Full-thickness Wound Healing Research Articles

Thymoquinone-Incorporated CollaGee Biomatrix: A Promising Approach for Full-Thickness Wound Healing

Wound infection is the leading cause of delayed wound healing. Despite ongoing research, the ideal treatment for full-thickness skin wounds is yet to be achieved. Skin tissue engineering provides an alternative treatment, with the potential for skin regeneration. Background/Objectives: Previously, we characterized a collagen–gelatin–elastin (CollaGee) acellular skin substitute and evaluated its cytocompatibility. The assessments revealed good physicochemical properties and cytocompatibility with human dermal fibroblasts (HDF). This study aimed to incorporate thymoquinone (TQ) as the antibacterial agent into CollaGee biomatrices and evaluate their cytocompatibility in vitro. Methods: Briefly, dose–response and antibacterial studies were conducted to confirm the antimicrobial activity and identify the suitable concentration for incorporation; 0.05 and 0.1 mg/mL concentrations were selected. Then, the cytocompatibility was evaluated quantitatively and qualitatively. Results: Cytocompatibility analysis revealed no toxicity towards HDFs, with 81.5 + 0.7% cell attachment and 99.27 + 1.6% cell viability. Specifically, the 0.05 mg/mL TQ concentration presented better viability, but the differences were not significant. Immunocytochemistry staining revealed the presence of collagen I, vinculin, and alpha smooth muscle actin within the three-dimensional biomatrices. Conclusions: These results suggest that TQ-incorporated CollaGee biomatrices are a promising candidate for enhancing the main key player, HDF, to efficiently regenerate the dermal layer in full-thickness skin wound healing. Further investigations are needed for future efficiency studies in animal models.

Troxerutin associated with Agaricus blazei Murill polysaccharides in films improves full-thickness wound healing

The present study aimed to associate troxerutin (TRX) with polysaccharides from Agaricus blazei Murill mushroom (PolyAb) in alginate/PVA films and evaluate their effect on wound healing. The physicochemical, mechanical, morphological, and water vapor barrier properties of the films were studied, and their biological potential was analyzed in vivo using the full-thickness wound healing model. The association between TRX and PolyAb present in the polymeric film contributed to increased thermal stability, mechanical resistance, and elasticity when compared to films without TRX, which indicated good miscibility of the excipients. In the in vivo tests, the TRX films promoted greater collagen deposition and repair of epidermis and dermis layers. The 0.25 % TRX film showed an increase in reduced glutathione levels, while the 1.0 % TRX film reduced lipid peroxidation and production of the pro-inflammatory cytokine IL-1β, demonstrating the anti-inflammatory and antioxidant effect of TRX films. Therefore, it is estimated that the film containing 1 % TRX can be used as biocurative for wound dressing applications.

Multi-functional Gleditsia sinensis galactomannan-based hydrogel with highly stretchable, adhesive, and antibacterial properties as wound dressing for accelerating wound healing

Design and development of a multifunctional wound dressing with self-healing, adhesive, and antibacterial properties to attain optimal wound closure efficiency are highly desirable in clinical applications. Nevertheless, conventional hydrogels face significant barriers in their mechanical strength, adhesive performance, and antibacterial properties. Herein, a tough hydrogel based on aldehyde-grafted galactomannan was synthesized through radical copolymerization and Schiff base reaction, incorporating hyaluronic acid, acrylamide, and the zwitterionic monomer to create a multi-crosslinked structure. The multiple crosslink structure pattern consisting of multiple hydrogen bonding, ionic interactions, reversible Schiff bases bonds, and molecular chain entanglement endowed this hydrogel with multiple functionalities, including high tensile strength (25 kPa), tensile strain (2200 %), toughness (391.59 kJ/m3), and Young's modulus (9.77 kPa). The presence of catechol groups and zwitterionic groups endow hydrogels with outstanding adhesion strength (42.21 kPa), which satisfied the adhesive demand for the ample motion of specific areas. The zwitterionic monomer provided long-lasting antibacterial properties and promoted migration and growth of negatively charged cells, capable of establishing efficient antibacterial barriers and serving as wound dressing. The in vivo and vitro experiments manifested that the optimized hydrogel demonstrated an inconspicuous inflammatory response, facilitating rapid healing of full-thickness skin wound in rat models. Therefore, this work provides a promising strategy and an ideal candidate for wound healing dressings in treating infected skin wounds.

