Full-thickness Wound Model Research Articles

Preparation and properties of N-glycosylated chitosan/polyvinyl alcohol hydrogels for use in wound dressings.

Chitosan and its derivatives show potent biocompatibility, biodegradability, antimicrobial activity, hemostatic effects, and wound healing properties. Their application in wound dressings has garnered substantial research interest. In this work, we prepared a drug-loaded hydrogel by mixing N-glycosylated chitosan with polyvinyl alcohol (PVA), followed by loading of ofloxacin. A 2:1 volume ratio of chitosan to PVA was found to be optimal based on swelling and water evaporation rates. The slow-drug-release performance of the blended hydrogel was best when the ofloxacin loading was 5.0%. The ofloxacin-loaded hydrogel shows excellent antimicrobial properties in vitro and wound healing ability in an in vivo rabbit full-thickness excision wound model. The chitosan/PVA blended hydrogel has great potential for use in wound dressings and sustained drug release.

M2 Macrophage-Derived Concentrated Conditioned Media Significantly Improves Skin Wound Healing.

Macrophages, with many different phenotypes play a major role during wound healing process, secreting the cytokines crucial to angiogenesis, cell recruitment and ECM remodeling. Therefore, macrophage-derived cytokines may be attractive therapeutic resource for wound healing. To obtain a conditioned media (CM) from macrophages, human monocyte THP-1 cells were seeded on TCP or human fibroblast-derived matrix (hFDM) and they were differentiated into M1 or M2 phenotype using distinct protocols. A combination of different substrates and macrophage phenotypes produced M1- and M2-CM or M1-hFDM- and M2-hFDM-CM, respectively. Proteome microarray determines the cytokine contents in those CMs. CMs-treated human dermal fibroblast (hDFB) was analyzed using collagen synthesis and wound scratch assay. Concentrated form of the CM (CCM), obtained by high-speed centrifugation, was administered to a murine full-thickness wound model using alginate patch, where alginate patch was incubated in the M2-CCM overnight at 4°C before transplantation. On 14day post-treatment, examination was carried out through H&E and Herovici staining. Keratinocyte and M2 macrophages were also evaluated via immunofluorescence staining. Cytokine analysis of CMs found CCL1, CCL5, and G-CSF, where CCL5 is more dominant. We found increased collagen synthesis and faster wound closure in hDFB treated with M2-CM. Full-thickness wounds treated by M2-hFDM-CCM containing alginate patch showed early wound closure, larger blood vessels, increased mature collagen deposition, enhanced keratinocyte maturation and more M2-macrophage population. Our study demonstrated therapeutic potential of the CM derived from M2 macrophages, where the cytokines in the CM may have played an active role for enhanced wound healing.

Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia.

Cell-derived matrix (CDM) has proven its therapeutic potential and been utilized as a promising resource in tissue regeneration. In this study, we prepared a human fibroblast-derived matrix (FDM) by decellularization of in vitro cultured cells and transformed the FDM into a nano-sized suspended formulation (sFDM) using ultrasonication. The sFDM was then homogeneously mixed with Pluronic F127 and hyaluronic acid (HA), to effectively administer sFDM into target sites. Both sFDM and sFDM containing hydrogel (PH/sFDM) were characterized via immunofluorescence, sol–gel transition, rheological analysis, and biochemical factors array. We found that PH/sFDM hydrogel has biocompatible, mechanically stable, injectable properties and can be easily administered into the external and internal target regions. sFDM itself holds diverse bioactive molecules. Interestingly, sFDM-containing serum-free media helped maintain the metabolic activity of endothelial cells significantly better than those in serum-free condition. PH/sFDM also promoted vascular endothelial growth factor (VEGF) secretion from monocytes in vitro. Moreover, when we evaluated therapeutic effects of PH/sFDM via the murine full-thickness skin wound model, regenerative potential of PH/sFDM was supported by epidermal thickness, significantly more neovessel formation, and enhanced mature collagen deposition. The hindlimb ischemia model also found some therapeutic improvements, as assessed by accelerated blood reperfusion and substantially diminished necrosis and fibrosis in the gastrocnemius and tibialis muscles. Together, based on sFDM holding a strong therapeutic potential, our engineered hydrogel (PH/sFDM) should be a promising candidate in tissue engineering and regenerative medicine.

Studying the in vivo application of a liquid dermal scaffold in promoting wound healing in a mouse model.

