Full-thickness Skin Defect Model Research Articles

Near-Infrared Stimuli-Responsive Hydrogel Promotes Cell Migration for Accelerated Diabetic Wound Healing.

Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring an increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for the healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin-based composite hydrogel, N-isopropylacrylamide and polydopamine nanoparticles were incorporated to endow the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel, and the drug release rate could be controlled by NIR laser irradiation. NIR-triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of the composite hydrogel. The release of loaded LIN could effectively promote cell migration by activating EMT and enhancing angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound closure rate as compared with the pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can serve as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.

Evaluation of the Composite Skin Patch Loaded with Bioactive Functional Factors Derived from Multicellular Spheres of EMSCs for Regeneration of Full-thickness Skin Defects in Rats.

Transplantation of stem cells/scaffold is an efficient approach for treating tissue injury including full-thickness skin defects. However, the application of stem cells is limited by preservation issues, ethical restriction, low viability, and immune rejection in vivo. The mesenchymal stem cell conditioned medium is abundant in bioactive functional factors, making it a viable alternative to living cells in regeneration medicine. Nasal mucosa-derived ecto-mesenchymal stem cells (EMSCs) of rats were identified and grown in suspension sphere-forming 3D culture. The EMSCs-conditioned medium (EMSCs-CM) was collected, lyophilized, and analyzed for its bioactive components. Next, fibrinogen and chitosan were further mixed and cross-linked with the lyophilized powder to obtain functional skin patches. Their capacity to gradually release bioactive substances and biocompatibility with epidermal cells were assessed in vitro. Finally, a full-thickness skin defect model was established to evaluate the therapeutic efficacy of the skin patch. The EMSCs-CM contains abundant bioactive proteins including VEGF, KGF, EGF, bFGF, SHH, IL-10, and fibronectin. The bioactive functional composite skin patch containing EMSCs-CM lyophilized powder showed the network-like microstructure could continuously release the bioactive proteins, and possessed ideal biocompatibility with rat epidermal cells in vitro. Transplantation of the composite skin patch could expedite the healing of the full-thickness skin defect by promoting endogenous epidermal stem cell proliferation and skin appendage regeneration in rats. In summary, the bioactive functional composite skin patch containing EMSCs-CM lyophilized powder can effectively accelerate skin repair, which has promising application prospects in the treatment of skin defects.

Construction and Performance Study of a Dual-Network Hydrogel Dressing Mimicking Skin Pore Drainage for Photothermal Exudate Removal and On-Demand Dissolution.

In recent years, negative pressure wound dressings have garnered widespread attentions. However, it is challenging to drain the accumulated fluid under negative pressures for hydrogel dressings. To address this issue, this study prepared a chemical/physical duel-network PEG-CMCS/AG/MXene hydrogel composed by chemical disulfide crosslinked network of four-arm polyethylene glycol/carboxymethyl chitosan (4-Arm-PEG-SH/CMCS), and the physical network of hydrogen bond of agar (AG). Under near-infrared light (NIR) irradiation, the PEG-CMCS/AG/MXene hydrogel undergoes photothermal heating due to integrate of MXene, which destructs the hydrogen bond network and allows the removal of exudate through a mechanism mimicking the sweat gland-like effect of skin pores. The photothermal heating effect also enables the antimicrobial activity to prevent wound infections. The excellent electrical conductivity of PEG-CMCS/AG/MXene can promote cell proliferation under the external electrical stimulation (ES) in vitro. The animal experiments of full-thickness skin defect model further demonstrate its ability to accelerate wound healing. The conversion between thioester and thiol achieved with L-cysteine methyl ester hydrochloride (L-CME) can provides the on-demand dissolution of the dressing in situ. This study holds promises to provide a novel solution to the issue of fluid accumulations under hydrogel dressings and offers new approaches to alleviating or avoiding the significant secondary injuries caused by frequent dressing changes.

