Efficient Wound Healing Research Articles

Bio-friendly oleic acid-based ufasomal topical gel of rosuvastatin for diabetic wound healing: In-vitro, ex-Vivo, and in-Vivo evaluation

This study aimed to develop bio-friendly and biodegradable oleic acid-based ufasomes coated with chitosan for topical delivery of rosuvastatin for diabetic wound healing. Rosuvastatin was chosen as a suitable candidate due to its wound healing properties. Thin film hydration technique was implemented for the preparation of ufasomes at various concentrations of oleic acid. The most promising formulation (UF 5) was coated with chitosan. The effect of oleic acid and chitosan concentrations on vesicle Size, zeta-potential, polydispersity index, entrapment efficiency, and in-vitro drug release study was assessed. Optimum chitosan-coated ufasomal dispersion (CUF 3) was subjected to further characterizations, such as FT-IR, TEM, in-vitro release, broth microdilution susceptibility test, the effect of storage, ex-vivo skin permeability study, and wound healing efficiency in rats. Finally, CUF 3 was incorporated into chitosan gel base and examined for wound healing efficiency in rats. Uncoated ufasomal dispersion (UF 5) possessed the smallest vesicle Size (149.6 nm), the highest entrapment efficiency (79.48 %), an optimum zeta-potential (−35.78 mv), with polydispersity index of 0.18. FT-IR of coated ufasomes (CUF 3) reflected the effective coating of chitosan on the surface of ufasomes which coincided with the TEM image. Similar release profiles of UF 5 and CUF 3 were observed after 4 h of dissolution due to chitosan coating surrounding ufasomes. The cumulative percent of drug permeated across rat skin after 24 h for CUF 3 dispersion, and CUF 3 in chitosan gel were 11.21 % and 10.48 %, respectively, in comparison to 2.97 % in case of control gel. This was confirmed from the results of flux and permeability coefficient. A maximum skin retention and a controlled release effect with a reduced risk of systemic absorption of rosuvastatin were attained by CUF 3 in chitosan gel. Rosuvastatin encapsulated in ufasomal vesicles augmented the antimicrobial activity against Gram-negative and Gram-positive bacteria. A remarkable wound healing of CUF 3 in chitosan gel was confirmed by morphological and histopathological studies. Oleic acid-based ufasomes coated with chitosan could be a promising bio-friendly carrier for rosuvastatin to obtain a triple effect formulation for diabetic wound healing.

Ambient Synthesis of Porphyrin-Based Fe-Covalent Organic Frameworks for Efficient Infected Skin Wound Healing.

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.

Multifunctional Drug- and AuNRs-Loaded ROS-Responsive Selenium-Containing Polyurethane Nanofibers for Smart Wound Healing.

Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.

YAP/TAZ Drive Agrin–Matrix Metalloproteinase 12–Mediated Diabetic Skin Wound Healing

Macroscopic loss of extracellular matrix (ECM) can lead to chronic defects in skin wound healing, but supplementation of ECM holds promise for facilitating wound closure, particularly in diabetic wound healing. We recently showed that the ECM proteoglycan agrin accelerates cutaneous wound healing by improving mechanoperception of migrating keratinocytes and allowing them to respond to mechanical stresses via matrix metalloproteinase-12 (MMP12). RNA-sequencing analysis revealed that in addition to a disorganized ECM, agrin-depleted skin cells have impaired YAP/TAZ transcriptional outcomes, leading us to hypothesize that YAP/TAZ, as central mechanosensors, drive the functionality of agrin-MMP12 signaling during cutaneous wound repair. Herein, we demonstrate that agrin activates YAP/TAZ during migration of keratinocytes post-wounding in vitro and in vivo. Mechanistically, YAP/TAZ sustain agrin and MMP12 protein expression during migration post-wounding through positive feedback. YAP/TAZ silencing abolishes agrin-MMP12 mediated force-recognition and geometrical constraints. Importantly, soluble agrin (sAgrin) therapy accelerates wound closure in diabetic mouse models by engaging MMP12-YAP. Because patients with diabetic foot ulcers and impaired wound healing have reduced expression of agrin-MMP12 that correlates with YAP/TAZ inactivation, we propose that timely activation of YAP/TAZ by sAgrin therapy can accentuate mechanobiological microenvironments for efficient wound healing, under normal and diabetic conditions.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

Advanced Multifunctional Hydrogels for Enhanced Wound Healing through Ultra-Fast Selenol-SNAr Chemistry.

Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on-demand degradable hydrogels with multilevel responsiveness. By employing selenol-dichlorotetrazine nucleophilic aromatic substitution (SNAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds-diselenide, aryl selenide, and dearomatized selenide-in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self-healing and on-demand degradation properties. Furthermore, the resulting material demonstrated light-triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se-Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se-Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se-Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.

Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway.

Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing. This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line. We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 μg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.

Temperature/pH Co-responsive CS/NIPAM-Based hydrogel with controlled release of Ga3+ for improved infected wound healing

The treatment of infected wounds remains challenging due to the lack of an ideal wound therapy material. Herein, We present a multifunctional hydrogel dressing material containing gallium ion (Ga3+) based on a physicochemical dual network via in situ free radical polymerization. The presence of Ga3+ not only improves the elasticity and thermal stability of the hydrogel dressing through chelation but also enables smart response release. Fabricated hydrogel dressing possesses large-area plasticity, adequate elasticity, skin adhesion, and peelability. Furthermore, the dressing is responsive to temperature and pH, which can intelligently release Ga3+ according to pH and temperature variations in different healing stages of the wound microenvironment. In vivo infected wound experiments validated the significant wound healing efficiency (healing ratio is 95.75 % in 7 days, 14 % higher than the control group). These results show the promising potential of the developed multifunctional materials for accelerating the healing of infected wounds.

Exploring Skin Wound Healing Models and the Impact of Natural Lipids on the Healing Process.

Cutaneous wound healing is a complex biological process involving a series of well-coordinated events aimed at restoring skin integrity and function. Various experimental models have been developed to study the mechanisms underlying skin wound repair and to evaluate potential therapeutic interventions. This review explores the diverse array of skin wound healing models utilized in research, ranging from rodent excisional wounds to advanced tissue engineering constructs and microfluidic platforms. More importantly, the influence of lipids on the wound healing process is examined, emphasizing their role in enhancing barrier function restoration, modulating inflammation, promoting cell proliferation, and promoting remodeling. Lipids, such as phospholipids, sphingolipids, and ceramides, play crucial roles in membrane structure, cell signaling, and tissue repair. Understanding the interplay between lipids and the wound microenvironment provides valuable insights into the development of novel therapeutic strategies for promoting efficient wound healing and tissue regeneration. This review highlights the significance of investigating skin wound healing models and elucidating the intricate involvement of lipids in the healing process, offering potential avenues for improving clinical outcomes in wound management.

Chitosan/PVA Films and Silver Nanoparticle Impregnated Nanofibrous Dressings for Evaluation of their Wound Healing Efficacy in Wistar Albino Rat Model

The exoskeleton of marine shrimp contains a natural, biocompatible polymer chitin, which is dumped as a waste. The study proposes the sustainable single-pot-extraction of chitosan from the waste and its use in the fabrication of wound-dressings, and thus leverage its piezoelectric, antioxidant, hypoglycaemic and medicinal properties in wound-healing. The Fourier transform infrared spectrum revealed that marine chitosan contains functional groups with N-O, O-H, and CO stretching. Scanning electron micrographs demonstrated the spherical and mesoporous structures of the extracted chitosan. X-ray diffraction analysis showed a semi-crystalline phase of chitosan particles with a mean size of 28.9 nm. The film prepared with marine shrimp chitosanpolyvinyl alcohol (PVA) composite, and used as a wound dressing exhibited significant wound healing properties with a regeneration efficiency of 78% in 8 days in Wistar albino rats. The wound healing efficiency was enhanced by the addition of cost effective, non-toxic/environmentally friendly silver nanoparticles (AgNPs) synthesized from Rumex acetosa (sorrel) plant extracts and electrospinning of the nanofibrous composites of chitosan/PVA/AgNPs with high antibacterial, antioxidant and wound healing capacity of 96% in 8 days. Thus, the current study supports the use of a natural piezoelectric chitosan polymer as a wound dressing material, either in film or nanofiber, for normal as well as diabetic wounds.

