Full-thickness Skin Defects Research Articles

Multifunctional Dual Nano-MOF-Modified Decellularized Small Intestinal Submucosa Membrane Accelerates Healing of Infected Wound.

The treatment of complex or chronic skin wounds caused by burns, trauma, surgery, and genetic disorders has been a worldwide challenge. Small intestinal submucosa (SIS) is a biological material that is widely used in wound healing. How to further expand the wound healing application of SIS, especially in repairing infected wounds, remains a hot research topic for many tissue engineering and biomaterial scholars focusing on skin regeneration. This study uses nanometal-organic frameworks (nano-MOFs), which have not been applied to modify the SIS membrane before, to construct multifunctional dual nano-MOFs @ SIS membrane (dnMOF@SISm). Nano-MOFs are functionalized onto the nanofiber of SIS via in situ self-assembly under mild reaction conditions without any toxic reagent or complex instruments. The dnMOF@SISm can release Co2+, Zn2+, and bioactive factors, participating in the whole stage of the repair of infected wounds. In vitro, it can regulate the biological activities of various functional cells such as fibroblasts, endothelial cells, and macrophages and shows good antibacterial ability. In the infected full-thickness skin defect rat model, dnMOF@SISm can release metal ions and ligands, killing pathogenic bacteria colonized on the wound surface at the first stage, and then trigger and accelerate the skin repair process via angiogenesis, immune regulation, and collagen deposition. Above all, an efficient, nontoxic, mild self-assembly strategy realizes the functionalization of dual nano-MOFs on the nanofiber of SIS to expand its clinical application scenarios, especially in infected wounds.

Rotating cell culture system-induced injectable self-assembled microtissues with epidermal stem cells for full-thickness skin repair.

Epidermal stem cells (EpSCs) are crucial for wound healing and tissue regeneration, and traditional culture methods often lead to their inactivation. It is urgent to increase the yield of high quality EpSCs. In this study, primary EpSCs were isolated and cultured in a serum-free, feeder-free culture system. EpSCs are then expanded in a dynamic 3D environment using a rotating cell culture system (RCCS) with biodegradable porous microcarriers (MC). Over a period of 14 days, the cells self-assembled into microtissues with superior cell proliferation compared to 3D static culture. Immunofluorescence and qPCR analyses consistently showed that the stemness of the 3D microtissues was preserved, especially the COL17A1 associated with anti-aging was highly expressed in RCCS induced microtissues. In vivo experiments demonstrated that the group treated with 3D microtissues loaded with EpSCs showed enhanced early wound healing, and the injectable 3D microtissues were more conducive to maintaining cell viability and differentiation potential. Our study provides valuable insights into the dynamic 3D culture of EpSCs and introduces an injectable therapy using 3D microtissues loaded with EpSCs, which provides a new and effective approach for cell delivery and offering a promising strategy for guiding the regeneration of full-thickness skin defects.

Enhancing wound healing through innovative technologies: microneedle patches and iontophoresis.

Wound healing is a complex process involving multiple stages, including inflammation, proliferation, and remodeling. Effective wound management strategies are essential for accelerating healing and improving outcomes. The CELLADEEP patch, incorporating iontophoresis therapy and microneedle technology, was evaluated for its potential to enhance the wound healing process. This study utilized a full-thickness skin defect model in Sprague-Dawley rats, researchers compared wound healing outcomes between rats treated with the CELLADEEP Patch and those left untreated. Various histological staining techniques were employed to examine and assess the wound healing process, such as H&E, MT and immunofluorescence staining. Furthermore, the anti-inflammatory and proliferative capabilities were further investigated using biochemical assays. Macroscopic and microscopic analyses revealed that the CELLADEEP patch significantly accelerated wound closure, reduced wound width, and increased epidermal thickness and collagen deposition compared to an untreated group. The CELLADEEP patch decreased nitric oxide and reactive oxygen species levels, as well as pro-inflammatory cytokines IL-6 and TNF-α, indicating effective modulation of the inflammatory response. Immunofluorescence staining showed reduced markers of macrophage activity (CD68, F4/80, MCP-1) in the patch group, suggesting a controlled inflammation process. Increased levels of vimentin, α-SMA, VEGF, collagen I, and TGF-β1 were observed, indicating enhanced fibroblast activity, angiogenesis, and extracellular matrix production. The CELLADEEP patch demonstrated potential in promoting effective wound healing by accelerating wound closure, modulating the inflammatory response, and enhancing tissue proliferation and remodeling. The CELLADEEP patch offers a promising non-invasive treatment option for improving wound healing outcomes.

