Full-thickness Skin Wound Model Research Articles

Development and characterization of contraction-suppressed full-thickness skin wound model in rabbits

The wound healing process in rodents (rats and mice) and lagomorphs (rabbits) predominantly relies on wound contraction rather than re-epithelialization and granulation tissue formation. As a result, existing laboratory animal models for wound healing often fail to mimic human wound healing mechanisms accurately. This study introduces a standardized rabbit model with superior translational potential for skin wound healing research. Two full-thickness dermal wounds were created on the posterior dorsal surface of each rabbit using a standard 2 ×2 cm² template. One of these wounds was randomly selected to be treated as a contraction-suppressed wound by applying a transparent adhesive elastic bandage. At the same time, the other was retained as a standard full-thickness wound. Wound contraction was measured on 7, 14, 21, 28, and 35 days. Histomorphological evaluation was done on day 35 to evaluate the quality of wound healing. The findings indicate that transparent adhesive elastic bandage prolonged the wound healing time and suppressed wound contraction in rabbits. In addition, the healed contraction-suppressed full-thickness wounds had denser and thicker collagen fibers than the healed standard full-thickness wounds, indicating better collagen fiber deposition. Our model achieved a 100 % success rate in maintaining the transparent adhesive elastic bandage in the rabbits. Therefore, we have developed a simple, non-invasive, cost-effective method for preventing wound contraction. Further studies are required to establish the utility of this model for studying wound healing mechanisms and evaluating therapeutic interventions.

Developing multifunctional pectin-based hydrogel for wound dressing: In silico, in vitro and in vivo evaluation

Multifunctional hydrogel wound dressing with high hemostatic, antioxidant, and self-healing activity is desirable in clinical applications. In this contribution, we developed two distinct hydrogel formulations, namely PZ and PTBA, by employing low methoxyl pectin (P), zeolite, or 2-thiobarbituric acid (TBA) for sustained release of procaine (PC) in a controlled manner up to 40 h. These hydrogel systems (PZ and PTBA) utilize dynamic reversible hydrogen bonds between the components and a metal coordination bond between carboxyl acid groups of pectin chains and Ca2+ to confer self-healing properties, as demonstrated by molecular dynamics (MD) and rheological analyses. Moreover, PZ and PTBA hydrogels possess superior antioxidant, hemostasis, biocompatibility, and antibacterial activities. The data from the mouse skin incision model and infected full-thickness skin wound model demonstrated the highest wound closure rate (wound closure area per day) was achieved by the PZ (4.72) and PTBA (4.62) groups on day 21, which was better than the control (4.2) and Kaltostat groups (4.05) (p < 0.05). PZ and PTBA’s effectiveness in wound closure and acceleration of the wound healing process, highlighting its significant potential in wound management.

Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery

BackgroundThe non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs.ResultsThe DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice.ConclusionResults obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.Graphical

Light-controlled crosslinked multifunctional "Band-Aids" as dual-stage wound dressing for dynamic wound closure

The objective of regenerative wound healing dressings is to accelerate skin tissue regeneration and restore normal physiological function at wound sites. Achieving this goal requires biomaterials capable of repairing distinct phases of wound healing in a way that balances material function, degradation, safety, and tissue growth. In this study, we introduced a novel dual-stage wound dressing system comprising methacrylic anhydride-modified recombinant humanized type III collagen (rhCol III-MA) and methacrylic anhydride-modified dopamine (DMA) (RMDM), which was synthesized through free radical polymerization and π-π stacking. Within this system, RMDM was formulated into two forms with identical compositions: hydrogel and sponge, tailored for application across various stages of wound repair. These materials displayed favorable hemocompatibility, biocompatibility, antioxidant properties, and angiogenic potential in vitro. Moreover, the in vivo experiments also demonstrated that sponges could rapidly stop the bleeding of wounds in mouse tail amputation and liver incision models. Notably, the sponge/gel (S/G) system accelerated wound healing compared to individual sponge and gel treatments in a rat full-thickness skin wound model, underscoring the synergistic benefits of combining sponge and gel materials for wound repair at different stages. Therefore, this research provides valuable insights into designing advanced biomaterials that can be tailored to specific stages of wound healing, which may have significant potential for biomedical applications.Graphical