Recombinant human collagen I/carboxymethyl chitosan hydrogel loaded with long-term released hUCMSCs derived exosomes promotes skin wound repair

BackgroundStem cell exosomes are beneficial in accelerating wound repair. However, the therapeutic function is limited due to its rapid clearance in vivo. To improve the functionality of exosomes in cutaneous wound healing, a novel hydrogel was designed and fabricated by recombinant human collagen I and carboxymethyl chitosan loaded with exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs), named as the rhCol I/CMC-Exos hydrogel. MethodsExosomes were extracted from hUCMSCs and were characterizated by TEM (Transmission Electron Microscopy), and biomarker detection. The rhCol I hydrogel, rhCol I/carboxymethyl chitosan (rhCol I/CMC) hydrogel and the rhCol I/CMC-Exos hydrogel composites were cross-linked by genipin. These materials were assessed and compared for their physical characteristics, including cross-sectional morphology, porosity, pore distribution, and hydrophilicity. Cell biocompatibility on biomaterials was investigated using scanning electron microscopy and CFDA staining, as well as assessed in vivo through histological examination of major organs in mice. Effects of the hydrogel composite on wound healing were further evaluated by using the full-thickness skin defect mice model. ResultsSuccessful extraction of hUCMSCs-derived exosomes was confirmed by TEM，Western Blotting and flow cytometry. The synthesized rhCol I/CMC-Exos hydrogel composite exhibited cytocompatibility and promoted cell growth in vitro. The rhCol I/CMC-Exos hydrogel showed sustained release of exosomes. In the mice full skin-defects model, the rhCol I/CMC-Exos-treated group showed superior wound healing efficiency, with 15 % faster wound closure compared to controls. Histological examinations revealed thicker dermis formation and more balanced collagen deposition in wounds treated with rhCol I/CMC-Exos hydrogel. Mechanistically, the application of rhCol I/CMC-Exos hydrogel increased fibroblasts proliferation, alleviated inflammation responses as well as promoted angiogenesis, thereby was beneficial in promoting skin wound healing and regeneration. ConclusionOur study, for the first time, introduced recombinant human Collagen I in fabricating a novel hydrogel loaded with hUCMSCs-derived exosomes, which effectively promoted skin wound closure and regeneration, demonstrating a great potential in severe skin wound healing treatment.

Herbal Products-Powered Thermosensitive Hydrogel with Phototherapy and Microenvironment Reconstruction for Accelerating Multidrug-Resistant Bacteria-Infected Wound Healing.

Wound healing and infection remain significant challenges due to the ineffectiveness against multidrug-resistant (MDR) bacteria and the complex oxidative wound microenvironments. To address these issues, thymoquinone-reinforced injectable and thermosensitive TQ@PEG-PAF-Cur hydrogels with dual functions of microenvironment reshaping and photodynamic therapy are developed. The hydrogel comprises natural compound thymoquinone (TQ) and poly (ethylene glycol)-block-poly (alanine-co-phenyl alanine) copolymers (PEG-PAF) conjugated with natural photosensitizer curcumin (Cur). The incorporation of TQ and Cur reduces the sol-to-gel transition temperature of TQ@PEG-PAF-Cur to 30°C, compared to PEG-PAF hydrogel (37°C), due to the formation of strong hydrogen bonding, matching the wound microenvironment temperature. Under blue light excitation, TQ@PEG-PAF-Cur generates significant amounts of reactive oxygen species such as H2O2, 1O2, and ·OH, exhibiting rapid and efficient bactericidal capacities against methicillin-resistant Staphylococcus aureus and broad spectrum β-lactamases Escherichia coli via photodynamic therapy (PDT). Additionally, Cur effectively inhibits the expressions of proinflammatory cytokines in skin tissue-forming cells. As a result, the composite hydrogel can rapidly transform into a gel to cover the wound, reshape the wound microenvironment, and accelerate wound healing in vivo. This collaborative antibacterial strategy provides valuable insights to guide the development of multifunctional materials for efficient wound healing.

Development of Poly(vinyl alcohol)-Chitosan Composite Nanofibers for Dual Drug Therapy of Wounds.

