Rat Full-thickness Wound Model Research Articles

Programming of macrophage polarization in different stages for accelerating wound healing

Macrophage polarization and phenotypic switching have a significant impact on the immune microenvironment of wounds, making them crucial for wound healing. Creating immune-adapted microenvironment throughout the wound repair process by regulating macrophage polarization supports rapid wound healing. We explored the segmented use of M1-polarizing and M2-polarizing materials at different healing stages and found that this combination can significantly shorten the healing time. The macrophage polarization could be adjusted to M1 phenotype and M2 phenotype by selective modification of chitosan with dicyandiamide or polyethylene glycol, respectively. In a rat full-thickness infected wound model, combining dicyandiamide modified chitosan (DICY-CS) for M1 macrophage polarization in the inflammatory phase and PEGylated chitosan (PEG-CS) for M2 macrophage polarization in the proliferative phase significantly reduced wound healing time. A higher degree of re-epithelialization, collagen deposition and neovascularization were observed in wounds treated with this combination approach compared to the antimicrobial agents Silvadene and DICY-CS or PEG-CS alone. The use of different macrophage polarizing materials separately in different healing stages provided an optimal immune microenvironment and accelerated wound healing. This strategy provides a more comprehensive understanding of the wound healing process. It will be a new insight for the treatment of more complex and difficult-to-heal wounds such as pressure ulcers and diabetic wounds.

Exosome-coated oxygen nanobubble-laden hydrogel augments intracellular delivery of exosomes for enhanced wound healing

Wound healing is an obvious clinical concern that can be hindered by inadequate angiogenesis, inflammation, and chronic hypoxia. While exosomes derived from adipose tissue-derived stem cells have shown promise in accelerating healing by carrying therapeutic growth factors and microRNAs, intracellular cargo delivery is compromised in hypoxic tissues due to activated hypoxia-induced endocytic recycling. To address this challenge, we have developed a strategy to coat oxygen nanobubbles with exosomes and incorporate them into a polyvinyl alcohol/gelatin hybrid hydrogel. This approach not only alleviates wound hypoxia but also offers an efficient means of delivering exosome-coated nanoparticles in hypoxic conditions. The self-healing properties of the hydrogel, along with its component, gelatin, aids in hemostasis, while its crosslinking bonds facilitate hydrogen peroxide decomposition, to ameliorate wound inflammation. Here, we show the potential of this multifunctional hydrogel for enhanced healing, promoting angiogenesis, facilitating exosome delivery, mitigating hypoxia, and inhibiting inflammation in a male rat full-thickness wound model.

Preparation and characterization of chitosan/polyvinyl alcohol antibacterial sponge materials

This study utilized the freeze-drying method to create a chitosan (CS) and polyvinyl alcohol (PVA) sponge. To enhance its antibacterial properties, curcumin and nano silver (Cur@Ag) were added for synergistic antibacterial. After adding curcumin and nano silver, the mechanical properties of the composite sponge dressing (CS-PVA-Cur@Ag) were improved. The porosity of the composite sponge dressing was closed to 80%, which was helpful for drug release, and it had good water absorption and water retention rate. The nano silver diameter was 50–80 nm, which was optimal for killing bacteria. Antibacterial tests used Escherichia coli and Staphylococcus aureus demonstrated that little nano silver was required to eliminate bacteria. Finally, in the rat full-thickness skin wound model, the composite sponge dressing can promote wound healing in a short time. In summary, CS-PVA-Cur@Ag wound dressing could protect from bacterial infection and accelerate wound healing. Thus, it had high potential application value for wound dressing.

All-in-One Self-Powered Microneedle Device for Accelerating Infected Diabetic Wound Repair.