Topical application of beta-blockers accelerates epithelialization to mesh skin grafted full-thickness burn in sheep

Aim : Beta-adrenergic receptor blockers are conventionally used for the treatment of hypertension, tachycardia, and glaucoma. Research has shown that beta-blockers can accelerate wound epithelialization. In this study, we tested the efficacy of the beta-blocker timolol in an ovine model of grafted full-thickness burn wound healing, which closely mimics clinical scenarios. Methods : Six full-thickness burn wounds were created on the sheep’s posterior surface. Twenty-four hours later, eschars were excised and meshed skin was grafted (Day0). The wounds in the treatment group received topical application of timolol. Blood flow was measured using a blood perfusion imager. Cardiovascular hemodynamics and blood glucose levels were recorded daily. The epithelialization rate on Day 14 was determined by planimetric assay and analyzed by paired t -test. The days that the epithelialization rate exceeded 85%, 90%, and 95% were analyzed by survival analysis. To assess the potential influence of TGFβ, epithelial-mesenchymal transition (EMT), or myofibroblast activation (MFA) on wound healing, the RNA abundance of gene products related to these pathways was measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). Results : The epithelialization rate on Day 14 was significantly higher in the treatment group. The days that the epithelialization rate exceeded 85%, 90%, and 95% were significantly shorter in the treatment group. There was no significant difference in wound blood flow or RNA abundance related to TGFβ, EMT, or MFA-related pathways among the groups at any time point. Conclusion : The results demonstrate that the beta-blocker timolol accelerates epithelialization of mesh skin grafted full-thickness burn wounds through a mechanism other than improving wound blood flow.

Development of low-molecular-weight polysaccharide-based wound dressings for full-thickness cutaneous wound healing via coacervate formation

The development of polysaccharide-based wound dressings that are easy to prepare, adhere to tissue, adapt to diverse shapes and exhibit tunable mechanical properties holds significant clinical interest. This study introduced a simple spontaneous liquid-liquid phase separation technique employing low-molecular-weight and high polyion concentration of chitosan (CS) and hyaluronic acid (HA) to fabricate CS/HA coacervates. Upon increasing the molecular weight of chitosan from 7 kDa to 250 kDa, a transition in the CS/HA coacervates from liquid-like state to an elastic liquid and eventually to a solid-like state was observed. The resulting CS/HA coacervates demonstrated robust water resistance and adhesion to skin tissue. Notably, the molecular weight of chitosan significantly influenced the mechanical properties and hydration levels of the CS/HA coacervates. Moreover, in vivo studies using a full-thickness cutaneous defect model revealed that the CS/HA coacervates, prepared using 100 kDa chitosan, markedly accelerate wound healing. The coacervates' ease of preparation, wet adhesion, heterogeneous structure, suitability for irregularly shaped wounds, and exceptional wound healing promotion of the coacervates qualify them as an optimal wound dressing.

An injectable hydrogel of porcine cholecyst extracellular matrix for accelerated wound healing.

Hydrogel formulations of xenogeneic extracellular matrices have been widely used for topical wound care because of their exceptional tunability over other formulations like lyophilized sheets, powders, non-injectable gels, pastes, and ointments. This is important in the treatment of wounds with irregular shapes and depth. This study identified an injectable hydrogel formulation of porcine cholecyst extracellular matrix (60%) in medical-grade carboxymethyl cellulose (40%) as vehicle and evaluated its biomaterial properties. Further, an in-depth evaluation of in vivo wound healing efficacy was conducted in a rat full-thickness skin excision wound healing model, which revealed that the hydrogel formulation accelerated wound healing process compared to wounds treated with a commercial formulation and untreated wounds. The hydrogel appeared to have promoted a desirable pro-regenerative tissue reaction predominated by Th2 helper lymphocytes and M2 macrophages as well as an effective collagen remodeling indicative of diminished scarring. In conclusion, the porcine cholecyst extracellular matrix injectable hydrogel formulation appeared to be a promising candidate formulation as an advanced wound care biomaterial for faster healing of skin wounds with minimal scarring.