Current trends in localized drug delivery are emphasizing the development of dual drug-loaded electrospun nanofibers (NFs) for an improved therapeutic effect on wounds, especially infected skin wounds. The objective of this study was to formulate a new healing therapy for an infected skin wound. To achieve this goal, this study involved the development and characterization of poly(vinyl alcohol) (PVA)/chitosan nanofibers loaded with ciprofloxacin and rutin hydrate. Polymers and drugs were used in different ratios. Nanofiber morphology was studied by scanning electron microscopy, thermal stability by thermogravimetric analysis, structural determination by the X-ray diffraction method, and integrity by Fourier transform infrared spectroscopy. Dissolution studies were performed to check the drug release behavior of the formulations. Antibacterial studies were performed against Staphylococcus aureus and Pseudomonas aeruginosa. The wound healing efficiency of dual drug-loaded nanofibers was measured by a full-thickness excisional wound model of rabbits. The fabricated nanofibers were smooth in morphology. According to FTIR findings, the drugs remained intact in the nanofibers. The results of swelling ratio and porosity revealed that the pore size was increased as the amount of chitosan was increased up to 30% but a further increase in chitosan concentration reduced the swelling ratio and porosity. Drug release studies of nanofibers depicted an initial burst effect and afterward controlled drug release behavior. Drug-loaded nanofibers showed better activity against S. aureus than P. aeruginosa. The antibacterial efficacy of rutin hydrate with ciprofloxacin was improved compared to that of the formulation having rutin hydrate only, likely due to the additive effect in activity. Based on wound healing studies, nanofibrous membranes acted as a promising wound dressing material as compared to the commercial wound healing formulation. Drug-loaded polymeric nanofibers were successfully fabricated by using an electrospinning method. These nanofibers showed an efficient ability to deliver drugs and treat infected wounds.

The effect of traditional Chinese medicine soaking method on the healing of diabetic foot ulcers: A meta-analysis.

Foot infections, sores or deep tissue damage from diabetes can be a serious psychological and physical injury. This paper aims at making meta-analyses on the therapeutic effects of traditional Chinese medicine (TCM) on diabetic foot ulcers. The Chinese National Knowledge Infrastructure, VIP Database, Wanfang Database and so on, has conducted a randomized controlled trial to evaluate the clinical effect of TCM soaking method for diabetes patients with diabetes. Literature has been determined to be included by computer search and by hand rough checks. The search period was from the creation of the database to October 2023. Review Manager 5.3 was used to analyse the meta data and evaluate it systematically. Altogether, 479 research was conducted in China's data base and 20 of them were eventually collected for the final statistical analysis. In all, 1361 patients were enrolled in the trials. The results indicated that TCM immersion in diabetic foot resulted in significantly improved obvious wound healing (OR, 3.2; 95% CI, 2.5, 4.09, p < 0.0001); results showed that TCM immersion therapy significantly increased the efficiency of effective wound healing (OR, 4.55; 95% CI, 3.25, 6.37, p < 0.001). Statistical significance was found. Using Egger's approach to detect publishing bias suggests that there is no risk of publishing bias in terms of marked wound healing and effective healing. Traditional Chinese drug immersion can increase obviously the recovery ratio and the effective recovery ratio of diabetic foot.

Cohering Plasma into Adhesive Gel by Natural Biopolymer-Nanoparticle Hybrid Powder for Efficient Hemostasis and Wound Healing.

Hemostatic powder is commonly used in emergency bleeding control due to its suitability for irregularly shaped wounds, ease of use, and stable storage. However, traditional powder often has limited tissue adhesion and weak thrombus support, which makes it vulnerable to displacement by blood flow. Herein, we have developed a tricomponent hemostatic powder (MQS) composed of mesoporous bioactive glass nanoparticle (MBG), positively charged quaternized chitosan (QCS), and negatively charged catechol-modified alginate (SADA). Upon application to the wound, MBG with its high specific surface area quickly absorbs plasma, concentrating the blood coagulation factor. Simultaneously, the water-soluble QCS and SADA interact with each other and form a net, which can be further cross-linked by MBG. This network efficiently binds and entraps clustered blood coagulation factors, ultimately resulting in the formation of a durable and robust thrombus. Furthermore, the formed net adheres to the injury site, offering protection against thrombus disruption caused by the bloodstream. Benefiting from the synergistic effect of these three components, MQS demonstrates superior hemostatic performance compared to commercial hemostatic powders like Celox in both arterial injuries and noncompressible liver puncture wounds. Furthermore, MQS can effectively accelerate wound healing. In addition, MQS exhibits excellent antibacterial activity, cytocompatibility, and hemocompatibility. These advantages of MQS, including strong blood clotting, wet tissue adherence, antibacterial activity, wound healing ability, biosafety, ease of use, and stable storage, make it a promising hemostatic agent for emergency situations.