Quaternary ammonium carboxymethyl chitosan composite hydrogel with efficient antibacterial and antioxidant properties for promoting wound healing

Multifunctional hydrogels have been developed to meet the various requirements of wound healing. Herein, an innovative hydrogel (QCMC-HA-PEG) was formed through the Schiff base reaction, composed of quaternary ammonium-modified carboxymethyl chitosan (QCMC), hyaluronic acid (HA), and 8-arms Polyethylene Glycol aldehyde (8-ARM-PEG-CHO). The resulting hydrogels exhibited good mechanical and adhesive properties with improved antibacterial efficacy against both Gram-positive and Gram-negative bacteria compared to CMC hydrogels. QCMC-HA-PEG hydrogels demonstrated remarkable adhesive ability in lap-shear test. Furthermore, the incorporation of MnO2 nanosheets into the hydrogel significantly enhanced its reactive oxygen species (ROS) scavenging and oxygen generation capabilities. Finally, experimental results from a full-thickness skin wound model revealed that the QCMC-HA-PEG@MnO2 hydrogel promoted skin epithelization, collagen deposition, and inflammatory regulation significantly accelerated the wound healing process. Therefore, QCMC-HA-PEG@MnO2 hydrogel could be a promising wound dressing to promote wound healing.

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.

Copper Ion-Inspired Dual Controllable Drug Release Hydrogels for Wound Management: Driven by Hydrogen Bonds.

Bacterial infections and inflammation progression yield huge trouble for the management of serious skin wounds and burns. However, some hydrogel dressing exhibit poor wound-healing capabilities. Additionally, little information is given on the molecular theory of hydrogel gelation mechanisms and drug release performance from drug-polymer network in the water environment. Herein, cationic guar gum (CG) is first mixed with dipotassium glycyrrhizinate (DG), and then crosslinked Cu2+ to strengthen the mechanical strength followed by encapsulating mussel adhesive protein (MAP) as composite dressings. Intriguingly, CG-Cu2+ 0.5-DG10 possessed proper rheological properties and mechanical strength predominantly driven by strong CG-H2O-Cu2+ and Cu2+-CG hydrogen bonding interaction. Weak DG-CG hydrogen bonding only controlled DG release in the initial 4 h, while strong hydrogen bonding is the main force regulating the sustained release of Cu2+ within 48 h. The incorporation of MAP further loosened the tight crosslinking of CG-Cu2+ 0.5-DG10. The screened CG-Cu2+ 0.5-DG10/MAP possessed excellent self-healing, injectability, antibacterial, anti-inflammatory, cell proliferation-promotion activities with high biocompatibility. Therefore, CG-Cu2+ 0.5-DG10/MAP hydrogel expedited wound closure on S. aureus-infected full-thickness skin wound model and lowered necrosis progression to the unburned interspaces on a rat burn model. The results highlight the promising translational potential of Cu2+-inspired hydrogels for the management of burns and infected wounds.

Adipose-derived stem cells derived decellularized extracellular matrix enabled skin regeneration and remodeling.