Diabetic wound healing remains a significant clinical challenge due to the complex microenvironment and attenuated endogenous electric field. Herein, a novel all-in-one self-powered microneedle device (termed TZ@mMN-TENG) is developed by combining the multifunctional microneedle carried tannin@ZnO microparticles (TZ@mMN) with the self-powered triboelectric nanogenerator (TENG). In addition to the delivery of tannin and Zn2+ , TZ@mMN also effectively conducts electrical stimulation (ES) to infected diabetic wounds. As a self-powered device, the TENG can convert biomechanical motion into exogenous ES to accelerate the infected diabetic wound healing. In vitro experiment demonstrated that TZ@mMN shows excellent conductive, high antioxidant ability, and effective antibacterial properties against both Staphylococcus aureus and Escherichia coli (>99% antibacterial rates). Besides, the TZ@mMN-TENG can effectively promote cell proliferation and migration. In the diabetic rat full-thickness skin wound model infected with Staphylococcus aureus, the TZ@mMN-TENG can eliminate bacteria, accelerate epidermal growth (regenerative epidermis: ≈303.3 ± 19.1µm), enhance collagen deposition, inhibit inflammation (lower TNF-α and IL-6 expression), and promote angiogenesis (higher CD31 and VEGF expression) to accelerate infected wound repair. Overall, the TZ@mMN-TENG provides a promising strategy for clinical application in diabetic wound repair.

In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles.

Interactive wound dressings have displayed promising outcomes in enhancing the wound healing process. This study focuses on creating a nanocomposite wound dressing with interactive and bioactive properties, showcasing potent antioxidant effects. To achieve this, we developed cerium oxide nanoparticles utilizing curcumin as both the reducing and capping agent. Characterization techniques such as SEM, EDX, DLS, Zetasizer, FTIR, and XRD were utilized to analyze the cerium oxide nanoparticles synthesized through a green approach. The image analysis on the obtained TEM images showed that the curcumin-assisted biosynthesized CeO2NPs have a size of 18.8 ± 4.1nm. The peaks located at 28.1, 32.7, 47.1, 56.0, 58.7, 69.0, and 76.4 correspond to (111), (200), (220), (311), (222), (400), and (331) crystallographic planes. We applied the Debye-Scherrer equation and observed that the approximate crystallite size of the biosynthesized NPs is around 8.2nm based on the most intensive broad Bragg peak at 28.1°. The cerium oxide nanoparticles synthesized were integrated into an alginate hydrogel matrix, and the microstructure, porosity, and swelling behavior of the resulting wound dressing were assessed. The characterization analyses provided insights into the physical and chemical properties of the green-synthesized cerium oxide nanoparticles and the alginate hydrogel-based wound dressing. In vitro studies demonstrated that the wound dressing based on alginate hydrogel exhibited favorable antioxidant properties and displayed hemocompatibility and biocompatibility. Animal studies conducted on a rat full-thickness skin wound model showed that the alginate hydrogel-based wound dressing effectively accelerated the wound healing process. Overall, these findings suggest that the alginate hydrogel-based wound dressing holds promise as a highly effective material for wound healing applications.

Injectable hydrogel based on silk fibroin/carboxymethyl cellulose/agarose containing polydopamine functionalized graphene oxide with conductivity, hemostasis, antibacterial, and anti-oxidant properties for full-thickness burn healing

Overcoming bacterial infections and promoting wound healing are significant challenges in clinical practice and fundamental research. This study developed a series of enzymatic crosslinking injectable hydrogels based on silk fibroin (SF), carboxymethyl cellulose (CMC), and agarose, with the addition of polydopamine functionalized graphene oxide (GO@PDA) to endow the hydrogel with suitable conductivity and antimicrobial activity. The hydrogels exhibited suitable gelation time, stable mechanical and rheological properties, high water absorbency, and hemostatic properties. Biocompatibility was also confirmed through various assays. After loading the antibiotic vancomycin hydrochloride, the hydrogels showed sustained release and good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The fast gelation time and desirable tissue-covering ability of the hydrogels allowed for a good hemostatic effect in a rat liver trauma model. In a rat full-thickness burn wound model, the hydrogels exhibited an excellent treatment effect, leading to significantly enhanced wound closure, collagen deposition, and granulation tissue formation, as well as neovascularization and anti-inflammatory effects. In conclusion, the antibacterial electroactive injectable hydrogel dressing, with its multifunctional properties, significantly promoted the in vivo wound healing process, making it an excellent candidate for full-thickness skin wound healing.

Beneficial Effects of Dinitrosyl Iron Complexes on Wound Healing Compared to Commercial Nitric Oxide Plasma Generator.