Multifunctional chitosan-based hydrogels: characterization and evaluation of biocompatibility and biodegradability in vitro

Creation of novel remedies efficient in supporting wound healing remains an actual task in pharmacology. Hydrogels showed high efficiency in wound healing and tissue regeneration due to viscosity, elasticity and fluidity that provide them with functional characteristics similar to that in extracellular matrix. The aim of the study was to create chitosan-based hydrogels functionalized with different components (chondroitin-6-sulfate, hyaluronic acid, N-stearoylethanolamine) and to estimate their biocompatibility and biodegradabili­ty in vitro. For the first time, a lipid substance N-stearoylethanolamine (NSE) known as suppressor of pro-inflammatory cytokines expression was used as hydrogel component (1.95 mg/g). FTIR analysis confirmed the complexation of chitosan molecule with hyaluronate, chondroitin-6-sulfate, NSE. MTT-test and Trypan blue exclusion test were used to study hydrogels cytotoxicity towards human cells of different tissue origin. Biodegradability of hydrogels was evaluated using direct hydrogel contact with cells and cell-independent degradation. It was shown that chondroitin-6-sulfate (&lt;2 mg/ml), hyaluronic acid (&lt;2 mg/ml) and NSE (26 µg/ml) did not demonstrate significant toxic effects towards pseudonormal human cells of the MCF10A, HaCat, HEK293 lines and mouse cells of the Balb/3T3 line. The studied hydrogels were stable in saline solution, while in a complete culture medium containing 10% fetal bovine blood serum they underwent degradation in &gt;24 h. The identified biodegradability of the chitosan-based hydrogels is important for the release of noncovalently immobilized NSE into biological medium. Further studies on laboratory animals with experimental wounds are expected to explore the potential of created hydrogels as anti-inflammatory and wound-healing agents. Keywords: biodegradability, chitosan hydrogels, chondroitin-6-sulfate, FTIR analysis, human pseudonormal cells, hyaluronic acid, N-stearoylethanolamine, toxicity

Multifunctional gelatin nanoparticle stabilized-Pickering emulsion hydrogel based on dextran and amikacin with controlled drug release and enhanced antibacterial capability for promoting infected wound healing

Plant essential oils possess broad-spectral antimicrobial property, but the applications are impeded by their insolubility in water, extreme volatility, and strong irritation. Nanoparticle-stabilized emulsion (Pickering emulsion) gels are colloidal systems with ability to accommodate two immiscible phases in one system. The thick adsorption nanoparticle layers and the cross-linked networks in continuous phase could provide protective barriers for antibacterial oil and achieve on-demand controlled release. An emulsion hydrogel templated from gelatin nanoparticle-stabilized emulsion is one-pot constructed by conducting a tunable cross-linking process between oxidized dextran (Odex) and amikacin in the continuous phase and concomitantly trapping tea tree essential oil (TO) droplets in the three-dimensional network. The resulted emulsion hydrogel presents tunable gelation time, adequate mechanical strength, fascinating injectability, and self-healing capability. It is pH-responsiveness and presents controlled release of amikacin and TO, exhibiting a long-term bacteriostasis of 144 h. The emulsion hydrogel facilitates the outstanding wound healing efficiency in 14 days (95.2 ± 0.8 % of wound closure), accompanied with enhanced collagen deposition and angiogenic activities. The incorporation of TO into emulsion hydrogel system reduced its irritation and improved its biosafety, showing potential application in bacteria inhibition even as implants in vivo.

Versatile Bioactive Glass/Zeolitic Imidazolate Framework-8-Based Skin Scaffolds toward High-Performance Wound Healing.