Evaluation of a Kenaf Nanocrystalline Cellulose-based Hydrogel Containing Platelet Lysate for Full-thickness Wound Healing

Introduction: Healing full-thickness wounds is often challenging and time-consuming, with complications such as scarring and infections. The standard treatment, split skin grafting, has limitations due to the availability of healthy donors and suitability for immunocompromised patients. Method: Autologous platelet lysate (PL) has been popular for tissue regenerative potential because it contains growth factors (GF) and is a safer option for bedridden patients with weak immune systems. However, PL has inconsistent clinical efficacy, high costs, and a short half-life. To address these issues, this study explores a novel delivery system by fabricating a chitosan/nanocrystalline cellulose (CS/NCC) hydrogel to sustainably deliver autologous PL to the wound site. Notably, NCC was prepared from kenaf bast fibers using acid hydrolysis and integrated into the CS matrix through physical entrapment without any chemical crosslinkers. The composite hydrogel was then enriched with autologous PL and further characterized for its physicochemical properties, in vitro GF release, and compatibility with skin cells. At the molecular level, gene expression of wound healing genes was facilitated using qPCR, revealing that the PL-supplemented hydrogel upregulated the expression of extracellular matrix genes. An in vivo study using a full-thickness wound model demonstrated that the CS-NCC-PL hydrogel dressing achieved 81.8% wound closure within 14 days, compared to the control groups. Result: Histological analysis indicated enhanced re-epithelialization, angiogenesis, and collagen deposition. Particularly, the CS-NCC-PL hydrogel group showed a significantly higher hydroxyproline content (60.62 ± 11.46 μg/100 mg) by day 14. Immunohistochemistry results revealed elevated levels of α-SMA and CD31, markers of myofibroblast presence and angiogenesis, peaking at day 7. Conclusion: These findings suggest that the CS-NCC-PL hydrogel is a promising personalized wound dressing for bedridden patients, offering improved healing outcomes in hospital settings.

Accelerating the healing of full-thickness excision wounds in mice using piezoelectric direct discharge plasma

Accelerating the healing of full-thickness excision wounds in mice using piezoelectric direct discharge plasma

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 multifunctional polyacrylonitrile fibers/alginate-based hydrogel loaded with chamomile extract and silver sulfadiazine for full-thickness wound healing

Most conventional wound dressings do not meet the clinical requisites owing to their limited multifunctionality. Herein, a bilayer wound dressing containing both hydrogel and fibrous structures with multifunctional features was developed for effective skin rehabilitation. Sodium alginate (SA)/gelatin (Gel) hydrogel comprising Matricaria chamomilla L extract and silver sulfadiazine (AgSD) drug as antibacterial agents was cross-linked using genipin and CaCl2. Then, the surface of the hydrogel was covered by electrospun polyacrylonitrile (PAN) nanofibers to fabricate a bilayer dressing. FESEM images revealed formation of continuous, smooth, and bead-free PAN nanofibers with excellent compatibility between hydrogel and fibers. The bilayer wound dressing exhibited satisfactory mechanical virtues including elastic modulus (2.4 ± 0.2 MPa), tensile strength (6.2 ± 0.5 MPa) and elongation at break (21.8 ± 1 %) as well as suitable swelling ratio. Such bilayer dressing revealed biodegradability, cytocompatibility and effective antibacterial performance against gram positive and gram negative strains. Release kinetics of AgSD drug followed a Fickian diffusion mechanism, ensuring sustained drug release. In vivo studies demonstrated bilayer dressing could promote rate of wound closure, re-epithelialization and collagen deposition, facilitating the replacement of damaged skin with healthy tissue. Such engineered wound dressing has a high potency for inducing skin repair and could be used in skin tissue engineering.