Effect of aspirin on platelet-rich plasma of diabetes mellitus with lower extremity atherosclerosis.

Aim: Platelet-rich plasma (PRP), enriched with multiple growth factors, is a promising adjunctive therapy for diabetic foot ulcers (DFUs). As a classic anti-platelet drug for diabetic patients, the effects of aspirin on the content of growth factors in PRP remains unclear.Methods: Our study enrolled diabetic patients who were currently taking or not taking aspirin as the research subjects, with healthy volunteers as the control. PRP from these individuals was activated with glucose calcium and thrombin. Growth factors levels in PRP activated supernatant (PRP-AS) and wound healing ability of platelet gel (PG) in the full-thickness skin defect diabetic mouse model were compared.Results: We found the level of growth factors in PRP-AS derived from two groups of diabetic patients were not statistically different, whereas both lower than that from healthy volunteers. Similarly, we found better wound healing ability of PG from healthy volunteers than those from diabetic patients, but no difference between the two groups of diabetic patients in the mouse model.Discussion: Aspirin does not interfere with autologous PRP therapy when using calcium gluconate and thrombin as agonists. However considering the content of growth factors, PRP from healthy volunteers is a preferable option for promoting DFU repair.

Construction and Performance Study of an Injectable Dual-Network Hydrogel Dressing with Inherent Drainage Function.

With the widespread utilization of moist wound dressings, the extended healing time and increased risk of wound infection caused by excessively moist environments have garnered significant attention. The development of hydrogel dressings that can effectively control the wound moisture level and promote healing is very important. Inspired by the pore-opening perspiration effect of the skin, this study constructed an injectable dual-network hydrogel, CMCS-OSA/AG/MXene, by the composition of a dynamic covalent network of carboxymethyl chitosan and oxidized sodium alginate based on the Schiff base and hydrogen bond network of the thermosensitive low-melting-point agar with the advantage of the upper critical solution temperature (UCST) effect. Under near-infrared (NIR) light stimulation, the CMCS-OSA/AG/MXene hydrogel shows characteristics conducive to rapid removal of wound exudate while maintaining an appropriate moist environment for the wound and excellent antibacterial effects with its photothermal responses. The excellent conductivity of the hydrogel can also promote cell proliferation under external electrical stimulation (ES). Further validation through animal experiments on a full-thickness skin defect model demonstrates the excellent capability of CMCS-OSA/AG/MXene in accelerating wound healing. This work provides an innovative approach to the development of injectable hydrogel dressing materials with inherent drainage functionality and shows a new avenue to wound moisture control and wound healing promotion.

Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing

Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds.Graphical

Combination therapy of placenta-derived mesenchymal stem cells and artificial dermal scaffold promotes full-thickness skin defects vascularization in rat animal model

PurposeRecently, placenta-derived mesenchymal stem cells (PMSCs) have garnered considerable attention in tissue repair and regeneration. The present study was conducted to evaluate the effect of PMSCs on artificial dermal scaffold (ADS) angiogenesis and their combination therapy on wound closure. Material and methodsHerein, the growth and survival of PMSCs in ADS were explored. CCK8, scratch wound, and tubule formation assays were employed to investigate the effects of ADS conditioned medium (CM) and ADS-PMSCs CM on human umbilical vein endothelial cells (HUVECs). The effect of ADS-PMSCs on full-thickness skin defects healing was evaluated based on a rat model. Wound healing progresses was meticulously investigated through hematoxylin and eosin (HE), Masson’s trichrome, and immunohistochemical staining analyses. ResultsIn vitro cell culture results demonstrated the proliferation of PMSCs in ADS. The ADS-PMSCs CM notably stimulated the proliferation, migration, and tube formation of HUVECs compared to the ADS CM group. In the rat full-thickness skin defect model, the ADS-PMSCs treatment significantly accelerated the vascularization area of ADS after 2 weeks. Besides, HE and Masson’s trichrome staining results indicated that ADS-PMSCs treatment significantly enhanced fibroblast proliferation and collagen fiber 2 weeks after surgical procedure. Compared to the ADS group, collagen fiber arrangement was thicker in the ADS-PMSCs group. Immunohistochemical staining reinforced this finding, illustrating a substantial increase in CD31 expression within the ADS-PMSCs group. ConclusionsThe results suggest that the combination of ADS with PMSCs accelerates ADS vascularization by fostering granulation tissue development and boosting the formation of new blood vessels.