Designing a novel biomaterial for wound healing is based on biocompatibility and excellent mechanical strength. In this study, bioactive glass (BG) and zeolitic imidazolate framework-8 (ZIF-8) have been incorporated into poly(ε-caprolactone)/poly(vinyl alcohol) (PCL/PVA) composite skin scaffolds via microfluidic electrospinning. Interestingly, the addition of ZIF-8 further strengthens the BG stability and demonstrates better antibacterial effects. Utilizing the slow release of Zn, Ca, and Si ions, it also significantly promotes growth factor expression and skin regeneration. In addition, it is further demonstrated by in vitro and in vivo studies that the prepared composite skin scaffolds possess excellent biocompatibility, antibacterial capabilities, and mechanical properties. The prepared BG/ZIF-8-loaded scaffold possesses high tensile strength (26 MPa) and excellent antibacterial properties (achieves 89.64 and 78.8% inhibition of E. coli and S. aureus, respectively), and cell viability increased by 51.2%. More importantly, the wound shrinkage of the BG/ZIF-8-loaded scaffold is better than that of an unloaded scaffold, and the shrinkage rates of PCL/PVA@BG/ZIF-8(1 wt %) group is 95% with 2.2 mm granulation growth thickness within 12 days. Thus, the composite skin scaffold loaded with BG/ZIF-8 prepared by microfluidic electrospinning provides a new perspective for accelerating wound healing and is a potential novel therapeutic strategy for efficient wound healing.

Robust and Wet Adhesive Self-Gelling Powders for Rapid Hemostasis and Efficient Wound Healing.

Healing traumatic wounds is arduous, leaving miscellaneous demands for ideal wound dressings, such as rapid hemostasis, superior wet tissue adhesion, strong mechanical properties, and excellent antibacterial activity. Herein, we report a self-gelling, wet adhesive, stretchable (polyethylenimine/poly(dimethylammonium chloride)/(poly(acrylic acid)/poly(sodium styrenesulfonate)/alkylated chitosan)) ((PEI/PDDA)/(PAA/PSS)/ACS) powder as a new option. The self-gel utilizes noncovalent interactions among in situ formed PDDA/PSS nanoparticles and PEI/PAA polymetric matrices to earn sensational mechanical properties and tensile strength while incorporating ACS to obtain fast hemostasis and therapeutic capacities. The powder can form a hydrogel patch in situ within 3 s upon liquid absorption, capable of resisting pressure higher than twice the blood pressure. Deposition of the self-gelling powders on various wounds, such as rat liver and femoral artery wounds, can stop bleeding in 10 s and lessen the amount of bleeding 6-fold plus in corresponding models. Furthermore, the self-gelling powders can significantly advance the chronic wound healing process by displaying a high wound healing rate and a low inflammatory response and promoting the formation of new blood vessels and tissue regeneration. The satisfactory mechanical properties, strong wet adhesion, sufficient antibacterial properties, ease of usage, adaptability to complex wounds, rapid hemostasis, and superior therapeutic capacities of (PEI/PDDA)/(PAA/PSS)/ACS self-gelling powders render them as a profound wound dressing biomaterial.

Multifunctional Wound Curation Dressing Material FemuFrost─An Antioxidant-Loaded Nanoemulsion Frosted Patch of Poly(vinyl alcohol) and Hyaluronic Acid.

The wound curation dressing material should own explicit elements to aggrandize wound cessation. The cryogel of poly(vinyl alcohol) (PVA) and hyaluronic acid (HA) is deemed to promote the angiogenesis, production of extracellular matrix components, granulation, and epithelialization. The research aims to tailor and evaluate the composite PVA/HA cryogel ingrained ferulic acid-loaded nanoemulsion patch labeled as PH-FemuFrost to improve the therapeutic properties and mechanical strength of the patches. The PH-FemuFrost exhibited a water uptake capacity of 268 ± 15.07%, porosity of 70.52 ± 7.4%, and 48.62 ± 2.2% in vitro degradation. The texture analysis revealed the improved mechanical properties of PH-FemuFrost in terms of burst strength and stiffness. The PH-FemuFrost exhibited in vitro antioxidant and antimicrobial activity against Staphylococcus aureus and Candida albicans species. The wound healing efficiency of PH-FemuFrost patches was significantly increased than blank PVA-HA patches. The groups treated with PH-FemuFrost exhibited a dense network of collagen type 1 in comparison to negative and PVA-HA groups. The normal skin and healed skin exhibited parallel arrangement of type I collagen fibers toward the skin. The levels of inflammatory mediators such as IL-6 (p value < 0.0001), IL-22 (p value 0.0098), and TNF-α levels (p value < 0.0001) of PH-FemuFrost is significantly reduced compared to the negative group.