Lack of matrix deposition is one of the main factors that complicates the healing process of wounds. The aim of this study was to test the efficacy and safety of a liquid dermal scaffold, referred to as MeshFill (MF) that can fill the complex network of tunnels and cavities which are usually found in chronic wounds and hence improve the healing process. We evaluated in vitro and in vivo properties of a novel liquid dermal scaffold in a delayed murine full-thickness wound model. We also compared this scaffold with two commercially available granular collagen-based products (GCBP). Liquid dermal scaffold accelerated wound closure significantly compared with no-treated control and collagen-based injectable composites in a delayed splinted wound model. When we compared cellular composition and count between MF, no treatment and GCBP at the histology level, it was found that MF was the most analogous and consistent with the normal anatomy of the skin. These findings were matched with the clinical outcome observation. The flowable in situ forming scaffold is liquid at cold temperature and gels after application to the wound site. Therefore, it would conform to the topography of the wound when liquid and provides adequate tensile strength when solidified. This patient-ready gelling dermal scaffold also contains the nutritional ingredients and therefore supports cell growth. Applying an injectable liquid scaffold that can fill wound gaps and generate a matrix to promote keratinocytes and fibroblasts migration, can result in improvement of the healing process of complex wounds.

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.

Injectable hydrogel for postoperative synergistic photothermal-chemodynamic tumor and anti-infection therapy

Tumor surgery is usually accompanied by neoplasm residual, tissue defects, and multi-drug resistant bacterial infection, causing high tumor recurrence, low survival rate, and chronic wounds. Herein, a light-activated injectable hydrogel based on bioactive nanocomposite system is developed by incorporating Ag2S nanodots conjugated Fe-doped bioactive glass nanoparticles (BGN-Fe-Ag2S) into biodegradable PEGDA and AIPH solution for inhibiting tumor growth, treating bacterial infection, and promoting wound healing. Under laser irradiation, the photothermal effect mediated by Ag2S nanodots would trigger the decomposition of AIPH, generating alkyl radicals to initiate the gelation of PEGDA. The in-situ gelatinized hydrogel, with outstanding photothermal effect and chemodynamic effect derived from the doped Fe in BGN-Fe-Ag2S, can not only eliminate multidrug-resistant bacteria but also efficiently ablated tumor during treatment. Moreover, the hydrogel significantly accelerated wound healing with more skin appendages in the full-thickness cutaneous wounds model because of the hydrolysis of bioactive glass. These results manifest that this multifunctional hydrogel is a suitable biomaterial to inhibit tumor proliferation and overcome tissue bacterial infection after surgical removal of tumors.

One-Step Synthesis of Multifunctional Chitosan Hydrogel for Full-Thickness Wound Closure and Healing.

Multifunctional hydrogel as a sealant or wound dressing with high adhesiveness and excellent antibacterial activity is highly desirable in clinical applications. In this contribution, one-step synthetic hydrogel based on quaternized chitosan (QCS), tannic acid (TA), and ferric iron (Fe(III)) is developed for skin incision closure and Staphylococcus aureus (S. aureus)-infected wound healing. In this hydrogel system, the ionic bonds and hydrogen bonds between QCS and TA form the main backbone of hydrogel, the metal coordination bonds between TA and Fe(III) (catechol-Fe) endow hydrogel with excellent adhesiveness and (near-infrared light) NIR-responsive photothermal property, and these multiple dynamic physical crosslinks enable QCS/TA/Fe hydrogel with flexible self-healing ability and injectability. Moreover, QCS/TA/Fe hydrogel possesses superior antioxidant, anti-inflammatory, hemostasis, and biocompatibility. Also, it is safe for vital organs. The data from the mouse skin incision model and infected full-thickness skin wound model presented the high wound closure effectiveness and acceleration of the wound healing process by this multifunctional hydrogel, highlighting its great potential in wound management.

