photothermal-enhanced Fenton-like reaction feature and the hyperthermia facilitated Cu2+ release, leading to the rapid conversion of H2O2 into toxic •OH to effectively kill Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), eradicating S. aureus biofilm. Moreover, the released Cu2+ could improve the bactericidal effect of CDT via the depletion of GSH and significantly promote cell migration. Furthermore, in vivo experiments demonstrated PC with good biocompatibility exhibited robust bactericidal effect and promoted wound healing. Overall, this versatile nanoplatform offered an efficacious and safe antibiotic-free strategy for bacterial infection treatments.

A Review on Nanocarrier-based Polyherbal Drug Delivery Systems for Wound Healing

Background: Nanotechnology-based polyherbal drug delivery systems are considered a new and rapidly emerging area in the pharmaceutical field. They improved the drug loading capacity or enhanced encapsulation efficiency of herbal drugs and thus improved permeation efficiency, accelerated wound healing, promoted tissue remodelling, and reduced scarring. Objective: A wound on the skin is an injury of the skin tissues that arises due to a cut or damage and also by an impact, blow, or other forces like a cut, surgery, chemical, heat, cold, friction, or illness like leg ulcers or carcinomas. These wounds result in the loss of skin's protective function by the removal of epithelium or connective tissues (i.e., muscle, bone, nerves). The four sequential but overlapping phases of the typical wound healing process are hemostasis, inflammation, proliferation, and remodeling. By encouraging the growth and movement of fibroblasts and keratinocytes, as well as angiogenesis at the site of damage, it has been demonstrated that a polyherbal mixture composed of plant extraction accelerates the lesion recovery process. Polyherbal formulations contain phytoconstituents such as triterpenoids, flavonoids, coumarins, quinones, and carotenoids etc. All these phytoconstituents are used for anti-inflammatory, anti-microbial, antioxidant, and lesion recovery. At the same time, nanotechnology-based polyherbal formulation has the potential to overcome the limitations of traditional polyherbal formulation in wound healing. Wounds are better managed by polyherbal combination rather than an individual plant due to its synergism and fewer side effects. To include these polyherbal components and deliver them to the wound site in a more focused and sustained way, novel drug delivery systems are also being developed. Conclusion: This review discussed many nanotechnology-based polyherbal topical formulations for efficient and faster wound healing and recovery. Nanotechnology-based polyherbal formulations prove their success in promoting wound healing which is a unique approach to improving wound care and development of healthy skin.

Demonstrating the potential of bioactive glass-infused electrospun PVB fibrous patches in atopic dermatitis moisturizing therapy

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by pruritic and eczematous lesions. Current treatment modalities often focus on symptomatic relief through topical moisturizers to restore impaired skin barrier function. Bioactive glasses, such as 45S5 and 59S compositions, have gained attention for their potential therapeutic applications in dermatological conditions due to their biocompatibility, bioactivity, and ability to promote wound healing. In this study, we explore the feasibility and efficacy of utilizing electrospun polyvinyl butyral (PVB) fibrous patches infused with bioactive glass particles as a novel approach for moisturizing therapy in AD. The electrospun PVB fibrous patches were fabricated through a simple and scalable electrospinning technique, incorporating bioactive glass particles. Physicochemical properties, including morphology, mechanical strength, and bioactive properties, were characterized using scanning electron microscopy (SEM), tensile testing, and in- vitro bioactivity. Additionally, the protein absorption kinetics of the fibrous patches were evaluated. Furthermore, in-vitro hemocompatibility, cell viability studies and live/dead assay were conducted to assess the biocompatibility of the bioactive glass-infused PVB fibrous patches. Our findings demonstrate that the incorporation of bioactive glass particles into electrospun PVB fibrous patches confers enhanced mechanical properties and sustained release of bioactive ions, providing a promising platform for prolonged moisturizing therapy.