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

Exploring the Therapeutic Potential of Bee Venom Components in Wound Healing: A Comprehensive Evaluation of Morphometric, Biochemical, and Histopathological Markers

Abstract Bee venom (BV) and its components, secretory phospholipase A2 (sPLA2) and Apis cerana secapin-1 (AcSecapin-1), have potential effects on wound healing. This study aims to evaluate impact of BV, sPLA2, and AcSecapin-1 on full-thickness wound healing in male Wistar Albino rats over a 7-day period. Various morphometric (body weight, wound contraction), biochemical (hydroxyproline, oleic acid, IL-8, TGF-β1, redox parameters), and histopathological markers (reepithelialization, inflammatory cells, angiogenesis, fibroblast activation, and collagen density) were assessed. Treatment with sPLA2 and AcSecapin-1 increased oleic acid levels. IL-8 levels increased with sPLA2 treatment, and TGF-β1 levels increased with AcSecapin-1 treatment. BV and its components led to a decrease in FRAP levels. Additionally, BV treatment resulted in reduced angiogenesis, and both BV and sPLA2 treatments reduced inflammatory cells. All groups exhibited wound contraction without delay or regression. sPLA2 and AcSecapin-1 induced alterations in the wound healing milieu, without systemic changes. The treatment groups, except for the AcSecapin-1 group, showed an anti-inflammatory effect, identified by reduced inflammatory cell accumulation. Only the BV treatment suppressed angiogenesis. In conclusion, BV, sPLA2, and AcSecapin-1 demonstrate distinct effects on wound healing, with BV showing notable anti-inflammatory and anti-angiogenic properties, while sPLA2 and AcSecapin-1 influenced cytokine and oleic acid levels.

Comparison of different modern wound dressings on full-thickness murine cutaneous wound healing with wild-type and type-2 diabetes db/db mice

BackgroundTo evaluate the process of cutaneous wound healing, experiments have been conducted. However, to date, what modern wound dressings are suitable remains unclear. Therefore, this study aimed to compare the healing process in different modern wound dressings to determine their suitability in experimental acute wound and chronic diabetic wound. Materials and methodsTwelve C57BL/6J mice and eleven db/db mice were subjected to full-thickness wound injuries. The mice were divided into the following four groups: hydrocolloid, form, film, and gauze groups in both wild-type and db/db mice. Wound healing was assessed until day 14. ResultsIn the wild-type groups, all wounds were healed and completed re-epithelialization by day 14. However, the wound surface was dry, and the periwound was hypercontracted in the wild-type–form and wild-type–gauze groups. In the db/db groups, wounds were not healed until day 14. Wound exudates in the db/db- hydrocolloid group were abundant and gradually increased until day 14. Wound exudates in the db/db-film group were present until day 14. Conversely, in the db/db-form and db/db-gauze groups, the wound surface was dry, and the periwound was hypercontracted. ConclusionThese results showed that hydrocolloid and film dressings are suitable modern wound dressings for the mice wound models of acute wound and chronic diabetic wound. Moreover, using either hydrocolloid or film dressing depending on the purpose of the study on cutaneous wound healing in diabetes is necessary.

Multifunctional nanofibrous scaffolds for enhancing full-thickness wound healing loaded with Bletilla striata polysaccharides

The considerable challenge of wound healing remains. In this study, we fabricated a novel multifunctional core-shell nanofibrous scaffold named EGF@BSP-CeO2/PLGA (EBCP), which is composed of Bletilla striata polysaccharide (BSP), Ceria nanozyme (CeO2) and epidermal growth factor (EGF) as the core and poly(lactic-co-glycolic acid) (PLGA) as the shell via an emulsion electrospinning technique. An increase in the BSP content within the scaffolds corresponded to improved wound healing performance. These scaffolds exhibited increased hydrophilicity and porosity and improved mechanical properties and anti-UV properties. EBCP exhibited sustained release, and the degradation rate was <4 % in PBS for 30 days. The superior biocompatibility was confirmed by the MTT assay, hemolysis, and H&E staining. In addition, the in vitro results revealed that, compared with the other groups, the EBCP group presented excellent antioxidant and antibacterial effects. More importantly, the in vivo results indicated that the wound closure rate of the EBCP group reached 94.0 % on day 10 in the presence of H2O2. The results demonstrated that EBCP could comprehensively regulate the wound microenvironment, possess hemostatic abilities, and significantly promote wound healing. In conclusion, the EBCP is promising for facilitating the treatment of infected wounds and represents a potential material for clinical applications.