Accelerating skin barrier repair using novel bioactive magnesium-doped nanofibers of non-mulberry silk fibroin during wound healing

Novel magnesium doped non-mulberry silk fibroin nanofibers with ability to enhance skin barrier function were successfully fabricated using electrospinning technique for wound healing applications. Magnesium nanoparticles incorporated in the electrospun nanofibers releases Mg2+ ions at the site of implementation. The effect of Mg2+ is of considerable concern in wound healing due to its skin barrier repair ability and its role in blood coagulation. The physicochemical characterization of the scaffold was investigated by determining the morphology and secondary structure confirmation. The effects of Mg2+ ions in silk fibroin microenvironment have been evaluated using SEM, XRD, and FTIR to confirm the incorporation of magnesium in the film. The aim of this study is to see the effect of doped Mg on the structural, physical, and biological properties of non-mulberry silk fibroin (NSF) film. The magnesium doped nanofibrous film exhibited enhanced mechanical property, satisfactory blood clotting ability, and good in vitro degradability. This silk fibroin-based film mimicking extracellular matrix for skin regeneration were constructed using electrospinning technique. The wound healing efficiency of prepared nanofibers were evaluated in full-thickness wound models of rat. The Mg doped silk fibroin film exhibited faster wound healing activity (14 days) among all experimental group. The study indicates the potential of magnesium-doped silk /PVA film as skin substitute film.

VEGF loaded porcine decellularized adipose tissue derived hydrogel could enhance angiogenesis in vitro and in vivo

Decellularized adipose tissue (DAT) has been widely applied in soft tissue regeneration, however, DAT may play a promising role in accelerating wound healing because of suitable physical characteristics and biological properties. In this research, we fabricated the DAT hydrogel and the VEGF loaded heparinized-DAT hydrogel (VEGF hydrogel) and evaluated their efficiency in full-thickness skin wound model. We designed one method to encapsulate VEGF to hep-DAT hydrogel in order to control VEGF release rate. Result showed that the VEGF release could last up to 3 day, and 1 ml hep-DAT hydrogel (5 mg/ml) could bind up to (64.521 ± 11.550) ng VEGF which was 4.2 times to that of DAT hydrogels. Moreover, the VEGF released in 3 days still preserved biological activities that the released VEGF could enhance tube formation of HUVECs in vitro. Otherwise, the VEGF hydrogel could significantly accelerate wound healing compared with DAT hydrogel and VEGF injection, collagen deposition and newly formed vessels in the VEGF hydrogel groups were also higher than those of other groups. We believed that the VEGF hydrogel could be one attractive biomaterial for potential clinical applications.

The Effect of Topically Applied Boric Acid on Ephrin-Eph Pathway in Wound Treatment: An Experimental Study.

Background: Wound healing has a vital importance for the organism and various agents are used to accelerate wound healing. Although the effect of boron on wound healing is known, its mechanisms are not completely clear yet. In this study, the effect of boron in the Ephrin /Eph pathway will be evaluated. Methods: Forty adult female rats were used in the study. A full-thickness excisional wound model was created in all groups divided as Control, Fito, Boron and Plu groups. After the applications performed twice a day and lasting 7 days, skin tissues obtained and evaluated histopathological (inflammatory cell infiltration, oedema, and fibroblast proliferation density) and immunohistochemical (TNF-α, EphrinA1, EphrinB1, EphrinB2 and EphB4). Results: Inflammatory cell infiltration score was found to be higher in the Fito group compared to Boron group (p = .018). Fibroblast proliferation density was higher in Plu group than Boron group (p = .012). While TNF-α was lower in boron group than Plu (p = .027) and Fito (p = .016) groups, EphrinA1 was higher in Boron group than Plu group (p = .005). EphrinB1 expression was higher in Boron group compared to Plu (p = .015) and Fito (p = .015) groups, and the same difference was also observed in EphrinB2 (p values .000). Similarly, EphB4 immunoreactivity was higher in the Boron group compared to Plu (p = .000) and Fito (p = .002). Conclusion: One of the mechanisms of action of boron in wound healing is to increase EphrinB1, EphrinB2 and EphB4. Low TNF-α and histopathological findings indicate that boron limits extensive wound healing.

Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats.

Diabetic chronic wound, which is one of the diabetic complications caused by hyperglycemia, characterized by prolonged inflammation has become one of the most serious challenges in the clinic. Hyperglycemia during diabetes not only causes prolonged inflammation and delayed wound healing but also modulates the activation of nuclear factor-kappa B (NF-κB) and the expression of matrix metalloproteinases (MMPs). Although metformin is the oldest oral antihyperglycemic drug commonly used for treating type 2 diabetes, few studies have explored the molecular mechanism of its topical effect on wound healing. Therefore, we aimed to investigate the molecular effects of topical metformin application on delayed wound healing, which's common in diabetes. In this context, we created a full-thickness excisional wound model in Wistar albino rats and, investigated NF-κB p65 DNA-binding activity and expression levels of RELA (p65), MMP2 and MMP9 in wound samples taken on days 0, 3, 7, and 14 from diabetic/non-diabetic rats treated with metformin and saline. As a result of our study, we showed that topically applied metformin accelerates wound healing by suppressing NF-κB p65 activity and diminishing the expression of MMP2 and MMP9. Diabetic wounds treated with metformin healed even faster than those in the control group that mimicked standard wound healing.