Smart copper-doped clays in biomimetic microparticles for wound healing and infection control

Chronic wounds are non-healing lesions characterized by a high degree of inflammation, posing significant challenges in clinical management due to the increased risk of severe infection. This study focuses on developing a powder for cutaneous application to enhance healing and prevent infections in chronic wounds. The smart nanocomposite-based biomimetic microparticles here developed combine the properties of chitosan and of clays and represent a significant innovation in the field of biomaterials for skin regeneration since they possess enhanced antimicrobial properties, are multi-functional scaffolds and promote cell proliferation, support tissue reconstruction by mimicking the natural extracellular matrix, and provide hemostatic properties to control bleeding during wound closure. The microparticles were made of chitosan and doped with clay minerals, specifically montmorillonite or layered double hydroxides containing copper ions. The synergistic combination of biomimetic polymers and clays aims to regulate cellular responses, angiogenesis, and extracellular matrix (ECM) deposition, leveraging the bioactive properties of both components to promote wound healing. Montmorillonite and layered double hydroxides were enriched with copper ions through intercalation or coprecipitation methods, respectively. The water-insoluble microparticles were prepared using a chitosan derivative, chitosan carbamate, synthesized to obtain chitosan-based microparticles via spray-drying without crosslinkers. Physico-chemical characterization confirmed the successful doping of Cu-clay interaction products in the microparticles. In addition to enhanced cell proliferation and haemostatic properties, the presence of Cu-clays boosted the microparticles’ antibacterial properties. Encouraging preclinical in vitro and in vivo results suggest that these smart nanocomposite biomimetic microparticles doped with Cu-enriched clay minerals could be promising candidates for simultaneously enhancing healing and controlling infections in chronic wounds.

Electrospinning drug-loaded polycaprolactone/polycaprolactone-gelatin multi-functional bilayer nanofibers composite scaffold for postoperative wound healing of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) tumor resection surgery poses challenges due to incomplete cancer cell removal, which increases the risk of local recurrence and micrometastasis, while large-scale surgical wounds are susceptible to severe infections. Therefore, a drug-loaded multi-functional bilayer nanofibers skin scaffold was fabricated for postoperative wound care of cSCC. Briefly, the antibacterial drug enrofloxacin (ENR) was loaded into polycaprolactone (PCL) nanofibers using electrospinning to form an antibacterial nanofiber membrane (PCL-ENR) as the outer layer of scaffold. The anticancer drug bleomycin (BLM) was loaded into PCL/Gelatin (Gel) nanofibers via electrospinning to form an anticancer nanofiber membrane (PG-BLM) as the inner layer of scaffold. ENR and BLM were successfully loaded into the scaffold. The scaffold had excellent physicochemical properties, with the outer layer exhibiting hydrophobicity and excellent antibacterial activity, and the inner layer showing hydrophilicity and outstanding anticancer activity. The elongation at break and tensile modulus of the scaffold were 26.35 ​± ​1.61 ​% and 15.25 ​± ​1.56 ​MPa, respectively. In vitro and in vivo experiments suggested that the scaffold not only has good biocompatibility to promote wound healing but also could inhibit the proliferation of A431 ​cells, which has great potential clinical application in postoperative wound care of cSCC.

Spinal cord stimulation induces Neurotrophin-3 to improve diabetic foot disease.

Low-extremity ischemic disease is a common complication in diabetic patients, leading to reduced quality of life and potential amputation. This study investigated the therapeutic effect of spinal cord stimulation (SCS) on patients with diabetic foot disease and a rat model of diabetic foot injury. SCS was applied to patients with diabetic foot disease, with clinical assessments performed before and after therapy. Blood levels of NGF, BDNF, and NT-3 were determined by ELISA. A rat model of diabetic foot injury was established to validate NT-3's role in SCS therapy. SCS therapy improved the condition of patients with diabetic ischemic foot disease and promoted wound healing in the rat model. NT-3 levels significantly increased after SCS therapy in both patients and rats. Recombinant NT-3 administration improved wound healing and re-vascularization in the rat model, while NT-3 neutralization abrogated SCS's therapeutic effect. SCS improves the condition of patients with diabetic ischemic foot disease by inducing NT-3 production. Both SCS and NT-3 supplementation show therapeutic potential for ameliorating diabetic foot disease.