Facilitation of diabetic wound healing by far upstream element binding protein 1 through augmentation of dermal fibroblast activity.

Diabetes mellitus (DM) often leads to wound healing complications, partly attributed to the accumulation of advanced glycosylation end products (AGEs) that impair fibroblast function. Far Upstream Element Binding Protein 1 (FUBP1) regulates cell proliferation, migration, and collagen synthesis. However, the impact of FUBP1 on diabetic wound healing remains unknown. This study is designed to explore the function and mechanisms of FUBP1 in diabetic wound healing. Eighteen Sprague-Dawley rats (weighing 220-240g) were randomly assigned to three groups (n = 6): a control group (NC) of healthy rats, a model group (DM) of untreated diabetic rats, and a treatment group (DM + FUBP1) of diabetic rats accepting FUBP1 treatment. A 10mm diameter circular full-thickness skin defect was created on the back of each rat. On days 1 and 7, rats in the treatment group received local injections of 5µg FUBP1 protein at the wound site, whereas the control group and model group were administered saline. Wound healing was documented on days 0, 3, 7, 10, and 14, with tissue samples from the wound areas collected on day 14 for histological analysis, including H&E staining, Masson's trichrome staining, and immunohistochemistry. Western blot analysis was utilized to assess the expression of GSK-3β, Wnt3a, and β-catenin. In vitro, the effects of various concentrations of AGEs on cell viability and FUBP1 expression were examined in human dermal fibroblasts (HDF). Cells were genetically modified to overexpress FUBP1 using lentiviral vectors and were cultured for 48h in media with or without AGEs. The impacts on fibroblast proliferation, migration, and Wnt/β-catenin signaling were evaluated using CCK-8, scratch assays, and Western blot analysis. Animal investigation revealed that from day 7 onwards, the wound healing rate of the treatment group was higher than that of the model group but lower than the control group. On day 14, the wound healing rates were as follows: control group (0.97 ± 0.01), model group (0.84 ± 0.03), and treatment group (0.93 ± 0.01). These differences were statistically significant. Histological analysis indicates that FUBP1 promotes granulation tissue formation, re-epithelialization, and collagen deposition in treatment group. Additionally, FUBP1 protein expression decreased in dermal fibroblasts when exposed to AGEs. Overexpression of FUBP1 significantly enhanced fibroblast proliferation and migration, activating the Wnt/β-catenin pathway and mitigating the inhibitory effects of AGEs. Our results suggest that FUBP1 can be a promising therapeutic target for diabetic wound healing, potentially counteracting the detrimental effects of AGEs on dermal fibroblasts through the Wnt/β-catenin pathway.

Ozonated Aloe Vera: A Novel Topical Agent for Improved Wound Healing and Reduced Scar Formation on TGF-β Modulation Invivo Study

Background: Chronic wounds and impaired wound healing represent a significant healthcare burden. Aloe vera has been recognized for its therapeutic potential in wound healing, and the combination with ozone, and ozonated aloe vera, may offer synergistic effects. This study investigated the effects of ozonated aloe vera oil on wound healing and scar formation, focusing on TGF-β modulation in a rat model. Methods: Full-thickness skin defects were created on 50 Sprague Dawley rats, which were randomly divided into five groups: (1) control (untreated), (2) aloe vera oil, (3) ozonated aloe vera oil (600 mg/ml ozone), (4) ozonated aloe vera oil (1200 mg/ml ozone), and (5) ozonated aloe vera oil (1800 mg/ml ozone). Wound healing was assessed macroscopically by measuring wound area reduction and microscopically by evaluating TGF-β expression through immunohistochemical staining on days 3, 7, and 14. Results: Ozonated aloe vera oil significantly accelerated wound healing compared to the control and aloe vera oil alone groups (p < 0.05). The highest ozone concentration (1800 mg/ml) showed the most rapid wound closure and the lowest TGF-β expression on day 14 (p < 0.05). Histological analysis revealed enhanced collagen organization and reduced inflammatory cell infiltration in ozonated aloe vera oil treated wounds. Conclusion: Ozonated aloe vera oil effectively promotes wound healing and reduces scar formation in a rat model. The modulation of TGF-β signaling plays a crucial role in these effects. Ozonated aloe vera oil holds promise as a novel topical agent for improved wound management.