Chitosan/rutin multifunctional hydrogel with tunable adhesion, anti-inflammatory and antibacterial properties for skin wound healing

Effective wound care remains a significant challenge due to the need for infection prevention, inflammation reduction, and minimal tissue damage during dressing changes. To tackle these issues, we have developed a multifunctional hydrogel (CHI/CPBA/RU), composed of chitosan (CHI) modified with 4-carboxyphenylboronic acid (CPBA) and the natural flavonoid, rutin (RU). This design endows the hydrogel with body temperature-responsive adhesion and low temperature-triggered detachment, thus enabling painless removal during dressing changes. The CHI/CPBA/RU hydrogels exhibit excellent biocompatibility, maintaining over 97 % viability of L929 cells. They also demonstrate potent intracellular free radical scavenging activity, with scavenging ratios ranging from 53 % to 70 %. Additionally, these hydrogels show anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6, and iNOS) and increasing anti-inflammatory markers (Arg1 and CD206) in RAW 264.7 macrophages. Notably, they possess robust antimicrobial properties, inhibiting over 99.9 % of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus growth. In vivo testing on a murine full-thickness skin defect model shows that the hydrogel significantly accelerates wound healing by reducing inflammation, increasing collagen deposition, and promoting angiogenesis, achieving 98 % healing by day 10 compared to 78 % in the control group. These attributes make the polysaccharide-based hydrogel a promising material for advanced wound care.

Polyphenol-mediated hyaluronic acid/tannic acid hydrogel with short gelation time and high adhesion strength for accelerating wound healing

Wound healing is a complex process involving a complicated interplay between numerous cell types and vascular systems. Hyaluronic acid (HA)-based hydrogel facilitates wound healing, and is involved in all processes. However, slow gelation speed and weak adhesion strength limit its ability to form a stable physical barrier quickly. Herein, we propose a HA-based composite hydrogel as the wound dressing based on oxidative coupling reaction. Tannic acid and dopamine-coated carbon particles (DCPs) containing abundant phenolic hydroxyl groups are incorporated into the HA-based hydrogel for increasing the number of crosslinking sites of oxidative coupling of the hydrogel and enhancing adhesion through the formation of covalent bonds and hydrogen bonds between hydrogel and wound sites. The composite hydrogel exhibits short gelation time (<6 s) and high adhesion strength (>8.1 kPa), which are superior to the references and commercial products of its kind. The in vitro experiments demonstrate that the hydrogel has low hemolytic reaction, negligible cytotoxicity, and the ability to promote fibroblast proliferation and migration. The in vivo full-thickness skin defect model experiments demonstrate that the hydrogel can accelerate wound healing under mild photothermal stimulation of DCPs by reducing inflammation, relieving tissue hypoxia, and promoting angiogenesis and epithelialization.

Superior hemostatic and wound-healing properties of tetrastigma polysaccharide

Hemostatic materials that allow fast and convenient hemostasis are urgently needed. However, obtaining an ideal hemostatic agent that exhibits biocompatibility, biodegradability, and hemostatic efficacy remains challenging. Recent studies demonstrate that morphological characteristics of hemostatic materials impact their efficacy. This study reports on the importance of morphological modification of traditional Chinese medicine plant polysaccharides. The hemostatic properties of Three-leaf Qing polysaccharides, optimized in particle (SYQ-P) and sponge (SYQ-S) forms, were investigated in vitro and in vivo. SYQ-S and SYQ-P exhibit excellent biodegradability and biocompatibility, thereby improving fibroblast cell proliferation. The hemostatic mechanism involves stable blood clot formation through intrinsic coagulation pathways. In a lethal mouse liver defect bleeding model, blood loss and clotting time were lower with polysaccharides use than with commercial hemostatic drugs. SYQ-S demonstrates instant water-triggered expansion and high absorption capacity, while the sponge-like morphological characteristics effectively improve blood component concentrations. With efficient hemostasis and excellent biocompatibility, SYQ-S dramatically accelerated wound healing in a full-thickness skin defect model in vivo. Thus, SYQ-S effectively promotes the formation of granulation tissue, collagen deposition, and angiogenesis, which ultimately accelerates wound healing. Our work highlights the design of natural Chinese medicine polysaccharides and presents a promising hemostatic agent for widespread clinical application.