LysSYL-Loaded pH-Switchable Self-Assembling Peptide Hydrogels Promote Methicillin-Resistant Staphylococcus Aureus Elimination and Wound Healing.

Staphylococcus aureus (S. aureus), especially methicillin-resistant S. aureus (MRSA), causes wound infections, whose treatment remains a clinical challenge. Bacterium-infected wounds often create acidic niches with a pH 4.5-6.5. Endolysin LysSYL, which is derived from phage SYL, shows promise as an antistaphylococcal agent. However, endolysins generally exhibit instability and possess low bioavailability in acidic microenvironments. Here, an array of self-assembling peptides is designed, and peptide L5 is screened out based on its gel formation property and bioavailability. L5 exerted a pH-switchable antimicrobial effect (pH 5.5) and formed biocompatible hydrogels at neutral pH (pH 7.4). The LysSYL-loaded L5 can assemble L5@LysSYL hydrogels, increase thermal stability, and exhibit the slow-release effect of LysSYL. Effective elimination of S. aureus is achieved by L5@LysSYL through bacterial membrane disruption and cell separation inhibition. Moreover, L5@LysSYL hydrogels exhibit great potential in promoting wound healing in a mouse wound model infected by MRSA. Furthermore, L5@LysSYL hydrogels are safe and can decrease the cytokine levels and increase the number of key factors for vessel formation, which contribute to wound healing. Overall, the self-assembling L5@LysSYL can effectively clean MRSA and promote wound healing, which suggests its potential as a pH-sensitive wound dressing for the management of wound infections.

Metal-phenolic nanoparticles enhance low temperature photothermal therapy for bacterial biofilm in superficial infections.

Bacterial infections, especially induced by multidrug-resistant pathogens, have become a significant global health concern. In the infected tissues, biofilms not only serve as a source of nutrients but also act as protective barriers that impede antibiotic penetration. Herein, we developed tea polyphenols epigallocatechin gallate (EGCG) Au nanoparticles (E-Au NPs) through direct one-step self-assembly methods by EGCG chelating with Au ions to eradicate antibiotic-resistant bacteria methicillin-resistant Staphylococcus aureus (MRSA) and prevent the formation of biofilm under near-infrared (NIR) irradiation. The outstanding antibacterial effect involved in mild photothermal therapy, reactive oxygen species production, pathogenicity-related genes regulation, and quinoprotein formation that were specific to the polyphenol-based NPs. The excellent antibacterial and anti-inflammatory therapeutic efficacy of E-Au NPs was validated and topically applied in murine MRSA-infected skin wounds and keratitis model in vivo to kill bacteria, reduce the inflammation response and promote wound healing. Furthermore, the ophthalmic and systemic biosafety profiles were thoroughly evaluated while no significant side effects were revealed achieving a balance between high-efficiency antibacterial properties and biocompatibility. This study provides an effective therapeutic agent of metal-phenolic materials for superficial tissue infection with favorable prognosis and potential in clinical translation.

Research on the TSPAN6 regulating the secretion of ADSCs-Exos through syntenin-1 and promoting wound healing.