Nitric oxide (NO) is a gaseous molecule which plays a key role in wound healing. Previously, we identified the optimal conditions for wound healing strategies using NO donors and an air plasma generator. The aim of this study was to compare the wound healing effects of binuclear dinitrosyl iron complexes with glutathione (B-DNIC-GSH) and NO-containing gas flow (NO-CGF) at their optimal NO doses (0.04 mmol for B-DNIC-GSH and 1.0 mmol for NO-CGF per 1 cm2) in a rat full-thickness wound model over a 3-week period. Excised wound tissues were studied by light and transmission electron microscopy and immunohistochemical, morphometrical and statistical methods. Both treatments had an identical stimulating impact on wound healing, which indicated a higher dosage effectiveness of B-DNIC-GSH compared to the NO-CGF. B-DNIC-GSH spray application reduced inflammation and promoted fibroblast proliferation, angiogenesis and the growth of granulation tissue during the first 4 days after injury. However, prolonged NO spray effects were mild compared to NO-CGF. Future studies should determine the optimal B-DNIC-GSH solution course for a more effective wound healing stimulation.

The preparation of lactoferrin/magnesium silicate lithium injectable hydrogel and application in promoting wound healing

The development of novel wound dressings with highly effective antibacterial and accelerating wound healing properties has become the focus of current research. In this study, a novel and injectable lactoferrin (LF)/lithium magnesium silicate hydrogel (LMSH) was first synthesized through a simple electrostatic interaction method. The physical and biological properties are systematically characterized. The results show that the synthesized LF/LMSH has good antibacterial properties and biocompatibility. More importantly, it can effectively promote wound healing in the rat full-thickness skin wound model after 14 days post-operation, and the healing rate can reach 99.1 %, which is much higher than that of other groups. Meanwhile, histochemical and immunofluorescent staining confirm that the prepared injectable LF/LMSH has good pro-collagen deposition, pro-angiogenic and anti-inflammatory properties. The healed wounds present a consistently thickened epidermis with more follicular and glandular structures, indicating the great potential of the prepared material for wound management.

Phase-change composite filled natural nanotubes in hydrogel promote wound healing under photothermally triggered drug release.

It is of great importance to treat a bacterial-infected wound by a smart dressing capable of delivering antibiotics in a smart manner without causing drug resistance. The construction of smart release nanocontainers responsive to near-infrared (NIR) laser irradiation in an on-demand and stepwise way is a promising strategy for avoiding the emergence of multidrug-resistant bacteria. Here, we develop a hydrogel composite made of alginate and nanotubes with an efficient NIR-triggered release of rifampicin and outstanding antibacterial ability. This composite hydrogel is prepared through co-encapsulating antibacterial drug (rifampicin), NIR-absorbing dye (indocyanine green), and phase-change materials (a eutectic mixture of fatty acids) into halloysite nanotubes, followed by incorporation into alginate hydrogels, allowing the in-situ gelation at room temperature and maintaining the integrity of drug-loaded nanotubes. Among them, the eutectic mixture with a melting point of 39 °C serves as the biocompatible phase-change material to facilitate the NIR-triggered drug release. The resultant phase-change material gated-nanotubes exhibit a prominent photothermal efficiency with multistep drug release under laser irradiation. In an in vitro assay, composite hydrogel provides good antibacterial potency against Staphylococcus aureus, one of the most prevalent microorganisms of dangerous gas gangrene. A bacterial-infected rat full-thickness wound model demonstrates that the NIR-responsive composite hydrogel inhibits the bacteria colonization and suppresses the inflammatory response caused by bacteria, promoting angiogenesis and collagen deposition to accelerate wound regeneration. The NIR-responsive composite hydrogel has a great potential as an antibacterial wound dressing functionalized with controlled multistep treatment of the infected sites.

Construction of chitosan-based asymmetric antioxidant and anti-inflammatory repair film for acceleration of wound healing