Photodynamic-Controllable microneedle composite with Antibacterial, Antioxidant, and angiogenic effects to expedite infected diabetic wound healing

Effective treatment of infected diabetic wound (IDW) requires delivering therapeutic agents to both wound surface and deep layers, as well as improving the wound microenvironment through antibacterial actions, clearing excessive reactive oxygen species (ROS), and promoting vascular regeneration. Here, we present a novel inorganic nanosheet called MnO2/PDA@Cu, consisting of manganese dioxide (MnO2) with copper (Cu) ions loaded on its surface through in-situ polymerization, using polydopamine (PDA) as an intermediate. We then encapsulated the MnO2/PDA@Cu nanosheet into a methacrylated hyaluronic acid (HA) soluble microneedle patch, creating a photodynamic-controllable multifunctional MnO2/PDA@Cu-HA microneedle. We used this microneedle to treat IDWs in a rat full-thickness skin defect model. Results demonstrated that the MnO2/PDA@Cu-HA microneedle effectively delivered therapeutic agents to both wound surface and deep layers, where PDA's photodynamic therapy swiftly combated bacteria under 808 nm near-infrared irradiation. Simultaneously, MnO2 acted as a nanoenzyme, mitigating ROS levels and providing oxygen for wound healing. In addition, the photothermal effect of PDA further facilitated the release of Cu, promoting vascularization. The MnO2/PDA@Cu-HA microneedle significantly accelerated wound closure, re-epithelialization, and collagen deposition, enhancing IDW healing. In conclusion, our synthesized MnO2/PDA@Cu-HA microneedle represents a photodynamic-controllable multifunctional platform for IDW treatment, offering a promising approach for effective wound management.

Synergistic Antimicrobial Glycyrrhizic Acid-Based Functional Biosensing Composite for Sensitive Glucose Monitoring and Collaborative Wound Healing.

High glucose blood and bacterial infection remain major issues for the slow healing of diabetic wounds, so developing functional biosensing composite with excellent antibacterial and remarkable glucose response sensitivity is necessary and prospective. Herein, by in situ synthesis AgNPs on the surface of self-prepared PTIGA elastomers, PTIGA-AgNPs conductive composites are obtained with efficient synergistic antibacterial effect, excellent mechanical and self-healing properties. The strain of the composites can reach 1800%, and its self-healing efficiency exceeds 90% at 60°C within 8 h. Both elastomers and composites represent excellent biocompatibility and the antibacterial rate against E. coli and S. aureus exceeded 90%. Moreover, the biosensor assembled from the conductive composites exhibits excellent glucose response sensitivity and stability, with a sensitivity coefficient of 0.518mA mm-1 in the range of 0.2-3.6× 10-3 m glucose concentration, as well as a low detection limit of 0.08× 10-3 m. Furthermore, based on the remarkable antibacterial performance and bioactivity derived from GA, the composites reduce the expression of pro-inflammatory factors and promote the production of anti-inflammatory factors, and effectively promote the regeneration of skin and granulation tissue of wounds in a diabetic full-thickness skin defect model, demonstrating the enormous therapeutic potential in diabetic wound healing.

Fabrication of Quercetin-Functionalized Morpholine and Pyridine Motifs-Laden Silk Fibroin Nanofibers for Effective Wound Healing in Preclinical Study.

Choosing suitable wound dressings is crucial for effective wound healing. Spun scaffolds with bioactive molecule functionalization are gaining attention as a promising approach to expedite tissue repair and regeneration. Here, we present the synthesis of novel multifunctional quercetin with morpholine and pyridine functional motifs (QFM) embedded in silk fibroin (SF)-spun fibers (SF-QFM) for preclinical skin repair therapies. The verification of the novel QFM structural arrangement was characterized using ATR-FTIR, NMR, and ESI-MS spectroscopy analysis. Extensive characterization of the spun SF-QFM fibrous mats revealed their excellent antibacterial and antioxidant properties, biocompatibility, biodegradability, and remarkable mechanical and controlled drug release capabilities. SF-QFM mats were studied for drug release in pH 7.4 PBS over 72 h. The QFM-controlled release is mainly driven by diffusion and follows Fickian's law. Significant QFM release (40%) occurred within the first 6 h, with a total release of 79% at the end of 72 h, which is considered beneficial in effectively reducing bacterial load and helping expedite the healing process. Interestingly, the SF-QFM-spun mat demonstrated significantly improved NIH 3T3 cell proliferation and migration compared to the pure SF mat, as evidenced by the complete migration of NIH 3T3 cells within 24 h in the scratch assay. Furthermore, the in vivo outcome of SF-QFM was demonstrated by the regeneration of fresh fibroblasts and the realignment of collagen fibers deposition at 9 days post-operation in a preclinical rat full-thickness skin defect model. Our findings collectively indicate that the SF-QFM electrospun nanofiber scaffolds hold significant capability as a cost-effective and efficient bioactive spun architecture for use in wound healing applications.