Exosomes (Exos) from adipose-derived stem cells (ADSCs) have a high inclusion content and low immunogenicity, which helps to control inflammation and accelerate the healing of wounds. Unfortunately, the yield of exosomes is poor, which raises the expense and lengthens the treatment period in addition to impairing exosomes' therapeutic impact. Thus, one of the key problems that needs to be resolved in the current exosome study is increasing the exosome yield. Tetraspanin-6 (TSPAN6) overexpression and knockdown models of ADSCs were constructed to determine the number of exosomes secreted by each group of cells as well as the number of multivesicular bodies (MVBs) and intraluminal vesicles (ILVs) within the cells. Subsequently, the binding region of the interaction between TSPAN6 and syntenin-1 was identified using the yeast two-hybrid assay, and the interaction itself was identified by immunoprecipitation. Finally, cellular and animal studies were conducted to investigate the role of each class of exosomes. When compared to the control group, the number of intracellular MVBs and ILVs was significantly larger, and the number of ADSCsTSPAN6+-Exos was more than three times higher. However, TSPAN6's ability to stimulate exosome secretion was reduced as a result of syntenin-1 knockdown. Additional yeast two-hybrid assay demonstrated that the critical structures for their interaction were the N-terminal, Postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ1), and PDZ2 domains of syntenin-1, and the C-terminal of TSPAN6. In animal trials, the wound healing rate was best in the ADSCsTSPAN6+-Exos group, while cellular experiments demonstrated that ADSCsTSPAN6+-Exos better enhanced the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs). TSPAN6 stimulates exosome secretion and formation, as well as the creation of MVBs and ILVs in ADSCs. Syntenin-1 is essential for TSPAN6's stimulation of ADSCs-Exos secretion. Furthermore, ADSCsTSPAN6+-Exos has a greater ability to support wound healing, angiogenesis, and the proliferation and migration of a variety of cells.

Mycosynthesis of silver nanoparticles from endophytic Aspergillus parasiticus and their antibacterial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant and biofilm-forming pathogenic bacteria with severe morbidity and mortality. MRSA showed resistance against currently available antibiotics. Thus, there is an urgent need to develop novel effective treatments with minimal side effects to eliminate MRSA.AimIn this study, we aimed to mycosynthesize silver nanoparticles (AgNPs) using the endophytic fungus Aspergillus parasiticus isolated from leaves of Reseda Arabica and to examine their antibacterial activity against MRSA.ResultsScreening of fungal secondary metabolites using gas chromatography–mass spectroscopy (GC–MS) analysis revealed the presence of high content of bioactive compounds with antibacterial activities. AP-AgNPs were mycosynthesized for the first time using ethyl acetate extract of A. parasiticus and characterized by imaging (transmission electron microscopy (TEM), UV–Vis spectroscopy, zeta potential, X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR)). The agar well diffusion method revealed the antibacterial activity of AP-AgNPs against MRSA with 25 μg/mL of minimum inhibitory concentration (MIC). AP-AgNPs were shown to exert antibacterial action via a bactericidal mechanism based on flow cytometry, scanning electron microscopy, and transmission electron microscopy assessment. Our data demonstrated the effective interaction of AP-AgNPs with the bacterial cell membrane, which resulted in cell membrane damage and disruption of cell surface structure. Furthermore, AP-AgNPs successfully prevented the development of MRSA biofilms by disturbing cell adhesion and destructing mature biofilm reaching over 80% clearance rate. Interestingly, topical application of AP-AgNPs to superficial skin infection induced by MRSA in mice effectively promoted wound healing and suppressed bacterial burden.ConclusionOur results provide a novel green nanoparticle drug design with effective therapeutic potential against MRSA-induced skin infection.

Gallic acid functionalized silk fibroin/gelatin composite wound dressing for enhanced wound healing

As the incidence of chronic wounds increases, the requirements for wound dressings are rising. The specific aim of this study is to propose a novel gallic acid (GA) functionalized silk fibroin (SF) and gelatin (Gel) composite wound dressing in which GA is used as an antibacterial and wound healing substance. Via electrospinning, SF, Gel, and GA mixed solutions could be conveniently fabricated into a composite nanofiber mat (SF-Gel-GA), consisting of uniform fibers with an average diameter around 134.57 ± 84 nm. The internal mesh structure of SF-Gel-GA provides sufficient drug loading capacity, proper moisture permeability, and proper degradation rate. SF-Gel-GA presents excellent biocompatibility. NIH-3T3 fibroblast cells could adhere and spread stably on the SF-Gel-GA surface with slightly promoted proliferation. In the presence of SF-Gel-GA, the growth of both Gram-positive and Gram-negative bacteria, includingStaphylococcus aureusandPseudomonas aeruginosa, is significantly inhibited in both plate and suspension cultures. A cutaneous excisional mouse wound model proves the efficient ability of SF-Gel-GA to promote wound healing. Compared with pure SF dressing and commercial Tegaderm Hydrocolloid3Mdressing, the wound closure rate with SF-Gel-GA treatment is significantly improved. The histological assessments further demonstrate SF-Gel-GA could facilitate collagen deposition, neovascularization, and epithelialization at wound sites to promote wound healing. In conclusion, a novel SF-Gel-GA composite wound dressing with efficient wound healing activities have been developed for chronic wound treatment with broad healing potential.