Oxidative stress damage caused by free radicals around the moist microenvironment of wound has been a clinical challenge in skin tissue healing. Here, a novel chitosan-based bioinspired asymmetric wound repair composite (BAWRC) film was designed by facilitated endogenous tissue engineering strategy through layer-by-layer self-assembly technology for accelerated wound healing. The asymmetric characteristics were skillfully reflected by two different functional layers: hydrophilic chitosan (CS)/silk fibroin (SF) repair layer, and a hydrophobic bacteriostatic tea tree oil (TTO) layer with a rough surface. Simultaneously, sodium ascorbate (SA)-entrapped poly (lactic-co-glycolic acid) (PLGA) microspheres are distributed homogeneously in the hydrophilic layer to induce antioxidant response for skin repair. The distinctive asymmetric structure of BAWRC film endows it with synergistic effects, i.e., protects against the risk of infection from the external environment and facilitates deep skin wound healing. Results show that the minimum inhibition and bactericidal concentration of the BAWRC film were 1.25 and 6.25 mg/mL, respectively, demonstrating good antibacterial properties. The content of biofilm formation was significantly reduced when the concentration of TTO exceeds 5 mg/mL, indicating TTO shows a positive effect on bacteriostasis. In addition, the DPPH rates of BAWRC film were up to 64.7 % after incubation for 12 h, which was ascribed to that the release of SA and TTO as a natural product could accelerate free radical scavenging. The BAWRC film exhibited excellent biocompatibility, and good antibacterial capacity, enhancing adhesion and proliferation of the NIH3T3 cell in vitro, further facilitating the healing of a rat full-thickness skin wounds model. Herein, this versatile asymmetric film possesses great potential for clinical management of wound healing and related soft tissue regeneration.

Total alkaloid fraction of Leonurus japonicus Houtt. Promotes angiogenesis and wound healing through SRC/MEK/ERK signaling pathway

Ethnopharmacological relevanceLeonurus japonicus Houtt., also known as motherwort, is a traditional Chinese medicine that was first identified in Shennong Bencao Jing, the first and essential pharmacy monograph in China. L. japonicus has been regarded as a good gynecological medicine since ancient times. It has been widely used in clinical settings for treatment of gynecological diseases and postnatal rehabilitation with good efficacy and low adverse effects. Aim of the studyThe main purpose of this study was to determine the angiogenic and wound healing effects of total alkaloid fraction from L. japonicus Houtt. (TALH) in vivo and in vitro. In addition, the main bioactive components of total alkaloids were to be identified and analyzed in this study. Materials and methodsFirst, the UHPLC/Q-TOF-MS method was used to identify and quantify the major components in the TALH extract. The wound healing activity was evaluated in vivo using a rat full-thickness cutaneous wound model. Histological study of wound healing in rat model was performed via immunohistochemistry and immunofluorescence. Cell proliferation was determined by MTT assay. Wound healing and transwell assays were used for detection of cell migration. The effect on tube formation was determined by tube formation assay in HUVECs. Western blot and RT-PCR were used to detect the expressions of relative proteins and genes respectively. Knock-down of SRC by siRNA was done to verify the crucial role of SRC in promotion of angiogenesis induced by TALH. ResultsSeven characteristic peaks were recognized in the UHPLC/Q-TOF-MS spectrum, while four of the main components were quantified. The wound model in rats showed that treatment of TALH promoted wound healing by stimulating cellular proliferation and collagen deposition. In vitro experiments showed that co-treatment of TALH and VEGF increased cell proliferation, migration and tube formation in HUVECs. Mechanistic studies suggested that the co-treatment increased gene expressions of SRC, MEK1/2 and ERK1/2, as well as the phosphorylation levels of these proteins. Furthermore, the effect of co-treatment was attenuated after SRC knockdown, suggesting that SRC plays an important role in angiogenesis and wound healing induced by TALH and VEGF co-treatment. ConclusionOur results showed that TALH was one of the main active components of L. japonicus that promoted angiogenesis and wound healing by regulating the SRC/MEK/ERK pathway. Our study provided scientific basis for better clinical application of L. japonicas.

Mussel-inspired adhesive gelatin-polyacrylamide hydrogel wound dressing loaded with tetracycline hydrochloride to enhance complete skin regeneration.

Even though the global wound care market size was valued at USD 19.83 billion in 2020, it is still a challenge to develop a hydrogel-based wound dressing with a good mechanical property, adhesiveness and antibacterial property. This study established and validated a mussel-inspired adhesive hydrogel wound dressing with antibacterial activity by dispersing tetracycline hydrochloride into hydrogel based polydopamine, gelatin and polyacrylamide. A tough hydrogel with a fracture stress of 0.42 MPa was prepared by changing the contents of the gelatin and polyacrylamide. With the addition of polydopamine and tetracycline hydrochloride, the hydrogel was endowed with an adhesive property (with a tissue adhesive strength of 4.13 kPa) and antibacterial activity against both Escherichia coli and Staphylococcus aureus. Finally, a rat full-thickness skin defect wound model was used to evaluate the performance of the hydrogels in wound repair. The hydrogel group showed a significantly reduced wound area (95.72%) compared with the blank group (86.34%) on day 14. The hydrogel promoted the collagen deposition, weakened the inflammatory response and enhanced wound healing. Therefore, the hydrogel with multifunctional properties is a promising candidate for complete skin regeneration.