Dehydration-Toughing Dual-Solvent Gels with Viscoelastic Transition for Infectious Wound Treatment.

The modulus of traditional biomedical hydrogels increases exponentially meditated by dehydration-stiffing mechanism, which leads to the failure of interface matching between hydrogels and soft tissue wounds. It is found in the study that the dual-solvent gels exhibit dehydration-toughening mechanism with the slowly increasing modulus that are always match the soft tissue wounds. Therefore, dual-solvent glycerol hydrogels (GCFen-gly DGHs) are prepared with hydrophobically modified catechol chitosan (hmCSC) and gelatin based on the supramolecular interactions. GCFen-gly DGHs exhibit excellent water retention capacity with a total solvent content exceeding 80%, permanent skin-like modulus within a range of 0.45 to 4.13kPa, and stable photothermal antibacterial abilities against S, aureus, E. coli, as well as MRSA. Infectious full-thickness rat skin defect model and tissue section analysis indicate that GCFen-gly DGHs are able to accelerate infectious wound healing by alleviating the inflammatory response, promoting granulation tissue growth, re-epithelialization, collagen deposition, and vascular regeneration. As a result, GCFen-gly DGHs is expected to become the next-generation biological gel materials for infectious wound treatment.

A Spatiotemporal Controllable Biomimetic Skin for Accelerating Wound Repair.

Skin injury repair is a dynamic process involving a series of interactions over time and space. Linking human physiological processes with materials' changes poses a significant challenge. To match the wound healing process, a spatiotemporal controllable biomimetic skin is developed, which comprises a three-dimensional (3D) printed membrane as the epidermis, a cell-containing hydrogel as the dermis, and a cytokine-laden hydrogel as the hypodermis. In the initial stage of the biomimetic skin repair wound, the membrane frame aids wound closure through pre-tension, while cells proliferate within the hydrogel. Next, as the frame disintegrates over time, cells released from the hydrogel migrate along the residual membrane. Throughout the process, continuous cytokines release from the hypodermis hydrogel ensures comprehensive nourishment. The findings reveal that in the rat full-thickness skin defect model, the biomimetic skin demonstrated a wound closure rate eight times higher than the blank group, and double the collagen content, particularly in the early repair process. Consequently, it is reasonable to infer that this biomimetic skin holds promising potential to accelerate wound closure and repair. This biomimetic skin with mechanobiological effects and spatiotemporal regulation emerges as a promising option for tissue regeneration engineering.

Mussel-inspired electroactive, antibacterial and antioxidative composite membranes with incorporation of gold nanoparticles and antibacterial peptides for enhancing skin wound healing

Large skin wounds are one of the most important health problems in the world. Skin wound repair and tissue regeneration are complex processes involving many physiological signals, and effective wound healing remains an enormous clinical challenge. Therefore, there is an urgent need for a strategy to rapidly kill bacteria, promote cell proliferation and accelerate wound healing. At present, electrical stimulation (ES) is often used in the clinical treatment of skin wounds and can simulate the endogenous biological current of the body and accelerate the repair process of skin wounds. However, a single ES strategy has difficulty covering the entire wound area, which may lead to unsatisfactory therapeutic effects. To overcome this deficiency, it is essential to develop a collaborative treatment strategy that combines ES with other treatments. In this study, gold nanoparticles and antibacterial peptides (Os) were loaded on the surface of poly(lactic-co-glycolic acid) (PLGA) material through the reducibility and adhesion of polydopamine (PDA) and improved the electrical activity, anti-inflammatory, antibacterial and biocompatibility properties of the polymer material. At the same time, this composite membrane material (Os/Au-PDA@PLGA) combined with ES was used in wound therapy to improve the wound healing rate. The results show that the new wound repair material has good biocompatibility and can effectively promote cell proliferation and migration. Through the combined application of gold nanoparticles and antibacterial peptides Os, the polymer materials have more efficient bactericidal and antioxidant effects. The antibacterial experiment results showed that gold nanoparticles could further enhance the antibacterial activity of antibacterial peptides. Furthermore, the Os/Au-PDA@PLGA composite membrane has good hydrophilicity and electrical activity, which can provide a more favorable cell microenvironment for wound healing. In vivo studies using a full-thickness skin defect model in rats showed that the Os/Au-PDA@PLGA composite membrane had a better therapeutic effect than the pure PLGA material. More importantly, the combination of the Os/Au-PDA@PLGA composite with ES significantly accelerated the rate of vascularization and collagen deposition and promoted wound healing compared with non-ES controls. Therefore, the combination of the Au/Os-PDA@PLGA composite membrane with ES may provide a new strategy for the effective treatment of skin wounds.