Protocatechuic acid grafted chitosan/oxidized glucomannan hydrogel with antimicrobial and anti-inflammatory effects for enhancing wound repair

Oxidative stress, inflammation, and bacterial infection are critical barriers to wound healing. In this work, a composite wound dressing was designed to promote wound healing and reduce complications. A hydrogel with antibacterial, anti-inflammatory, and antioxidant properties was prepared by crosslinking chitosan (CS) and oxidized konjac glucomannan with Mg2+. We named the prepared hydrogel CPO/Mg2+. The proposed hydrogel demonstrated a significant capacity for promoting wound healing. Experimental results indicate that the CPO/Mg2+ composite hydrogel exhibits a bacteriostatic rate of over 95 % against S. aureus and P. aeruginosa. Furthermore, CPO/Mg2+ reduced oxidative damage to L929 cells in an H2O2-induced ROS microenvironment and promoted the polarization of macrophage M2. In vivo full-thickness skin defect experiments revealed that the CPO/Mg2+ composite hydrogel enhances collagen deposition and angiogenesis, achieving a closure rate of over 95 % for infected wounds within 14 days. This novel composite hydrogel offers an effective strategy for the repair of infected wounds.

Influence of polylactide wound dressings with tannic acid on serum concentration of markers of angiogenesis, endothelial cell alteration and activation in white rats during healing of experimental full-thickness skin defect

Influence of polylactide wound dressings with tannic acid on serum concentration of markers of angiogenesis, endothelial cell alteration and activation in white rats during healing of experimental full-thickness skin defect

3D bioprinting of fish skin-based gelatin methacryloyl (GelMA) bio-ink for use as a potential skin substitute.

Gelatin methacryloyl (GelMA), typically derived from mammalian sources, has recently emerged as an ideal bio-ink for three-dimensional (3D) bioprinting. Herein, we developed a fish skin-based GelMA bio-ink for the fabrication of a 3D GelMA skin substitute with a 3D bioprinter. Several concentrations of methacrylic acid anhydride were used to fabricate GelMA, in which their physical-mechanical properties were assessed. This fish skin-based GelMA bio-ink was loaded with human adipose tissue-derived mesenchymal stromal cells (ASCs) and human platelet lysate (HPL) and then printed to obtain 3D ASCs + HPL-loaded GelMA scaffolds. Cell viability test and a preliminary investigation of its effectiveness in promoting wound closure were evaluated in a critical-sized full thickness skin defect in a rat model. The cell viability results showed that the number of ASCs increased significantly within the 3D GelMA hydrogel scaffold, indicating its biocompatibility property. In vivo results demonstrated that ASCs + HPL-loaded GelMA scaffolds could delay wound contraction, markedly enhanced collagen deposition, and promoted the formation of new blood vessels, especially at the wound edge, compared to the untreated group. Therefore, this newly fish skin-based GelMA bio-ink developed in this study has the potential to be utilized for the printing of 3D GelMA skin substitutes.

Nanofat Improves Vascularization and Tissue Integration of Dermal Substitutes without Affecting Their Biocompatibility.