Injectable antibacterial hydrogels based on oligolysines for wound healing

Generally, oligolysine has poor antibacterial effect and almost no antibacterial activity. Herein, low cost and easily available oligolysines were chosen to prepare injectable antibacterial hydrogel (PVAL-gel) for wound healing. The hydrogel network was formed by cross-linking vanillin acrylate-N, N-dimethylacrylamide copolymer P(VA-co-DMA), oligolysine and adipate dihydrazide through Schiff base bond. The obtained hydrogel PVAL-gel exhibited not only excellent self-healing capability and injectability, but also the efficient contact antibacterial ability and good inhibitory effects on E.coli and S.aureus. In vitro, 99.9 % of pathogenic bacteria was killed within 160 min. Furthermore, the injectable PVAL-gel could rapidly eradicate bacteria in infected wounds and notably enhance the healing of full-thickness skin wounds. Therefore, PVAL-gel is expected to be used as a high-end dressing for the treatment of infected skin wounds, which can promote wound healing.

Electrospun collagen/chitosan composite fibrous membranes for accelerating wound healing

The protein-polysaccharide nanofibers have attracted intensive attention in promoting wound healing, due to their components and nanoscale fibrous structure that mimics the native extracellular matrix (ECM). For the full-thickness wounds, in addition to promoting healing, hemostatic property and antibacterial activity are also of critical importance. However, currently, protein-polysaccharide-based nanofiber membranes exhibit poor mechanical properties, lack inherent hemostatic and antibacterial capabilities, as well as the ability to promote tissue repair. In this study, we developed composited membranes, which were composed of collagen (Col) and chitosan (Chs), through solvent alteration and post-processing, the membranes showed enhanced stability under physiological conditions, proper hydrophilic performance and improved mechanical property. Appropriated porosity and water vapor transmission rate, which benefit to wound healing, were detected among all the membranes except for Col membrane. Aimed at wound dressing, hemocompatibility, antibacterial activity and cell proliferation of the electrospun membranes were evaluated. The results indicated that the Col/Chs composited membranes exhibited superior blood clotting capacity, and the membranes with Chs exceeding 60% possessed sufficient antibacterial activity. Moreover, compared with Chs nanofibers, significant increase in cell grow was detected in Col/Chs (1:3) membrane. Taken together, the electrospun membrane with multiple properties favorable to wound healing, superior blood coagulation, sufficient antibacterial performance and promoting cell proliferation property make it favorable candidate for full-thickness skin wound healing.

Tannic acid-modified acellular dermal matrix dressings for promoting full-thickness wound healing

Wound healing is a significant clinical and public health concern, and wound dressings are currently the primary method for addressing it. This study aimed to develop a multifunctional, all-natural wound dressing with antibacterial and anti-inflammatory properties using porcine acellular dermal matrix (PADM), a bioderived material that closely resembles the structure of human skin. The cells were decellularized using hypertonic salt and strong alkaline to remove immunogenicity while retaining the extracellular matrix. Subsequently, the wound dressing was prepared through tannic acid modification. In vitro cytotoxicity, scratch, anti-inflammatory, and antibacterial tests were used to assess the multifunctionality of the biomaterials. A full-thickness skin defect wound was created in rats, and the wound healing was analyzed using gross and histological staining. The results indicated that tannic acid-modified acellular dermal matrix exhibits favorable mechanical properties and biocompatibility. In vitro experiments demonstrated its effective inhibition of the growth of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. It can downregulate nitric oxide (NO) production and the expression levels of pro-inflammatory factors in macrophages stimulated by lipopolysaccharide. In vitro experiments demonstrated that the dressing can enhance wound healing. Therefore, tannic acid-modified acellular dermal matrix accelerates wound healing through anti-inflammatory and antibacterial effects. Its excellent properties make it a potential biological material for promoting wound healing.