An ayurvedic approach to the management of Fissure-in-ano: A case Study

Background: In today's sedentary lifestyle, coupled with unhealthy dietary habits and stress, digestive disorders such as Fissure-in-ano have become prevalent. Fissure-in-ano is a longitudinal tear in the anal canal, most commonly occurring in the posterior midline, characterized by severe pain, burning sensation, and occasional bleeding. In Ayurveda, this condition aligns with Parikartika, often caused by improper administration of therapies like Basti (enema) or Virechana (purgative). Case Study: It explores the efficacy of per rectal Administration of Kaseesadi Taila for the management of Parikartika in a 35-year-old female patient presenting with anal pain, burning, and rectal bleeding post-defecation. Materials & Methods: It involved daily rectal Administration of Kaseesadi Taila (10ml) for 7 days. Results: It showed significant improvement by day 3, with complete relief of symptoms and healing of the fissure by day 7. The therapeutic benefits of Kaseesadi Taila are attributed to its Lekhana (scraping), Shodhana (cleansing), and Ropana (healing) properties, which promote wound healing, reduce inflammation, and facilitate easier bowel movements. Conclusion: Kaseesadi Taila is an effective, cost-efficient treatment for fissure-in-ano, providing significant symptom relief without the drawbacks of conventional surgical interventions.

Loureirin B Accelerates Diabetic Wound Healing by Promoting TGFβ/Smad-Dependent Macrophage M2 Polarization: A Concerted Analytical Approach Through Single-Cell RNA Sequencing and Experimental Verification.

Diabetic wound (DW) represent a significant clinical challenge and often fail to heal effectively. Loureirin B (LB), a flavonoid extracted from dragon's blood, has shown potential by influencing macrophage polarization and promoting wound healing. However, its mechanisms and efficacy in DW remain to be explored. This study employed single-cell RNA sequencing to analyze the classification of cells in diabetic foot ulcers and to identify the related mechanisms influenced by macrophages. Molecular docking was used to predict the interactions of LB with key proteins in the TGFβ/Smad signaling pathway. The effects of LB on macrophage polarization and wound healing were further validated through invitro and invivo experiments using a DW model. Single-cell analysis identified specific macrophage subtypes involved in the DW healing process and highlighted the role of the TGFβ/Smad pathway. Molecular docking suggested the potential action within the TGFβ/Smad pathway. Invitro studies showed that under high glucose conditions, LB promoted macrophage polarization from pro-inflammatory M1 to healing-promoting M2 and ECM production in fibroblasts by activating TGF-β/Smad signaling. Invivo, LB treatment enhanced wound healing rates in diabetic mice and promoted macrophage M2 polarization and fibroblast synthesis of ECM by activating TGF-β/Smad signaling. LB regulates macrophage M2 polarization and fibroblast synthesis of ECM by activating TGF-β/Smad signaling to promote DW healing. These findings suggest that LB could be a potential therapeutic agent for improving DW healing, emphasizing the need for further clinical studies to explore its efficacy and mechanisms in human subjects.