The tissues or organs derived decellularized extracellular matrix carry immunogenicity and the risk of pathogen transmission, resulting in limited therapeutic effects. The cell derived dECM cultured in vitro can address these potential risks, but its impact on wound remodeling is still unclear. This study aimed to explore the role of decellularized extracellular matrix (dECM) extracted from adipose derived stem cells (ADSCs) in skin regeneration. Methods: ADSCs were extracted from human adipose tissue. Then we cultivated adipose-derived stem cell cells and decellularized ADSC-dECM for freeze-drying. Western blot (WB), enzyme-linked immunosorbent assay (ELISA) and mass spectrometry (MS) were conducted to analyzed the main protein components in ADSC-dECM. The cell counting assay (CCK-8) and scratch assay were used to explore the effects of different concentrations of ADSC-dECM on the proliferation and migration of human keratinocytes cells (HaCaT), human umbilical vein endothelia cells (HUVEC) and human fibroblasts (HFB), respectively. Moreover, we designed a novel ADSC-dECM-CMC patch which used carboxymethylcellulose (CMC) to load with ADSC-dECM; and we further investigated its effect on a mouse full thickness skin wound model. Results: ADSC-dECM was obtained after decellularization of in vitro cultured human ADSCs. Western blot, ELISA and mass spectrometry results showed that ADSC-dECM contained various bioactive molecules, including collagen, elastin, laminin, and various growth factors. CCK-8 and scratch assay showed that ADSC-dECM treatment could significantly promote the proliferation and migration of HaCaT, human umbilical vein endothelia cells, and human fibroblasts, respectively. To evaluate the therapeutic effect on wound healing in vivo, we developed a novel ADSC-dECM-CMC patch and transplanted it into a mouse full-thickness skin wound model. And we found that ADSC-dECM-CMC patch treatment significantly accelerated the wound closure with time. Further histology and immunohistochemistry indicated that ADSC-dECM-CMC patch could promote tissue regeneration, as confirmed via enhanced angiogenesis and high cell proliferative activity. Conclusion: In this study, we developed a novel ADSC-dECM-CMC patch containing multiple bioactive molecules and exhibiting good biocompatibility for skin reconstruction and regeneration. This patch provides a new approach for the use of adipose stem cells in skin tissue engineering.

Identification of IGF2 promotes skin wound healing by co-expression analysis.

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

Multifunctional fish-skin collagen-based hydrogel sealant with dual-dynamic-bond cross-linked for rapid hemostasis and accelerated wound healing

Collagen (COL) is the most widespread functional protein. Designing and developing dual-dynamic-bond cross-linked COL adhesive hydrogel sealants with multifunctional is highly advantageous for achieving a superior wound closure effect and hemostasis. In this study, we developed hybrid hydrogels consisting of fish-skin COL, oxidized sodium alginate (OSA), borax and polyvinyl alcohol (PVA) to enhance full-thickness wound healing. The hydrogels were furnished with first-rate self-healing capabilities through the dual-dynamic-bond cross-linking of dynamic Schiff base bonds (COL-OSA) and diol boric acid bonds (OSA-borax) with reversible breakage and re-formation. Moreover, the incorporation of PVA stimulated the formation of hydrogen bonds in the system, bolstering the stability of the hydrogel framework. The prepared hydrogel manifests self-healing, injectability, multifunctional adhesiveness and biodegradability. In vivo assessment of the hemostatic capacity of COSP20 hydrogel was superior to gauze both in the mice liver injury model and mice tail amputation model. In addition, a full-thickness skin wound model in mice revealed that the COSP20 hydrogel facilitated faster wound closure by accelerating reepithelialization, COL deposition and angiogenesis. These findings illustrate the potential of hybrid fish-skin COL-based hydrogels to enhance wound healing and promote rapid tissue repair, and provide new possibilities for the effective utilization of marine fishery resources.

A novel sprayable thermosensitive hydrogel containing a sulfobutylether-β-cyclodextrin/glabridin inclusion complex promotes wound healing

