Project description:Wound healing is a major burden of healthcare systems worldwide and hydrogel dressings offer a moist environment conducive to healing. We describe cysteine-containing ultrashort peptides that self-assemble spontaneously into hydrogels. After disulfide crosslinking, the optically-transparent hydrogels became significantly stiffer and exhibited high shape fidelity. The peptide sequence (LIVAGKC or LK6C) was then chosen for evaluation on mice with full-thickness excision wounds. Crosslinked LK6C hydrogels are handled easily with forceps during surgical procedures and offer an improvement over our earlier study of a non-crosslinked peptide hydrogel for burn wounds. LK6C showed low allergenic potential and failed to provoke any sensitivity when administered to guinea pigs in the Magnusson-Kligman maximization test. When applied topically as a dressing, the medium-infused LK6C hydrogel accelerated re-epithelialization compared to controls. The peptide hydrogel is thus safe for topical application and promotes a superior rate and quality of wound healing.
Project description:Hydrogels have been widely used in various biomedical applications, including skin regeneration and tissue repair. However, the capability of certain hydrogels to absorb exudate or blood from surrounding wounds, coupled with the challenge in their long-term storage to prevent bacterial growth, can pose limitations to their efficacy in biological applications. To address these challenges, the development of a multifunctional aloin-arginine-alginate (short for 3A) bio-patch capable of transforming into a hydrogel upon absorbing exudate or blood from neighboring wounds for cutaneous regeneration is proposed. The 3A bio-patch exhibits outstanding features, including an excellent porous structure, swelling properties, and biodegradability. These characteristics allow for the rapid absorption of wound exudates and subsequent transformation into a hydrogel that is suitable for treating skin wounds. Furthermore, the 3A bio-patch exhibits remarkable antibacterial and anti-inflammatory properties, leading to accelerated wound healing and scarless repair in vivo. This study presents a novel approach to the development of cutaneous wound dressing materials.
Project description:Mesenchymal stem cell derived exosomes (MSC-Exos) demonstrate beneficial effects on wound healing via anti-inflammatory and angiogenic properties. Chitosan (CS) exhibits excellent biocompatibility and accelerates cellular migration, adhesion, and proliferation. The ions released from bioactive glass (BG) and titanium dioxide (TiO2) nanoparticles exhibit sustained angiogenic and antibacterial potency. In this study, CMCS-CEBT hydrogel was synthesized from exosomes encapsulated carboxymethyl chitosan (CMCS), chitosan nanoparticles (CS-NPs), BG, and TiO2 nanoparticles for a preliminary evaluation of its impacts on the treatment of full-thickness skin defects, diabetic wounds, and burn skin injury due to burns. In vitro analysis indicated that the hydrogel exhibits excellent cell compatibility, stimulates endothelial cell adhesion and proliferation, and presents anti-inflammatory, angiogenic, and antibacterial activities. In vivo, the composite hydrogel dressing accelerated a wound healing acceleration effect, stimulated angiogenesis, and increased collagen deposition and the expression of anti-inflammatory factors. This innovative composite hydrogel dressing as a potential clinical therapy, utilizing bioactive materials, holds promise as a potential clinical therapy that aims to facilitate the regeneration of acute and chronically damaged skin tissue.
Project description:Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF-Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing.
Project description:Gelatin-based hydrogels have a broad range of biomedical fields due to their biocompatibility, convenience for chemical modifications, and degradability. However, gelatin-based hydrogels present poor antibacterial ability that hinders their applications in treating infected wound healing. Herein, a series of multifunctional hydrogels (Gel@Zn) were fabricated through free-radical polymerization interaction based on gelatin methacrylate (GelMA) and dopamine methacrylate (DMA), and then immersed them into zinc nitrate solutions based on the metal coordination and ionic bonding interaction. These designed hydrogels wound dressings show strong antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by increasing intracellular reactive oxygen species (ROS) level and changing bacterial membrane permeability. Meanwhile, the hydrogels exhibit good cytocompatibility, enhance the adhesion, proliferation, and migration of NIH-3T3 cells. Furthermore, Gel@Zn-0.08 (0.08 M Zn2+ immersed with Gel sample) presents a good balance between antibacterial effect, cell viability, and hemolytic property. Compared with 3 M commercial dressings, Gel@Zn-0.04, and Gel@Zn-0.16, the Gel@Zn-0.08 could significantly improve the healing process of S. aureus-infected full-thickness wounds via restrained the inflammatory responses, enhanced epidermis and granulation tissue information, and stimulated angiogenesis. Our study indicates that the Zn-incorporated hydrogels are promising bioactive materials as wound dressings for infected full-thickness wound healing and skin regeneration.
Project description:Globally, wound infection is considered to be one of the major healthcare problems, with bacterial infections being the most critical threat, leading to poor and delayed wound healing, and even death. As a superbug, methicillin-resistant Staphylococcus aureus (MRSA) causes a profound hazard to public health safety, prompting us to search for alternative treatment approaches. Herein, the MTT test and Hoechst/propidium iodide (PI) staining demonstrated that PD was slightly less toxic to human fibroblasts including Human keratinocytes (HaCaT) cell line than Silver sulfadiazine (SSD), and Vancomycin (Van). In the MRSA-infected wound model, PD hydrogel (1%, 2.5%) was applied with for 14 days. The wound healing of PD hydrogel groups was superior to the SSD, Van, and control groups. Remarkably, the experimental results showed that PD reduced the number of skin bacteria, reduced inflammation, and upregulated the expression of PCNA (keratinocyte proliferation marker) and CD31 (angiogenesis manufacturer) at the wound site by histology (including hematoxylin-eosin (HE) staining, Masson staining) and immunohistochemistry. Additionally, no toxicity, hemocompatibility or histopathological changes to organs were observed. Altogether, these results suggested the potential of PD hydrogel as a safe, effective, and low toxicity hydrogel for the future clinical treatment of MRSA-infected wounds.