Rapid innervation and physiological epidermal regeneration by bioengineered dermis implanted in mouse

Tissue-engineered skin substitutes are promising tools to cover large and deep skin defects. However, the lack of a synergic and fast regeneration of the vascular network, nerves, and skin appendages limits complete skin healing and impairs functional recovery. It has been highlighted that an ideal skin substitute should mimic the structure of the native tissue to enhance clinical effectiveness. Here, we produced a pre-vascularized dermis (PVD) comprised of fibroblasts embedded in their own extracellular matrix (ECM) and a capillary-like network. Upon implantation in a mouse full-thickness skin defect model, we observed a very early innervation of the graft in 2 weeks. In addition, mouse capillaries and complete epithelialization were detectable as early as 1 week after implantation and, skin appendages developed in 2 weeks. These anatomical features underlie the interaction with the skin nerves, thus providing a further cue for reinnervation guidance. Further, the graft displays mechanical properties, collagen density, and assembly features very similar to the host tissue. Taken together our data show that the pre-existing ECM components of the PVD, physiologically organized and assembled similarly to the native tissue, support a rapid regeneration of dermal tissue. Therefore, our results suggest a promising potential for PVD in skin regeneration.

Enzymatic functionalization of decellularized tilapia skin scaffolds with enhanced skin regeneration.

The decellularized tilapia skin (dTS) has gained significant attention as a promising material for tissue regeneration due to its ability to provide unique structural and functional components that support cell growth, adhesion, and proliferation. However, the clinical application of dTS is limited by its low mechanical strength and rapid biodegradability. Herein, we prepare a novel RGD (arginine-glycine-aspartic acid) functionalized dTS scaffold (dTS/RGD) by using transglutaminase (TGase) crosslinking. The developed dTS/RGD scaffold possesses excellent properties, including a medium porosity of ∼59.2%, a suitable degradation rate of approximately 80% over a period of two weeks, and appropriate mechanical strength with a maximum tensile stress of ∼46.36 MPa which is much higher than that of dTS (∼32.23 MPa). These properties make the dTS/RGD scaffold ideal for promoting cell adhesion and proliferation, thereby accelerating skin wound healing in a full-thickness skin defect model. Such an enzymatic cross-linking strategy provides a favorable microenvironment for wound healing and holds great potential for application in skin regeneration engineering.

Engineered nanovesicles from activated neutrophils with enriched bactericidal proteins have molecular debridement ability and promote infectious wound healing.