This study concentrated on developing a novel sprayable hydrogel by the combination of a thermosensitive hydrogel (Pluronic F-127, PF-127) and an inclusion complex of glabridin (GLD) and sulfobutylether-β-cyclodextrin (SBE-β-CD). GLD was encapsulated into SBE-β-CD by the freeze-drying method. The successful encapsulation of the inclusion complex was verified by Fourier transform infrared (FT-IR), X-ray diffractometer (XRD), scanning electron microscope (SEM), and nuclear magnetic resonance spectroscopy (NMR). The prepared GLD/SBE-β-CD inclusion complex exhibited 93.24%～96.46% encapsulation efficiency and 11.24%～11.93% loading capacity, and GLD/SBE-β-CD showed excellent biocompatibility on human vascular endothelial cells (HUVECs) and erythrocytes. GLD/SBE-β-CD inclusion complex exerts higher antioxidant and antibacterial activity than GLD alone. The GLD/SBE-β-CD inclusion complex was well dispersed within 20% PF-127 solution to form the PF-127/GLD/SBE-β-CD hydrogel. Introducing the inclusion complex into the PF-127 hydrogel did not influence its loose and porous structure, while PF-127/GLD/SBE-β-CD hydrogel demonstrated controlled GLD release in a sustained manner. The full-thickness skin wound model showed that the PF-127/GLD/SBE-β-CD hydrogel accelerated the healing of traumatic skin defects. In one aspect, the porous and biocompatible structure of the hydrogel provides favorable conditions for skin cell adhesion and proliferation. In another respect, GLD in therapeutic hydrogel markedly promotes the angiogenesis of endothelial cells, and the migration of keratinocytes. It also presents excellent antibacterial properties in wound surface. Taken together, this work established a novel sprayable hydrogel (PF-127/GLD/SBE-β-CD) and proved that it is an effective strategy for traumatic wound healing.

Egg White Peptides Accelerating the Wound Healing Process Through Modulating the PI3K-AKT Pathway: A Joint Analysis of Transcriptomic and Proteomic.

Wound healing is a multiphase process with a complex repair mechanism; trauma-repairing products with safety and high efficiency have a great market demand. Egg white peptides (EWP) have various physiological regulatory functions and have been proven efficient in ameliorating skin damage. However, their underlying regulation mechanism has not been revealed. This study further evaluated the EWP ameliorating mechanism by conducting a full-thickness skin wound model. Results demonstrated that EWP administration significantly inhibited the expression of pro-inflammatory and shortened the inflammatory phase. Besides, EWP can accelerate the secretion of growth factors (PDGF, VEGF, and TGF-β1) in skin tissue, significantly increasing the regeneration of granulation tissue and endothelium in the proliferation phase, thereby promoting wound healing. After 400 mg/kg EWP interventions for 13 days postoperation, the wound healing rate reached 90%. The combination of transcriptomic and proteomic analyses demonstrated the ameliorating efficiency effects of EWP on wound healing. EWP mainly participates in the functional network with the PI3K-AKT signaling pathway as the core to accelerate wound healing. These findings suggest a promising EWP-based strategy for accelerating wound healing.

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.

Wound recovery efficacy of retinol based-micellar formulations in an organotypic skin wound model

Impairment of the skin's structural integrity initially results in acute wounds which can become chronic if timely wound closure is not achieved. Chronic wounds (CWs) affect more than 1% of the global population with increasing cases of this condition due to the ageing population. Current wound management relies on debridement, hyperbaric oxygen, antibiotics, and wound dressings, which lack early intervention and specificity. Herein, antibiotics-free retinol-based micellar formulations (RMF) were made and their wound healing efficacy were investigated in vitro. Five different formulations with retinol contents of 0.3% and 1% against a placebo were topically applied to an organotypic full-thickness skin wound model (FT-SWM, MatTek®) with a 3 mm punch wound, and maintained in an incubator for 6 days. The histological analysis of the FT-SWM was conducted at depths of 60 µm and 80 µm. It was found that all the micellar retinol formulations accelerated wound bed contraction, with 0.3% RMF demonstrating the highest efficacy. At the depths of 60 µm and 80 µm, the 0.3% RMF exhibited inner wound diameter contraction of 58% and 77%, respectively, in comparison to the placebo showing 15% and 8%. The RMF significantly accelerated wound healing and can thus be a potential early intervention for speedy wound recovery. It should be pointed out that these results were obtained based on a small sample size and a large sample size will be explored to further validate the results.

Hydrogel-Functionalized Bandages with Janus Wettability for Efficient Unidirectional Drug Delivery and Wound Care.