Project description:BackgroundWound healing is a process that requires angiogenesis and antibacterial activities and it remains a challenge for both experimental and clinical research worldwide. Zn2+ has been reported to be widely involved in angiogenesis and exerts antibacterial effects, making it suitable as a treatment to promote wound healing. Therefore Zn2+-loaded adhesive bacterial cellulose hydrogel was designed to observe its angiogenic and antibacterial abilities in the wound healing process.MethodsThe characterization, tensile strength, swelling behaviors and antibacterial activity of bacterial cellulose/polydopamine/zeolitic imidazolate framework-8 (BC/PDA/ZIF8) hydrogels were tested. Cell-Counting-Kit-8 (CCK8), transwell, tube formation and real time qunantitative PCR (qRT-PCR) assays were performed to evaluate the cell compatibility of BC/PDA/ZIF8 hydrogels in vitro. A full-thickness defect wound model and histological assays were used to evaluate the BC/PDA/ZIF8 hydrogels in vivo.ResultsThe prepared BC/PDA/ZIF8 hydrogels exhibited suitable mechanical strength, excellent swelling properties, good tissue adhesion, efficient angiogenic and antibacterial effects and good performance as a physical barrier. In vivo experiments showed that the BC/PDA/ZIF8 hydrogels accelerated wound healing in a full-thickness defect wound model by stimulating angiogenesis.ConclusionsThis study proved that BC/PDA/ZIF8 hydrogels possess great potential for promoting satisfactory wound healing in full-thickness wound defects through antibacterial effects and improved cell proliferation, tissue formation, remodeling and re-epithelialization.
Project description:The development of biological macromolecule hydrogel dressings with fatigue resistance, sufficient mechanical strength, and versatility in clinical treatment is critical for accelerating full-thickness healing of skin wounds. Therefore, in this study, multifunctional, biological macromolecule hydrogels based on a recombinant type I collagen/chitosan scaffold incorporated with a metal-polyphenol structure were fabricated to accelerate wound healing. The resulting biological macromolecule hydrogel possesses sufficient mechanical strength, fatigue resistance, and healing properties, including antibacterial, antioxygenic, self-healing, vascularization, hemostatic, and adhesive abilities. Chitosan and recombinant type I collagen formed the scaffold network, which was the first covalent crosslinking network of the hydrogel. The second physical crosslinking network comprised the coordination of a metal-polyphenol structure, i.e., Cu2+ with the catechol group of dopamine methacrylamide (DMA) and stacking of DMA benzene rings. Double-crosslinked networks are interspersed and intertwined in the hydrogel to reduce the mechanical strength and increase its fatigue resistance, making it more suitable for clinical applications. Moreover, the biological macromolecule hydrogel can continuously release Cu2+, which provides strong antibacterial and vascularization properties. An in vivo full-thickness skin defect model confirmed that multifunctional, biological macromolecule hydrogels based on a recombinant type I collagen/chitosan scaffold incorporated with a metal-polyphenol structure can facilitate the formation of granulation tissue and collagen deposition for a short period to promote wound healing. This study highlights that this biological macromolecule hydrogel is a promising acute wound-healing dressing for biomedical applications.
Project description:In vivo, multidomain peptide (MDP) hydrogels undergo rapid cell infiltration and elicit a mild inflammatory response which promotes angiogenesis. Over time, the nanofibers are degraded and a natural collagen-based extracellular matrix is produced remodeling the artificial material into natural tissue. These properties make MDPs particularly well suited for applications in regeneration. In this work, we test the regenerative potential of MDP hydrogels in a diabetic wound healing model. When applied to full-thickness dermal wounds in genetically diabetic mice, the MDP hydrogel resulted in significantly accelerated wound healing compared to a clinically used hydrogel, as well as a control buffer. Treatment with the MDP hydrogel resulted in wound closure in 14 days, formation of thick granulation tissue including dense vascularization, innervation, and hair follicle regeneration. This suggests the MDP hydrogel could be an attractive choice for treatment of wounds in diabetic patients.
Project description:Rapid post-wound closure is necessary to avoid wound infection and promote scar-free healing when skin trauma occurs. In this study, new types of hydrogel dressings with adjustable contractility were fabricated based on N-isopropyl acrylamide/sodium alginate/graphene oxide (P/SA/GO). Then, the chitosan (CS) solution was used as a bridging polymer to achieve tissue adhesion to the hydrogel. The results show that the hydrogel based on poly(N-isopropyl acrylamide) (PNIPAM) not only has the ability to self-shrink but also can adjust the rate of shrinkage through near-infrared thermal stimulation. At the same time, high adhesion strength (7.86 ± 1.22 kPa) between the tissue and the dressing is achieved through the introduction of bridging polymers (CS), and the coating area of the bridging polymer can be adjusted to achieve regional adhesion. The mouse total skin defects experiments have shown that sutures-free wound closure in the early stages of wound healing could be obtained by adjusting the material temperature. Besides, the dressings can promote scar-free wound healing by reducing inflammatory cell infiltration and collagen deposition. These results indicate that double-crosslinked PNIPAM-based hydrogel dressings with adjustable adhesion and contractility proposed in this study provide a candidate material for achieving trackless wound healing.