In situ gel implant for postsurgical wound management and extended chemoimmunotherapy against breast cancer recurrence

Postsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment evoked by surgical wounds. Toll-like receptor 4 (TLR4) signaling contributes to NF-κB activation thus secreting various inflammatory cytokines. Herein, we developed an in situ photo-crosslinked hydrogel (D/T gel) concurrently loaded with doxorubicin (DOX) and a TLR4 antagonist, resatorvid (TAK-242). Its therapeutic effect against breast cancer postsurgical relapse was accomplished through remodeling the proinflammatory tumor microenvironment. The obtained gel network exhibited ideal biodegradability and biocompatibility, which motivated dermal wound healing in the full thickness wound model in mice. Despite the initial burst release of DOX, D/T gels exhibited extended-release of both DOX and TAK-242 for up to 21 days in vitro. TAK-242 was demonstrated to inhibit the lipopolysaccharide-induced NF-κB activation and downregulate TLR4 levels in both RAW264.7 and 4T1 cells. In a 4T1-Luc tumor postsurgical recurrence model, D/T gel significantly suppressed recurrent tumor growth by elevating the concentrations of DOX and TAK-242 at the tumor sites and remodeling the TLR4 activation-induced proinflammatory microenvironment. Overall, the D/T gel platform technology is proven to deliver therapeutics directly to the surgical wound bed, attenuating the dual inflammatory responses induced by DOX and surgical wounding thus greatly potentiating its efficacy in preventing postsurgical tumor recurrence. Statement of significancePostsurgical recurrence of breast cancer is closely related to the inflammatory tumor microenvironment (TME) evoked by surgical wounds. Although chemotherapeutics lead to extensive residual tumor cell necrosis, multiple inflammatory cytokines are secreted simultaneously, which are conducive to tumor recurrence. In this work, a TLR4 antagonist, TAK-242, was combined with DOX to reverse the dual inflammatory TME induced by surgical wounding and chemotherapy. To elevate the concentration of therapeutics at the tumor site, a photocrosslinked hydrogel (D/T gel) implant coloaded with TAK-242 and DOX was developed and applied on the postsurgical bed. Consequently, D/T gel attenuated the dual inflammatory responses and greatly potentiated its efficacy in preventing postsurgical tumor recurrence.

A novel multifunctional bilayer scaffold based on chitosan nanofiber/alginate-gelatin methacrylate hydrogel for full-thickness wound healing

Due to their lack of multifunctionality, the majority of traditional wound dressings do not support all the clinical requirements. Bilayer wound dressings with multifunctional properties can be attractive for effective skin regeneration. In the present study, we designed a multifunctional bilayer scaffold containing Chitosan-Polycaprolactone (PC) nanofiber and tannic acid (TA) reinforced methacrylate gelatin (GM)/alginate (Al) hydrogel (GM/Al/TA). PC nanofibers were coated with GM/Al/TA hydrogel to obtain a bilayer nanocomposite scaffold (Bi-TA). The GM/Al/TA hydrogel layer of Bi-TA showed antibacterial, free radical scavenging, and biocompatibility properties. Also, PC nanofiber acted as a barrier for preventing bacterial invasion and moisture loss of the hydrogel layer. The wound healing performance of the Bi-TA scaffold was investigated via a full-thickness wound model. In addition, the histopathological and immunohistochemical (IHC) stainings of transforming growth factor-β1(TGF-β1) and tumor necrosis factor-α (TNF-α) were assessed. The results indicated an enhanced wound closure rate, effective collagen deposition, quick re-epithelialization, more skin appendages, and replacement of defect area with normal skin tissue by Bi-TA scaffold compared to other groups. Additionally, the regulation of TGF-β1 and TNF-α was observed by Bi-TA dressing. Overall, the Bi-TA with appropriate structural and multifunctional properties can be an excellent candidate for developing effective dressings for wound healing applications.