Chronic wounds have imposed a severe physical and economic burden on the global healthcare system, which are usually treated by the delivery of drugs or bioactive molecules to the wound bed through wound dressings. In this work, we have demonstrated a hydrogel-functionalized bandage with Janus wettability in a bilayer structure to achieve unidirectional drug delivery and multifunctional wound care. The Janus patterned bandage with porous gradient wetting channels on the upper layer is responsible for the unidirectional transport of the drug from the outside to the wound bed (up to 90% drug transport efficiency) while preventing drug diffusion in unwanted directions (<8%). The hydrogel composed of chitosan quaternary ammonium salt (HACC), poly(vinyl alcohol) (PVA), and poly(acrylic acid) (PAA) at the bottom layer further functionalized such a bandage with biocompatibility, excellent antibacterial properties, and hemostatic ability to promote wound healing. Especially, the hydrogel-functionalized bandage with Janus wettability exhibits excellent mechanical flexibility (∼198% strain), which can comply well with skin deformation (stretching, bending, or twisting) and maintain unidirectional drug delivery behavior without any leakage. The in vivo full-thickness skin wound model confirms that the hydrogel-functionalized bandage can significantly facilitate epithelialization and collagen deposition and improve drug delivery efficiency, thus promoting wound closure and healing (the wound healing ratio was 98.10% at day 15). Such a synergistic strategy of unidirectional drug delivery and multifunctional wound care provides a more efficient, economical, and direct method to promote wound healing, which could be used as a potential high-performance wound dressing for clinical application.

Hydrogel loaded with exosomes from Wharton's Jelly-derived mesenchymal stem cells enhances wound healing in mice.

To explore the effect of hydrogel loaded with exosomes from Wharton's Jelly-derived mesenchymal stem cell (WJMSC) on wound healing. Exosomes were extracted from WJMSC, and the morphology and size of WJMSC-derived exosomes (WEX) were analyzed by transmission electron microscopy and nanoparticle size analyzer, respectively. The surface markers CD9, CD81, and Calnexin of WEX were detected by Western blotting. Exosome-loaded alginate hydrogel (WEX-gel) was prepared; its morphology was studied by scanning electron microscope, and its rheological behavior was examined by a rheometer. The in vitro drug release performance of WEX-gel was investigated by BCA method. RAW264.7 cells were treated with alginate hydrogel, WEX and WEX-gel, respectively; and the expression of CD86 and CD206 in macrophages was detected by flow cytometry. A full-thickness skin wound model was established in mice; the model mice were randomly divided into blank control group, WEX control group and WEX-gel group, and PBS, WEX and WEX-gel were applied to the wound area of mice, respectively. On day 3, the skin tissue of mice was excised, and the antibacterial effect of WEX hydrogel was evaluated by plate counting. On day 15, the mice were euthanized and the percentage of residual wounds was calculated. The histological changes of the skin wound were observed after hematoxylin and eosin (HE) and Masson stainings. The expression of CD86, CD206, CD31 and vascular endothelial growth factor (VEGF) in the skin wound tissue was detected by immunohistochemistry. Exosomes were successfully extracted from WJMSC. WEX-gel presented a regular three-dimensional network structure, good rheology and controlled drug release performance. WEX-gel promoted the polarization of RAW264.7 cells from the M1 phenotype to M2 phenotype in vitro. The residual wound percentage in blank control group, WEX control group and WEX-gel group were (27.5±3.4)%, (15.3±1.2)% and (7.6±1.1)%, respectively (P<0.05). The antibacterial property of WEX-gel is better than that of WEX (P<0.05). The dermis thickness, the number of new hair follicles, and the rate of collagen deposition in the WEX-gel group were significantly higher than those in the other two groups (all P<0.05). The expression of CD206, CD31 and VEGF in skin wound tissue was higher and the expression of CD86 was lower in WEX-gel group than those in other two groups (all P<0.05). WEX-gel can significantly promote wound healing in mice by regulating the polarization of macrophages.

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.