Controlled pVEGF delivery via a gene-activated matrix comprised of a peptide-modified non-viral vector and a nanofibrous scaffold for skin wound healing

Regulating cell function and tissue formation by combining gene delivery with functional scaffolds to create gene-activated matrices (GAMs) is a promising strategy for tissue engineering. However, fabrication of GAMs with low cytotoxicity, high transfection efficiency, and long-term gene delivery properties remains a challenge. In this study, a non-viral DNA delivery nanocomplex was developed by modifying poly (D, L-lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) nanoparticles with the cell-penetrating peptide KALA. Subsequently, the nanocomplex carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF) was immobilized onto a polydopamine-coated electrospun alginate nanofibrous scaffold, resulting in a GAM for enhanced skin wound healing. The nanocomplex exhibited much lower cytotoxicity and comparable or even higher transfection efficiency compared with PEI. The GAM enabled sustained gene release and long-tern transgene expression of VEGF in vitro. In an excisional full-thickness skin wound rat model, the GAM could accelerate wound closure, promote complete re-epithelization, reduce inflammatory response, and enhance neovascularization, ultimately enhancing skin wound healing. The current GAM comprising a low-toxic gene delivery nanocomplex and a biocompatible 3D nanofibrous scaffold demonstrates great potential for mediating long-term cell functions and may become a powerful tool for gene delivery in tissue engineering. Statement of significanceGene delivery is a promising strategy in promoting tissue regeneration as an effective alternative to growth factor delivery, but the study on three-dimensional gene-activated scaffolds remains in its infancy. Herein, a biodegradable nanofibrous gene-activated matrix integrating non-viral nanoparticle vector was designed and evaluated both in vitro and in vivo. The results show that the nanoparticle vector provided high transfection efficiency with minimal cytotoxicity. After surface immobilization of the nanocomplexes carrying plasmid DNA encoding vascular endothelial growth factor (pVEGF), the nanofibrous scaffold enabled sustained DNA release and long-term transgene expression in vitro. In a rat full-thickness skin wound model, the scaffold could accelerate wound healing. This innovative gene-activated matrix can be a promising candidate for tissue regeneration.

Novel hybrid scaffold for improving the wound repair process: evaluation of combined chitosan/eggshell/vitamin D scaffold for wound healing

The current design requirement of cutaneous wound healing is an ideal wound dressing via biodegradable property through which fibroblasts can support, migrate and proliferate. This study aimed to evaluate the effect of the synthesized hybrid scaffold based on chitosan polymer and a natural source of calcium (Ca) and vitamin D on wound healing. To achieve this purpose, three scaffolds include in chitosan (CS), eggshell + chitosan (ES/CS) and chitosan + eggshell + vitamin D (CS/ES/Vit D) were fabricated using the freeze-drying approach. Synthesized scaffolds were characterized by field emission scanning electron microscopy (FESEM), Fourier transformed infrared (FTIR), X-ray diffraction (XRD) and MTT assay. Histological examinations of the wound healing were performed using hematoxylin–eosin (H&E) and Masson's trichrome staining methods on different days in the rat full-thickness skin wound model. Finally, the effect of the synthesized scaffold was evaluated on the TGF-β1 gene expression. The results of the scaffold characterization showed that scaffolds have the homogeneity structure. The MTT assay indicated that the cultured fibroblasts on the ES/CS and Vit D/ES/CS scaffold had viability higher than those cultured on CS. Also, histological studies demonstrated an increased effect on epithelialization and collagen production and accelerated wound healing using designed scaffolds. The TGF-β1 gene expression in all scaffolds was not significantly different between test groups and controls. In general, it can be concluded that the synthesized scaffolds have the potential to accelerate wound healing and can be used as a suitable scaffold in wound management and skin regeneration.