Injectable and self-healing chitosan-based hydrogel with MOF-loaded α-lipoic acid promotes diabetic wound healing

The difficulty of wound healing in patients with diabetes mellitus remains a considerable challenge for clinical and scientific research. To address the problem of poor healing that affects chronic wounds in patients with diabetes, we developed an injectable self-healing hydrogel based on chitosan (CS), hyaluronic acid (HA), and kalium γ-cyclodextrin metal organic frameworks (K-γ-CD-MOFs) loaded α-lipoic acid (α-LA) with antibacterial activity and antioxidant performance. In vitro analysis showed that the hydrogel could promote cell proliferation and migration on the basis of Cell Counting Kit-8 (CCK-8) assay and Transwell experiments. Moreover, the addition of α-LA allowed the reversal of oxidative stress-induced cell damage. In vivo analyses were performed involving a full-thickness wound model in diabetic Sprague–Dawley (SD) rats. The hydrogel dressing significantly promoted the wound healing process with better granulation tissue formation and more collagen deposition because of its multifunctional traits, suggesting that it can be an excellent treatment for chronic full-thickness skin wound healing.

Silk Fibroin/Spidroin Electrospun Scaffolds for Full-Thickness Skin Wound Healing in Rats.

The main goal of our research was to fabricate electrospun scaffolds from three different silk proteins—silk fibroin from Bombyx mori silkworm cocoons and two recombinant spidroins, rS2/12 and rS2/12-RGDS—and to perform a comparative analysis of the structure, biological properties, and regenerative potential of the scaffolds in a full-thickness rat skin wound model. The surface and internal structures were investigated using scanning electron microscopy and scanning probe nanotomography. The structures of the scaffolds were similar. The average fiber diameter of the scaffolds was 315 ± 26 nm, the volume porosity was 94.5 ± 1.4%, the surface-to-volume ratio of the scaffolds was 25.4 ± 4.2 μm−1 and the fiber surface roughness was 3.8 ± 0.6 nm. The scaffolds were characterized by a non-cytotoxicity effect and a high level of cytocompatibility with cells. The scaffolds also had high regenerative potential—the healing of the skin wound was accelerated by 19 days compared with the control. A histological analysis did not reveal any fragments of the experimental constructions or areas of inflammation. Thus, novel data on the structure and biological properties of the silk fibroin/spidroin electrospun scaffolds were obtained.

Comparison of the Therapeutic Effects of Native and Anionic Nanofibrillar Cellulose Hydrogels for Full-Thickness Skin Wound Healing

Nanofibrillar cellulose (NFC)-derived dressings such as films, hydrogels, and aerogels are one of the favorable materials for wound healing due to their proper mechanical properties and water holding ability. However, the therapeutic differences between native and anionic NFC materials are rarely studied. In this report, we compared the differences and addressed the regenerative potential of native and anionic wood-derived NFC hydrogels for wound treatment. In vitro characteristics of the hydrogels were detected using scanning electron microscopy, rheological measurements, and swelling and hemolytic activity assays. Skin regeneration at an early stage after hydrogel treatment was analyzed using an in vivo splinted excisional full-thickness skin wound model in C57BL/6 mice. Both native NFC and anionic NFC (ANFC) hydrogel with differing mechanical and surface properties were shown to be biocompatible. Surprisingly, wounds treated with NFC and ANFC hydrogel did not show any statistical difference compared with control wounds and progressed through normal wound closure, inflammatory response, re-epithelialization, vascularization, and tissue maturation with no signs of fibrosis. The data show here for the first time the therapeutic performance of native and anionic NFC hydrogel in a wound mimicking human wound healing mechanisms. The mechanical properties of native and anionic NFC hydrogels such as the capability to modify material stiffness may also prove to be valuable in the management of wounds in the future.

357 Angiogenin released from ABCB5+ MSCs Promotes Healing of Diabetic Wounds by triggering Angiogenesis

Diabetes mellitus is an urgent global health problem imposing a significant socioeconomic burden on societies. With high recurrence rates, non-healing wounds in diabetic patients are highly susceptible for necrosis due to ischemia and often progress to lower limb amputation. Severe angiopathy with reduced angiogenesis is a major driver for diabetes associated non-healing wounds. To dissect the underlying mechanisms, we here addressed the question whether administration of skin derived ABCB5+ MSCs, precursors of perivascular fibroblasts, can rescue suppressed angiogenesis and impaired wound healing in a full thickness wound model in diabetic mice.

Polyurethane-Nanolignin Composite Foam Coated with Propolis as a Platform for Wound Dressing: Synthesis and Characterization.