A highly stretchable, adhesive, and antibacterial hydrogel with chitosan and tobramycin as dynamic cross-linkers for treating the infected diabetic wound

Diabetic wounds pose a significant challenge due to their susceptibility to bacterial infection in a high-glucose environment, which impedes the wound healing process. To address this issue, there is a pressing need to develop suitable hydrogels that can promote the regeneration of diabetic wounds in clinical practice. In this study, we designed and fabricated a highly stretchable, adhesive, transparent, and antibacterial hydrogel through a one-pot radical polymerization of N-[Tris (hydroxymethyl) methyl] acrylamide (THMA) and acrylic acid (AA), and with chitosan and the antibiotic tobramycin as the dynamic physical crosslinkers. The copolymer contains a large number of carboxyl and hydroxyl groups, which can form an interpenetrating network structure with chitosan and tobramycin through multiple dynamic non-covalent bonds. This hydrogel exhibited over 1600 % elongation through an energy dissipation mechanism and strong adhesion to various surfaces without any chemical reaction. In vivo, studies conducted on a staphylococcus aureus-infected full-thickness diabetic skin wound model demonstrated that the hydrogel loaded with tobramycin as one of the crosslinkers had a long-lasting antibacterial activity and effectively accelerated wound healing. Therefore, the antibiotic-loaded adhesive hydrogel we proposed holds great promise as a treatment for bacteria-infected diabetic wounds.

The bone mesenchymal stem cell-derived exosomal miR-146a-5p promotes diabetic wound healing in mice via macrophage M1/M2 polarization

A diabetic wound is a refractory disease that afflicts patients globally. MicroRNA-146a-5p (miR-146a-5p) is reported to represent a potential therapeutic target for diabetic wounds. However, microRNA easily degrades in the wound microenvironment. This study extracted bone marrow mesenchymal stem cell (BMSC)-derived exosomes (EXO). Electroporation technology was used to load miR-146a-5p into EXO (labeled as EXO-miR-146a). The endothelial cells (human umbilical vein endothelial cells [HUVECs]) and macrophages were cocultured in transwell chambers in the presence of high glucose. Cell proliferation, migration, and angiogenesis were measured with cell counting kit 8, scratch, and tube forming assays, respectively. Flow cytometry was introduced to validate the biomarker of macrophages and BMSCs. The expression level of macrophage polarization-related proteins and tumor necrosis factor receptor-associated factor 6 (TRAF6) was assessed with western blotting analysis. The full-thickness skin wound model was developed to verify the in vitro results. EXO-miR-146a promoted the proliferation, migration, and angiogenesis of HUVECs in the hyperglycemic state by suppressing the TRAF6 expression in vitro. Additionally, EXO-miR-146a treatment facilitated M2 but inhibited M1 macrophage polarization. Furthermore, EXO-miR-146a enhances reepithelialization, angiogenesis, and M2 macrophage polarization, thereby accelerating diabetic wound healing in vivo. The EXO-miR-146a facilitated M2 macrophage polarization, proliferation, migration, and angiogenesis of HUVECs through TRAF6, thereby ameliorating intractable diabetic wound healing. These results established the basis for using EXO to deliver drugs and revealed mediators for diabetic wound treatment.

A Photocurable Polysaccharide-Based Hydrogel Delivery of Polydeoxyribonucleotide-Loaded Vectors for Wound Treatment.

The wounds caused by war, accidents, and diseases require timely and effective treatment. Polysaccharides, as natural macromolecules, have good biocompatibility and unique functions, and are excellent substrates for constructing new wound dressings. Short-chain chitosan (SCS) has good water solubility and, importantly, retains a large number of active amino groups. We first introduce double bonds to SCS. This chitosan derivative can be entangled with sodium alginate (SA) through electrostatic interaction. The flowing sol can be applied to a wound with an irregular shape. Under the initiation of a photoinitiator, the internal double bonds are broken and cross-linked to form a gel. The prepared hydrogel wound dressing exhibited good antibacterial properties and can provide a microenvironment conducive to wound repair. A polydeoxyribonucleotide (PDRN) has been proven to have encouraging therapeutic effects for wound healing. PDRN can be condensed by branched polyethylenimine (PEI) to form a nucleic acid delivery system, which can be efficiently uptaken by cells. The cooperation of hydrogel and nucleic-acid-based therapy presented good results in a mouse full-thickness skin wound model.