Pyroligneous extract, a biomaterial derived from pyrolytic palm kernel shell wood vinegar, as a novel diabetic wound healing aid: an animal study

Objective Wound in diabetes is difficult to heal since it possesses excessive inflammation. The aim of the study was to evaluate wound healing activity of chitosan-based hydrogel containing pyroligneous acid in diabetic animals. Significance Pyroligneous acid, a byproduct of biochar production from palm kernel shell biomass, contained oxygenated compounds which, with extracting enrichment, could promote wound healing. Methods Streptozotocin-induced diabetic male jcl: ICR mice were subjected to create wounds and treat with hydrogel containing pyroligneous extract at dose strengths of 0 (placebo), 100 and 150 µg/g-gel. Commercial gel (Intrasite®) was used as an active comparator. On 3-, 7-, 10- and 14-day post-wounding, wound contraction was rated and wound site tissues were collected. The specimens were H&E stained and microscopically examined to evaluate histological responses. The underline wound healing related cytokine and polypeptide expressions were determined using real-time PCR and western blot. Results It was found that the extract accelerated the healing process in a dose-dependent manner where at dose strength of 150 µg/g-gel was as effective as active comparator. It increased gene expression of the cytokine and related proteins in TGF-β/SMAD signaling pathway and may further activate diabetic induced TGF-β downregulation to restore up to the level that healthy skin tissues express. It also enhanced the expressions of Akt, FAK, RhoA and Rac-1 and evidently activated phosphorylation of Akt and FAK. Conclusion The study demonstrated the extract could be a novel biomaterial for healing of such a chronic inflammatory wound as the wound in diabetes.

Effects of Matricaria aurea extract in excisional wound healing on albino rats

The Asteraceae herbal plant Matricaria aurea (Loefl.) Sch.Bip is well known for its use in treating gastrointestinal, cardiac, pulmonary, rheumatologic and many other ailments; nevertheless, wound care has not yet received scientific validation. This study was done to evaluate the efficacy of M. aurea topical formulation on the rate of wound healing and contraction and the histopathological properties of the healing tissue in a rat model of an excisional wound. A total of 45 male rats with excisional wounds were enrolled in the study. The rats were divided into three groups, each with 15 male rats weighing approximately 200–250 g. The first group received treatment with M. aurea, the second group received fusidic acid cream and the third group received normal saline. The treatment was administered for 15 days while photographs were taken every other day, the diameters were measured and a histopathologic examination was conducted. There was a significant accelerated effect for wound healing, as evidenced by the inflammatory cells and diameters reducing to almost the same degree in the M. aurea and fusidic acid groups as compared to the control group (p<0.05). In vivo, the healing of wounds in albino Wister rats is demonstrated by the ethanolic extract of M. aurea. The findings, which show enhanced contraction, epithelization and tensile strength, significantly imply that wound healing promotion and acceleration can be achieved based on faster healing as compared to negative control and similar to standard control (fusidic acid) wounds.

Umbilical cord mesenchymal stem cells combined with autologous platelet-rich plasma for lower extremity venous ulcers: A case report and literature review.

Nonhealing ulcers are difficult to manage because they deviate from the normal wound healing process. Conventional therapy cannot achieve satisfactory therapeutic effects. To verify the effectiveness of combined treatment with human umbilical cord mesenchymal stem cells (hUMSCs) and platelet-rich plasma (PRP) for nonhealing ulcers, we studied a patient with left lower limb venous ulcer (LEVU) treated with combined injection therapy. We present the case of a LEVU patient who has not healed for a long period of time (up to 1 year). LEVU was diagnosed with clinical symptoms. The hUMSCs plus PRP were injected into the wound edge and base (1 µL of cells/cm2 of wound surface), 0.5 mL at each point, with a distance of approximately 1 to 3 cm between points. The injection point was determined according to the extent of wound involvement. Seven days after hUMSC + PRP application, the wound area decreased by nearly 50%. The ulcers had almost completely healed by day 62, and no serious treatment-related toxic side effects were observed. hUMSCs can improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. PRP has also been suggested to promote wound healing through the secretion of various nutritional factors. The combination of hUMSCs and PRP has a mutually reinforcing effect, which may achieve a 1 + 1 > 2 effect. Therefore, the combination of hUMSCs and PRP may be a safe and effective treatment option for LEVU.