Dermal substitutes require sufficient tissue integration and vascularization to be successfully covered with split-thickness skin grafts. To rapidly achieve this, we provide the proof of principle for a novel vascularization strategy with high translational potential. Nanofat was generated from subcutaneous adipose tissue of green fluorescence protein (GFP)+ C57BL/6J donor mice and seeded onto small samples (4 mm in diameter) of the clinically approved dermal substitute Integra®. These samples and non-seeded controls were then implanted into full-thickness skin defects in the dorsal skinfold chamber of C57BL/6J wild-type mice and analyzed by intravital fluorescence microscopy, histology and immunohistochemistry over a 14-day period. Nanofat-seeded dermal substitutes exhibited an accelerated vascularization, as indicated by a significantly higher functional microvessel density on days 10 and 14 when compared to controls. This was primarily caused by the reassembly of GFP+ microvascular fragments inside the nanofat into microvascular networks. The improved vascularization promoted integration of the implants into the surrounding host tissue, which finally exhibited an increased formation of a collagen-rich granulation tissue. There were no marked differences in the inflammatory host tissue reaction to nanofat-seeded and control implants. These findings demonstrate that nanofat significantly improves the in vivo performance of dermal substitutes without affecting their biocompatibility.

Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats.

Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the PHGPx, SLC7A11 and SLC40A1 genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. PHPGx and SLC7A11 genes in kidney and liver tissue were statistically significant (P < 0.05) except for the SLC40A1 gene (P > 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.

Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats

BackgroundWound healing is a complex procedure that requires the coordination of several factors, so this study aimed to assess the zinc oxide nanoparticles’ regenerated effect and stem cell exosomes on full-thickness wounds in rats. MethodsSeventy-two Wistar male rats were subjected to a full-thickness skin defect (20 mm2) on the dorsal surface of each rat between two shoulder joints. The rats were randomized into four groups (18/group) according to wound treatments. The wounds were irrigated with normal saline (Control group), or the wound's edges were subcutaneously injected daily with 0.3 ml of exosome (Exo-group), or 1 ml of zinc oxide nanoparticles (ZnO2-NPs group), or 0.3 ml of exosome in combined with 1 ml of zinc oxide nanoparticles (Exo/ZnO2-NPs group). On the 7th, 14th, and 21st days post-wounding, the weight of the rats, the wound healing breaking strength, the wound size, and the contraction percent were evaluated. Six rats in each group were euthanized at each time point for histopathological, immunohistochemical examination of collagen, the levels of alpha-smooth muscle actin (α-SMA), and epidermal growth factor receptor (EGFR). additionally, the gene expression analysis of the relative renal nuclear factor erythroid 2-related factor2 (Nrf2 mRNA), Transforming growth factor beta-1 (TGFβ1), fibroblast growth factor-7 (FGF7), Transforming growth factor beta-1 (TGFβ1), Lysyl oxidase (LOX), and Vascular endothelial growth factor (VEGF) were applied. ResultsThe Exo-group exhibited a significant decrease in wound size and a significant increase in wound contraction compared with other groups. Histopathologically evaluation during the three intervals revealed that the Exo-group had the highest collagen deposition area with a significant reduction of the granulation tissue. Moreover, upregulated gene expression profiles of the growth factors genes at all time points post-wounding. DiscussionThe exosomes-treated group revealed superior wound healing and contraction, with minimal inflammatory signs, higher angiogenesis, and myofibroblasts, and associated with higher growth factor expression genes compared to the other groups. ConclusionsExosome-based therapy demonstrates potential as a treatment method to promote and accelerate wound healing by modulating angiogenesis, re-epithelialization, collagen deposition, and gene expression profiles.

A three-dimensional printable conductive composite dressing for accelerating wound healing under electrical stimulation

In this study, a bioink based on poly(vinyl alcohol) (PVA) and κ-carrageenan network was prepared using conductive polymer (PEDOT:PSS) as conducting medium, and (+)-Catechin-loaded mesoporous ZnO (CmZnO) as antibacterial and anti-inflammatory active medium. 3D conductive composite dressing was further fabricated by an extrusion 3D printing technology. Our results showed that the as-obtained composite dressing had suitable conductivity, efficient blood clotting capacity, and good adhesiveness. It also showed that the as-fabricated conductive composite had 92.9 % and 95.6 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. Furthermore, the conductive dressing with an optimal electrical stimulation (ES) parameter showed in vivo blood clotting capacity, and it enhanced in vivo wound healing process in a full-thickness skin defect model than commercial dressings by upregulating the gene expression of growth factors including CD-31 and downregulating inflammatory factor expression of IL-6.

3D Bilayered Hydrogel and Nanofiber Multifunctional Sponge Dressing: An Efficacious Healing Agent for Chronic Wound Healing.