This piece of research explores porous nanocomposite polyurethane (PU) foam synthesis, containing nanolignin (NL), coated with natural antimicrobial propolis for wound dressing. PU foam was synthesized using polyethylene glycol, glycerol, NL, and 1, 6-diisocyanato-hexane (NCO/OH ratio: 1.2) and water as blowing agent. The resultant foam was immersed in ethanolic extract of propolis (EEP). PU, NL-PU, and PU-NL/EEP foams were characterized from mechanical, morphological, and chemical perspectives. NL Incorporation into PU increased mechanical strength, while EEP coating showed lower strength than PU-NL/EEP. Morphological investigations confirmed an open-celled structure with a pore diameter of 150–200 μm, a density of nearly 0.2 g/cm3,, and porosity greater than 85%, which led to significantly high water absorption (267% for PU-NL/EEP). The hydrophilic nature of foams, measured by the contact angle, proved to be increased by NL addition and EEP coating. PU and PU-NL did not show important antibacterial features, while EEP coating resulted in a significant antibacterial efficiency. All foams revealed high biocompatibility toward L929 fibroblasts, with the highest cell viability and cell attachment for PU-NL/EEP. In vivo wound healing using Wistar rats’ full-thickness skin wound model confirmed that PU-NL/EEP exhibited an essentially higher wound healing efficacy compared with other foams. Hence, PU-NL/EEP foam could be a promising wound dressing candidate.

Injectable stretchable self-healing dual dynamic network hydrogel as adhesive anti-oxidant wound dressing for photothermal clearance of bacteria and promoting wound healing of MRSA infected motion wounds

Due to the frequent movement and stretching of skin, traditional wound dressings are difficult to adapt to motion wounds on the stretchable parts of the body surface (e.g. elbow, hip and knee). Moreover, chronic motion wounds are often accompanied by infections. To address these issues, a series of injectable adhesive self-healing photothermal dual dynamic Schiff base network hydrogels were developed based on adipic dihydrazide modified hyaluronic acid, benzaldehyde group functionalized poly(ethylene glycol)–co-poly(glycerol sebacate) and cuttlefish melanin nanoparticles, and their excellent tissue adhesion, stretchability and self-healing properties enable them to adapt to the frequent movement of motion wounds. Meanwhile, the hydrogels can prevent and treat motion wound infections through photothermal antibacterial therapy, and exhibit multifunctions (including anti-oxidation, hemostasis, exudate absorption and sustained release property) to promote wound healing. In in vivo normal and infected full-thickness skin defect motion wound models, the hydrogel dressings significantly prevented wound infections and promoted wound healing with milder inflammation, higher granulation tissue thickness and collagen disposition. Overall, the adhesive self-healing photothermal hydrogels can adapt to frequent movement of motion wounds, and can improve infection and promote healing in both normal and infected motion wounds, indicating their great potential in motion wound treatment in clinics.

A novel anionic cathelicidin lacking direct antimicrobial activity but with potent anti-inflammatory and wound healing activities from the salamander Tylototriton kweichowensis

Cathelicidin is a family of antimicrobial peptides (AMPs) existing in vertebrates, which play multiple functions in host responses against environmental stresses. All cathelicidins identified to date are cationic, no anionic member with net negative charges has been reported. In the present study, a novel anionic cathelicidin (TK-CATH) with a net charge of −3 was identified from the skin of the salamander, T. kweichowensis. Unlike most other cathelicidin members, it didn't exhibit direct antimicrobial activity. However, it demonstrated strong anti-inflammatory activity. It effectively inhibited the LPS-induced pro-inflammatory cytokine gene expression and protein production in amphibian leukocytes and mouse macrophages by inhibiting the LPS-activated mitogen-activated protein kinase (MAPK) signaling pathways. Besides, TK-CATH showed potent wound healing activity. It could effectively induce the production of several cytokines, chemokines and growth factors relating to wound healing, promote the motility and proliferation of keratinocytes, and accelerate the skin wound healing in a mouse full-thickness wound model. These results imply that TK-CATH participates in both the inflammatory phase and new tissue formation phase of wound repair process. Meanwhile, TK-CATH exhibited weak but effective free radical scavenging activity and low cytotoxicity. All the results above indicate that TK-CATH is a multifunctional peptide in the skin of the salamander T. kweichowensis. It may play important roles in host immune responses against bacterial infection and skin wound repair.