Chitosan/alginate/hyaluronic acid polyelectrolyte composite sponges crosslinked with genipin for wound dressing application

Wound dressing composed of polyelectrolyte complexes (PECs), based on chitosan/alginate/hyaluronic acid (CS/ALG/HYA) crosslinked by genipin, was prepared by freeze-dried molding. Genipin as excellent natural biological crosslinker was chose for high biocompatibility and improving mechanical properties of materials. The CS/ALG/HYA sponges (CAHSs) were characterized by FTIR, XRD, DSC and SEM. Porosity, swelling behavior and mechanical properties and in vitro degradation of CAHSs were investigated. The cytotoxicity assay was carried out on HUVEC cells in vitro and the result proves the good biocompatibility of CAHSs. Hemolysis tests indicated that the prepared CAHSs were non-hemolytic material (hemolysis ratio < 5%, no cytotoxicity). PT and aPPT coagulation tests demonstrated that CAHS2 and CAHS3 could both activate the extrinsic and intrinsic coagulation pathway and thus accelerated blood coagulation. Further, in a rat full-thickness wounds model, the CAHS2 sponge significantly facilitates wound closure compared to other groups. CAHSs exhibited adjustable physical, mechanical and biological properties. Thus, the chitosan-based polyelectrolyte composite sponges exhibit great potential as promising wound dressings.

Topical effect of benzalkonium bromide on wound healing and potential cellular and molecular mechanisms

Benzalkonium bromide (BB) has been widely used as a skin antiseptic for wound management. However, BB had proinflammation and reactive oxygen species (ROS) induction effect, making its role in wound healing complex and unclear. A rat full‐thickness skin defect wound model was established. The effects of BB, povidone iodine (PVP‐I), chlorhexidine gluconate (CHG), and normal saline (NS) on wound healing and infection control were then evaluated based on wound healing rate (WHr) and bacterial killing. The wound tissues were sectioned for histopathological evaluation and nuclear factor E2 related factor 2 (Nrf2) expression determination. The ROS production, Nrf2 activation, and heme oxygenase 1 (HO‐1) expression of the HaCat cells and the cytotoxicity treated with BB were further explored. Compared with NS, PVP‐I, and CHG, BB showed the best wound infection control efficiency while delayed wound healing with the WHr of 91.42 ± 5.12% at day 20. The wound tissue of the BB group showed many inflammatory cells but few granulation tissue and capillaries and no obvious collagen deposition, resulting in the lowest histopathological scores of 4.17 ± 0.75 for BB group. BB showed higher cytotoxicity on HaCat cells with the lowest IC25, IC50, and IC75 of 1.90, 4.16, and 9.09 g/mL compared with PVP‐I and CHG. TUNEL staining evaluated the cytotoxicity of BB on wound tissue, which indicates the high apoptosis index BB group (5.05 ± 1.77). Compared with PVP‐I and CHG, BB induced much more cell apoptosis. The results of flow cytometry and fluorescence staining showed that PVP‐I, CHG, and BB induced ROS production in a concentration‐dependent manner and cells treated with BB had the highest ROS production at the same inhibition concentration. The cells and the wound tissues treated with BB showed highest Nrf2 activation and HO‐1 expression than PVP‐I and CHG. BB was highly efficient in wound infection control while delayed wound healing. The prolonged and strengthened inflammation and the raised ROS production originating from BB administration may contribute to delayed wound healing.

A biodegradable antibacterial alginate/carboxymethyl chitosan/Kangfuxin sponges for promoting blood coagulation and full-thickness wound healing

Conventional wound-dressing materials with structural and functional deficiencies are not effective in promoting wound healing. The development of multifunctional wound dressings is emerging as a promising strategy to accelerate blood coagulation, inhibit bacterial infection, and trigger full-thickness wound into a regenerative process. Herein, multifunctional composite sponges were developed by incorporation of traditional Chinese medicine Kangfuxin (KFX) into alginate (AG)/carboxymethyl chitosan (CMC) via green crosslinking, electrostatic interaction, and freeze-drying methods. It is demonstrated that the AG/CMC/KFX (ACK) sponges exhibit a highly interconnected and porous structure, suitable water vapor transmittance, excellent elastic properties, antibacterial behavior, cytocompatibility, and rapid hemostasis. Further, in a rat full-thickness wounds model, the ACK sponge containing 10% KFX (ACK-10) significantly facilitates wound closure compared to the AC group and ACK sponge containing 5% and 15% KFX. Thus, the multifunctional ACK-10 composite sponge has great promise for the application of full-thickness wound healing.