Chronic wound management using biomaterial-based dressings has significantly impacted the standard and efficiency of wound healing. However, various available wound healing aids are ineffective in treating deep open injuries and chronic wounds such as diabetic wounds. Herein, we developed a 3D bilayered multifunctional sponge, which addresses the structural and functional issues faced by biomaterial dressings in treating deep and chronic wounds. The 3D bilayered sponge consists of a hydrogel base functionalized with wound healing peptide (Tylotoin)-carrying nanoparticles and topped with a nanofiber layer functionalized with an antimicrobial peptide (LLKKK18). The 3D bilayered sponge, with its highly porous, elastic, and enhanced fluid absorption ability, makes it a suitable wound treatment aid. The developed multifunctional 3D sponge shows antibacterial action and promotes a microenvironment similar to the extracellular matrix (ECM) in regulating dermal cell survival and migration. Study in a full-thickness skin defect diabetic mouse model has shown that the developed 3D bilayered sponge accelerated wound closure and promoted functional skin regeneration through reduced inflammation, faster granulation tissue formation, re-epithelialization, neovascularization, and skin appendage restoration, which make the developed 3D bilayered multifunctional sponge an efficient and advanced chronic wound management aid with potential for future clinical application.

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.

Hyaluronic Acid/Gelatin-Based Multifunctional Bioadhesive Hydrogel Loaded with a Broad-Spectrum Bacteriocin for Enhancing Diabetic Wound Healing.

The development of multifunctional wound adhesives is critical in clinical settings due to the scarcity of dressings with effective adhesive properties while protecting against infection by drug-resistant bacteria. Polysaccharide and gelatin-based hydrogels, known for their biocompatibility and bioactivity, assist in wound healing. This study introduces a multifunctional bioadhesive hydrogel developed through dynamic covalent bonding and light-triggered covalent bonding, comprising oxidized hyaluronic acid, methacrylated gelatin, and the bacteriocin recently discovered by our lab, named jileicin (JC). The adhesion strength of the hydrogel, measured at 180 kPa, was 4.35 times higher than that of the fibrin glue. Furthermore, the hydrogel demonstrated robust platelet adhesion, procoagulant activity, and outstanding hemostatic properties in a mouse liver injury model. Incorporating JC significantly enhanced the phagocytosis and bactericidal capabilities of the macrophages. This immunomodulatory function on host cells, coupled with its potent bacterial membrane-disrupting ability, makes JC an effective killer against methicillin-resistant Staphylococcus aureus. In wound repair experiments on diabetic mice with infected full-thickness skin defects, the hydrogel treatment group showed a notable reduction in bacterial load, accelerated M2-type macrophage polarization, diminished inflammation, and hastened wound healing. Owing to its outstanding biocompatibility, antibacterial activity, and controlled adhesion, this hydrogel presents a promising therapeutic option for treating infected skin wounds.

Highly biocompatible, antioxidant and antibacterial gelatin methacrylate/alginate - Tannin hydrogels for wound healing

Gelatin (Gel) hydrogels are widely utilized in various aspects of tissue engineering, such as wound repair, due to their abundance and biocompatibility. However, their low strength and limited functionality have constrained their development and scope of application. Tannic acid (TA), a naturally occurring polyphenol found in plants and fruits, has recently garnered interest as a crosslinking, anti-inflammatory, and antioxidant agent. In this study, we fabricated novel multifunctional gelatin methacrylate/alginate-tannin (GelMA/Alg-TA) hydrogels using chemical and physical crosslinking strategies with gelatin methacrylate (GelMA), alginate (Alg), and TA as the base materials. The GelMA/Alg-TA hydrogels maintained a stable three-dimensional porous structure with appropriate water content and exhibited excellent biocompatibility. Additionally, these hydrogels demonstrated significant antioxidant and antibacterial properties and substantially promoted wound healing in a mouse model of full-thickness skin defects by modulating inflammatory responses and enhancing granulation formation. Therefore, our study offers valuable insights into the design principles of novel multifunctional GelMA/Alg-TA hydrogels, highlighting their exceptional biocompatibility, antioxidant, and antibacterial properties. GelMA/Alg-TA hydrogels are promising candidates for wound healing applications.