MiR-155 promotes m6A modification of SOX2 mRNA through targeted regulation of HIF-1α and delays wound healing in diabetic foot ulcer in vitro models.

Diabetic foot ulcers (DFU) are one of the most destructive complications of diabetes mellitus. The aim of this study was to link miR-155 and SOX2 with DFU to explore the regulation of wound healing by DFU and its potential mechanism. Human keratinocytes (HaCaT) were induced with advanced glycation end products (AGEs) to construct DFU models in vitro. AGE-induced HaCaTcells were subjected to CCK-8 assays, flow cytometry, and wound healing assays to evaluate cell proliferation, apoptosis, and migration capacity, respectively. RT-qPCR and Western blotting were used to determine gene and protein expression levels, respectively. N6-methyladenosine (M6A) levels in total RNA were assessed using an M6A methylation quantification kit. Our results suggested that the inhibition of miR-155 promoted wound healing in an in vitro DFU model, while the knockdown of HIF-1α reversed this process, and that HIF-1α was a target protein of miR-155. In addition, knockdown of HIF-1α promoted the m6A level of SOX2 mRNA, inhibited the expression of SOX2, and inhibited the activation of the EGFR/MEK/ERK signaling pathway, thus inhibiting the proliferation and migration of HaCaTcells and promoting the apoptosis of HaCaTcells, while overexpression of SOX2 reversed this effect. We also found that METTL3 knockdown had the opposite effect of HIF-1α knockdown. Inhibition of miR-155 promoted the expression of HIF-1α and attenuated the m6A modification of SOX2 mRNA, thereby promoting the expression of SOX2 and activating the downstream EGFR/MEK/ERK signaling pathway to promote wound healing in an in vitro DFU model.

A functional dual responsive CMC/OHA/SA/TOB hydrogel as wound dressing to enhance wound healing.

Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague-Dawley (SD) rat was employed to investigate the hydrogel's wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel's proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Postbiotic Metabolite Derived from Lactiplantibacillus plantarum PD18 Maintains the Integrity of Cell Barriers and Affects Biomarkers Associated with Periodontal Disease

Background/Objectives: Periodontal disease is caused by oral infections, biofilms, persistent inflammation, and degeneration of cell barrier integrity, allowing pathogens to invade host cells. Probiotics have been extensively studied for the treatment of periodontal disease. However, research on the involvement of beneficial substances produced by probiotics, called “postbiotics,” in periodontal diseases remains in its early stages. The present study aimed to evaluate the effect of a postbiotic metabolite (PM) from Lactiplantibacillus plantarum PD18 on immunomodulation and maintenance of cell barrier integrity related to periodontal disease. Method: The main substance in PM PD18 was analyzed by GC-MS. The cytotoxic effect of PM PD18 was performed using the MTT assay, wound healing through the scratch assay, cell permeability through TEER value, modulation of inflammatory cytokines through ELISA, and gene expression of inflammatory cytokines and tight junction protein was determined using qRT-PCR. Results: The main substance found in PM PD18 is 2,3,5,6-tetramethylpyrazine. PM PD18 did not exhibit cytotoxic effects on RAW 264.7 cells but promoted wound healing and had an antiadhesion effect on Porphyromonas gingivalis concerning SF-TY cells. This postbiotic could maintain cell barrier integrity by balancing transepithelial electrical resistance (TEER) and alkaline phosphatase (ALP) activity. In addition, the gene and protein expression levels of zonula occludens-1 (ZO-1) increased. PM PD18 was found to have immunomodulatory properties, as demonstrated by regulated anti- and pro-inflammatory cytokines. Interleukin-10 (IL-10) increased, while IL-6 and IL-8 were reduced. Conclusions: This study demonstrated that PM PD18 is efficient as a natural treatment for maintaining cell barrier integrity and balancing inflammatory responses associated with periodontal disease.