Bacterial infections pose a considerable threat to skin wounds, particularly in the case of challenging-to-treat diabetic wounds. Systemic antibiotics often struggle to penetrate deep wound tissues and topically applied antibiotics may lead to sensitization, necessitating the development of novel approaches for effectively treating germs in deep wound tissues. Neutrophils, the predominant immune cells in the bloodstream, rapidly release an abundance of molecules via degranulation upon activation, which possess the ability to directly eliminate pathogens. This study was designed to develop novel neutrophil cell engineered nanovesicles (NVs) with high production and explore their bactericidal properties and application in promoting infectious wound healing. Neutrophils were isolated from peripheral blood and activated in vitro via phorbol myristate acetate (PMA) stimulation. Engineered NVs were prepared by sequentially extruding activated neutrophils followed by ultracentrifugation and were compared with neutrophil-derived exosomes in terms of morphology, size distribution and protein contents. The bactericidal effect of NVs in vitro was evaluated using the spread plate technique, LIVE/DEAD backlight bacteria assay and observation of bacterial morphology. The therapeutic effects of NVs in vivo were evaluated using wound contraction area measurements, histopathological examinations, assessments of inflammatory factors and immunochemical staining. Activated neutrophils stimulated with PMA in vitro promptly release a substantial amount of bactericidal proteins. NVs are similar to exosomes in terms of morphology and particle size, but they exhibit a significantly higher enrichment of bactericidal proteins. In vitro, NVs demonstrated a significant bactericidal effect, presumably mediated by the enrichment of bactericidal proteins such as lysozyme. These NVs significantly accelerated wound healing, leading to a marked reduction in bacterial load, downregulation of inflammatory factors and enhanced collagen deposition in a full-thickness infectious skin defect model. We developed engineered NVs derived from activated neutrophils to serve as a novel debridement method targeting bacteria in deep tissues, ultimately promoting infectious wound healing.

Yüksek yağlı diyet ile beslenen ve tam kalınlıkta deri defekti modeli oluşturulan sıçanlarda laktoferrinin etkisi

Purpose: Lactoferrin is a member of the milk protein family with a broad spectrum of bioactivities and has therapeutic effects against many microbes, viruses, and other pathogens. This study aims to show the healing effect of lactoferrin against obesity-related wound healing.&#x0D; Materials and Methods: In this study, 48 male rats were grouped as the Control (C) (n =8), Full-thickness skin defect model (FT) (n =8), Bovine Lactoferrin (bLf) (200 mg/kg)(n= 8), High Fat Diet (HFD) + Bovine Lactoferrin (bLf) (n = 8), High-Fat Diet (HFD)+Full-thickness skin defect model (FT) (n=8), and HFD+Full-thickness skin defect model (FT) + Bovine Lactoferrin bLf (n=8). High-Fat Diet + bLf and High-Fat Diet + Full-thickness skin defect + bLf group rats were given a high-fat diet and Bovine Lactoferrin orally. IL-6 and VEGF biochemical parameters were examined in serum.&#x0D; Results: When the serum IL-6 protein amounts of the groups were examined, it was the highest in the HFD+FT+bLf group on the 21st day, and the lowest in the FT group, when the serum VEGF protein amounts, which were the other biochemical parameters, were evaluated, these amounts were found to be the highest in the HFD+FT+bLf group and the lowest in the FT group on the 21st day.&#x0D; Conclusion: Lactoferrin has been shown to accelerate wound healing, and the fact that lactoferrin is readily available and abundant in milk makes it an exciting treatment option for wound healing and inflammation in the future.

Bioinspired Zn-MOF doped radial porous chitosan-based sponge with antibacterial and antioxidant properties for rapid hemostasis and wound healing

Herein, a novel bioinspired radial porous zinc-based metal-organic framework (Zn-MOF) doped sodium alginate/chitosan derivatives/pullulan-based SA/PSCS/Pul/Zn-MOF (SPCP/Zn) composites sponge with excellent antioxidant and antibacterial properties was fabricated by the ice-templating method. Boric acid (BA) and Ca2+, which were respectively used as hydrogen- and ionic- bonding cross-linkers, provided strong mechanical properties for sponge matrix composed of SA, PSCS, and Pul. The obtained SPCP/Zn sponge exhibited uniform porous morphology, proper hydrophilicity, and admirable biocompatibility. In addition, the SPCP/Zn sponge achieved a sustained release of Zn2+ and gallic acid, which displayed powerful antibacterial and antioxidant activities. Importantly, the SPCP/Zn sponge exhibited shorter rapid hemostasis (20.4 ± 2.9 s) and lower blood loss (19.8 ± 4.3 mg). The SPCP/Zn sponge also showed faster wound closure ratio for the rat full-thickness skin defect model. It was revealed that SPCP/Zn sponge could significantly accelerate and enhance wound healing through downregulating inflammatory cytokines (TNF-α, IL-6) and increasing the expression of growth factors (VEGF). Due to its excellent properties, the SPCP/Zn sponge may have promising potential in wound healing applications.