A bioactive xyloglucan polysaccharide hydrogel mechanically enhanced by Pluronic F127 micelles for promoting chronic wound healing

Chronic wounds represent a formidable global healthcare challenge due to the bacteria infections and uncontrollable inflammation responses, while developing wound healing materials capable of resolving these issues remains a challenge. In this study, we integrated xyloglucan (XG) with Pluronic F127 diacrylate (F127DA)to develop a composite hydrogel for wound healing, where the XG introduced anti-inflammation and anti-bacterial properties to the construct, and F127DA provides the photocurable properties essential for hydrogel formation and robust mechanical characteristics to achieve physical strength that matches tissue regeneration. The material characterizations suggested that XG/F127DA hydrogels had great biostability, blood compatibility and antibacterial effects, which was suitable to be used as a wound healing material. The in vitro analysis by culturing L929 fibroblasts on the hydrogel surface demonstrated that the inclusion of XG could promote the cellular proliferation rate, migration rate, and re-epithelialization-related marker expression, while downregulate the inflammation process. The XG/F127DA hydrogel was further used for the full-thickness skin wound healing test on mice, where the inclusion of XG significantly increased the wound closure rate through reducing the inflammation responses, and promote re-epithelialization and angiogenesis. These results indicated that XG/F127DA hydrogel has great potential to be used for wound healing in future clinical translation.

Fast Self-Healing Hyaluronic Acid Hydrogel with a Double-Dynamic Network for Skin Wound Repair.

Developing extracellular matrix-derived hydrogel with a fast self-healing capacity to provide a sustainable moist environment able to accelerate wound healing is highly desired for full-thickness skin wound repair. In this study, a fast self-healing hyaluronic acid hydrogel with a dual dynamic network was constructed through a primary reversible acylhydrazone bond formed between aldehyde-modified hyaluronic acid, 3,3'-dithiobis (propionyl hydrazide) (DTP), and secondary dynamic ionic interactions between κ-carrageenan (KC) and K+. Because of the presence of various dynamic covalent bonds such as the acylhydrazone bond, disulfide bond, and noncovalent bonds including hydrogen bonding and ionic interactions, as well as the notable thermoreversible nature of KC, the resultant hydrogel could be self-healed rapidly within 30 min under physiological temperature with a self-healing efficiency of 100%, which was significantly better than other hyaluronic acid hydrogels, as reported previously. Besides, the hydrogel displayed excellent cytocompatibility. According to this study, the hydrogel was administered into the wounds and achieved a superior performance of promoting full-thickness skin wound healing by increasing granulation tissue formation, deposition of collagen as well as the acceleration of re-epithelialization and neovascularization, compared to commercial products, e.g., gauze and 3 M hydrocolloid. We also anticipate that this strategy of double-dynamic network cross-linking can be adopted to fabricate self-healing materials for multiple applications.

A green, ROS-scavenging and anti-bacterial hydrogel loading MnO2-curcumin nanocomposite for the full-thickness wound healing

Recently, nanozymes have been widely applied for the enhancement of reactive oxygen species (ROS) and hypoxia, which is a major obstacle to the quick repairing of skin wound. However, their intrinsic low bioavailability and biosafety is still a great challenge for the broad introduction in the wound healing. Meanwhile, the fabrication of hydrogel wound dressing mostly accompany the complicated polymer modification, synthetic polymer usage and following pollution and health risk. Nanocellulose (CNC) has been remarked as a good candidate for functional hydrogel dressing, however, its role is generally confined to a simple mechanical reinforce or Schiff base participant in the oxidized form. With this regards, in the present paper, we first developed a ROS-scavenging, MnO2-curcumin nanocomplex stabilized by bovine serum albumin (BSA) (called BMC NPs). Dopamine was oxidative polymerized on the nanocellulose chain to form the CNC-polydopamine (CNC-PDA) in a facile way, and cross-linked quickly with thiol-fortified gelatin (Gel-SH) via the catechol-thiol addition to produce the adhesive, self-healing and hemostatic hydrogel. The CNC-PDA + Gel-SH hydrogel loading BMC NPs showed an excellent anti-oxidant, and anti-bacterial capacity. In vivo full-thickness wound experiment also confirmed that CNC-PDA + Gel-SH + BMC NPs hydrogel has a good re-epithelization, collagen synthesis, ROS clearance and anti-inflammation with the NIR treatment. Our result demonstrates the promising effect of nanocomposite -biomolecule conjugate in the wound healing as well as the great potential of PDA-coating chemistry in the hydrogel preparation.