Green fabrication of seedbed-like Flammulina velutipes polysaccharides–derived scaffolds accelerating full-thickness skin wound healing accompanied by hair follicle regeneration

A novel seedbed-like scaffold was firstly fabricated by the “frozen sectioning” processing method using Flammulina velutipes as a raw material. The Flammulina velutipes polysaccharides scaffold is composed of a natural structure imitating the “ground” (connected and aligned hollow tubes with porous walls). Meanwhile, its biologically active components include polysaccharides and proteins, mimicking the “plant nutrition” in the seedbed. To further optimize the ground and nutrition components, Flammulina velutipes polysaccharides–derived scaffolds (FPDSs) were fabricated via the treatment of original Flammulina velutipes polysaccharides scaffold (labeled FPS) by NaOH, cysteine (labeled as FPS/NaOH, FPS/Cys, respectively). FPDSs were characterized by SEM, FTIR, XRD, water absorption and retention, and mechanical evaluations. From the results, FPS/NaOH and FPS/Cys lost the characteristic big tubes of original strips and had higher water absorption capacities comparing to FPS. Simultaneously, FPS/NaOH had better ductility, FPS/Cys had showed increased stiffness. Biological activities of FPDSs were tested against different types of bacteria exhibiting excellent anti-bacterial activity, and FPS/NaOH and FPS/Cys had dramatically higher anti-bacterial activity than FPS. The cytocompatibility of FPDSs was evaluated utilizing mouse fibroblast cell line (L929), and all FPDSs showed good cytocompatibility. The FPDSs were further applied to a rat full-thickness skin wound model, and they all exhibited obviously accelerated re-epithelialization, among which FPS/NaOH showed the greatest efficiency. FPS/NaOH could shorten the wound-healing process as evidenced by dynamic alterations of the expression levels of specific stagewise markers in the healing areas. Similarly, FPS/NaOH can efficiently induce hair follicle regeneration in the healing skin tissues. In summary, FPDSs exhibit potential functions as seedbeds to promote the regeneration of the “seed” including hair follicles and injured skin, opening a new avenue for wound healing.

Piezoelectric and photothermal dual functional film for enhanced dermal wound regeneration via upregulation of Hsp90 and HIF-1α

Skin wounds, especially chronic wounds such as pressure and diabetic ulcers, are posing a huge threat to healthcare systems worldwide. Thus, novel strategies to realize effective wound therapy are nowadays extremely needed. Herein, we are the first to report a combination therapy of electric stimulation and heat for wound healing just using a facile piezoelectric and photothermal dual functional film. The film, name as CM@DA, is simply fabricated by coating polydopamine on a chitosan film. CM@DA generates electric voltages under mechanical pressure and shows photothermal effect with irradiation of near-infra red (NIR) light. In vivo experiment with rat full-thickness wound model validates that CM@DA with NIR can effectively promote wound regeneration due to the generation of electric stimulation and heat on wounds. The healing mechanism of CM@DA is further investigated, and the result demonstrates that CM@DA enhances wound healing through a pathway in which heat shock protein 90 (Hsp90) and hypoxia-inducible factor 1α (HIF-1α) participate. These results indicate that CM@DA is a promising wound dressing candidate for clinical application in the future.

Zinc sulfide nanoparticles improve skin regeneration

Wound healing has been intensely studied to expedite recovery times and reduce scarring. However, current technologies fail to achieve regenerative capabilities, leaving wounds with scarring and lack of skin accessories. The recent emergence of nanotechnology has provided a new clinical modality of zinc nanoparticles in wound care. This present study investigated Zinc Sulfide nanoparticles (ZnS-NP) on wound healing in vitro with 2D and 3D models and in vivo with rat full-thickness wound model. ZnS-NP inhibited fetal bovine serum-stimulated rat skin fibroblast cell proliferation, altered cytoskeletal organization, and reduced collagen synthesis as well as contractile activity. ZnS-NP regulated redox homeostatsis and promoted fibroblast viability in 3D hypoxia conditions. In the rat full-thickness wound model, ZnS-NP reduced wound contraction, enhanced re-epithelization, and promoted skin appendage formation. The biological activities of ZnS-NPs determined in our current study may suggest promising practical applications for topical or systemic treatment for wound repair.