Muscle-inspired lamellar chitosan sponge with photothermal antibacterial and antioxidant properties for hemostasis and accelerated bacteria infected wound healing

Wound dressings with excellent hemostasis, antibacterial, and antioxidant properties are essential for hemorrhagic infected wounds. Herein, inspired by the highly anisotropic and ordered fibrous structure of muscle tissue, we prepared chitosan/polydopamine biomimetic layered sponge dressings loaded with cerium dioxide (CeO2) nanoparticles by a directional freezing method. This composite sponge has an ordered laminate structure, good mechanical properties, excellent moisture absorption, and swelling properties. Thanks to the introduction of PDA, the composite sponge has outstanding photothermal properties and effectively kills bacteria under 808 nm near-infrared (NIR) light. In addition, the CeO2 loaded in the composite sponge also has an excellent ROS scavenging capacity, which protects cells from oxidative stress damage. The rat tail amputation and liver hemostasis experiment proved that this layered sponge had good hemostasis performance. Furthermore, the full-thickness skin defect model infected with S. aureus demonstrated that the composite sponge accelerated wound closure, promoted collagen deposition, down-regulated pro-inflammatory factors (TNF-α), and up-regulated anti-inflammatory factors (IL-10) expression, ultimately promoting wound healing. All the results suggested that this bionic sponge with a directional layered structure has a preferable therapeutic effect on the healing of infected wounds and is expected to be a more advantageous wound dressing.

Bilayer wound dressing composed of asymmetric polycaprolactone membrane and chitosan-carrageenan hydrogel incorporating storax balsam

A comprehensive approach is needed to develop multifunctional wound dressing that is simple yet efficient. In this work, Liquidambar orientalis Mill. storax loaded hydroxyethyl chitosan (HECS)-carrageenan (kC) based hydrogel (HECS-kC) and polydopamine coated asymmetric polycaprolactone membrane (PCL-DOP) were used to develop a multifunctional and modular bilayer wound dressing. Asymmetric PCL-DOP membrane was prepared by non-solvent induced phase separation (NIPS) followed by polydopamine coating and demonstrated an excellent barrier against bacteria while allowing permeability for 5.45 ppm dissolved‑oxygen and 2130 g/m2 water vapor transmission in 24 h in addition to 805 kPa tensile strength. Storax loaded HECS-kC hydrogel, on the other hand, demonstrated a pH-responsive degradation and swelling to provide necessary conditions to facilitate wound healing. The hydrogels showed stretchability above 140 %, mild adhesive strength on sheep skin and PCL-DOP membrane, while the storax incorporation enhanced antibacterial and antioxidant activity. Furthermore, rat full-thickness skin defect model showed that the developed bilayer wound dressing could significantly facilitate wound healing compared to Tegaderm™ and control groups. This study shows that the bilayered wound dressing has the potential to be used as a simple and effective wound care system.

Dynamic Microenvironment-Adaptable Hydrogel with Photothermal Performance and ROS Scavenging for Management of Diabetic Ulcer.

Persistent bacterial infections and excessive oxidative stress prevent the healing of diabetic ulcers, leading to an increased disability rate. Current treatments fail to kill bacteria while simultaneously relieving oxidative stress. Herein, a dynamic microenvironment-adaptable hydrogel (BP@CAu) with photothermal performance and reactive oxygen species scavenging is presented for diabetic ulcer healing. This hydrogel prepared using a dynamic borate-ester could respond to acidity in the infection microenvironment for a controllable drug release. An excellent photothermal conversion effect was integrated in the hydrogel, which exhibited strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The hydrogel attenuated intracellular oxidative stress and inflammation and promoted cell migration. In a full-thickness skin defect model of diabetic rats, the BP@CAu hydrogel contributed to the fastest wound closure, with ideal reepithelialization, granulation tissue formation, and regeneration of blood vessels. Further mechanistic studies revealed that the hydrogel relieved oxidative stress and downregulated the expression of inflammatory cytokines, resulting in dramatic therapeutic effects on diabetic wounds. Therefore, this study provides a synergistic therapeutic strategy for efficient photothermal performance and reactive oxygen species scavenging in diabetic ulcers.