Chitosan–hyaluronic acid hybrid film as a novel wound dressing: in vitro and in vivo studies

Wound dressing with high quality is a kind of highly demanded wound‐repairing products. In this article, chitosan (CS) and hyaluronic acid (HA) were used to fabricate a novel wound dressing. CS/HA composite films with high transparency could be fabricated on glass or poly(methyl methacrylate) (PMMA) substrates, but not on poly(tetrafluoroethylene) (PTFE) plate. Along with the increase of HA amount, the resulting films became rougher as detected by atomic force microscopy (AFM). Increased also are water contact angle and water‐uptake ratio. By contrast, increase of the HA amount weakened the water vapor permeability (WVP), bovine albumin adsorption, and fibroblast adhesion, which are desirable characteristics for wound dressing. In vivo animal test revealed that compared with the vaseline gauge the CS/HA film could more effectively accelerate the wound healing, and reduce the occurrence of re‐injury when peeling off the dressing again. These results demonstrate that the CS mixed with a little amount of HA may produce inexpensive wound dressing with good properties for practical applications. Copyright © 2007 John Wiley & Sons, Ltd.     

Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca²⁺, and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.     

A Bi‐Layer PVA/CMC/PEG Hydrogel with Gradually Changing Pore Sizes for Wound Dressing

Wound dressings are vital for cutaneous wound healing. In this study, a bi‐layer dressing composed of polyvinyl alcohol/carboxymethyl cellulose/polyethylene glycol (PVA/CMC/PEG) hydrogels is produced through a thawing–freezing method based on the study of the pore size of single‐layer hydrogels. Then the physical properties and healing of full‐thickness skin defects treated with hydrogels are inspected. The results show that the pore size of the single‐layer PVA/CMC/PEG hyrogel can be controlled. The obtained non‐adhesive bi‐layer hydrogels show gradually increasing pore sizes from the upper to the lower layer and two layers are well bonded. In addition, bi‐layer dressings with good mechanical properties can effectively prevent bacterial penetration and control the moisture loss of wounds to maintain a humid environment for wounds. A full‐thickness skin defect test shows that bi‐layer hydrogels can significantly accelerate wound closure. The experiment indicates that the bi‐layer PVA/CMC/PEG hydrogels can be used as potential wound dressings.     

Mussel-Inspired Adhesive,Antibacterial, and Stretchable Composite Hydrogel for Wound Dressing

Hydrogels have attracted extensive attention in the field of biomedicine because of their similar structure to extracellular matrix (ECM) and good biocompatibility. However, the adhesiveness, mechanical properties, and antibacterial properties of conventional hydrogels are not satisfactory. In this study, multifunctional chitosan/polydopamine/polyacrylamide (CS/PDA/PAM) hydrogels are prepared through a nature-inspired strategy. The catechol group of polydopamine (PDA) component endows CS/PDA/PAM hydrogels with tissue adhesion and self-healing properties. The introduction of chitosan (CS) not only greatly improves antibacterial ability, but also enhances the mechanical properties of CS/PDA/PAM hydrogels. Skin wound healing experiments show that CS/PDA/PAM hydrogels could accelerate skin tissue regeneration and promote wound healing. Therefore, CS/PDA/PAM hydrogels have great potential in the application of new wound dressings.     

Evaluation of a non-woven fabric coated with a chitosan bi-layer composite for wound dressing

This study presents a novel design of an easily stripped bi-layer composite that consists of an upper layer of a soybean protein non-woven fabric coated with a lower layer, a genipin-crosslinked chitosan film, as a wound dressing material. This study examines the in vitro properties of the genipin-crosslinked chitosan film and the bi-layer composite. Furthermore, in vivo experiments are conducted to study wounds treated with the composite in a rat model. Experimental results show that the degree of crosslinking and the in vitro degradation rate of the genipin-crosslinked chitosan films can be controlled by varying the genipin contents. In addition, the genipin contents should exceed 0.025 wt.-% of the chitosan-based material if complete crosslinking reactions between genipin and chitosan molecules are required. Water contact angle analysis shows that the genipin-crosslinked chitosan film is not highly hydrophilic; therefore, the genipin-crosslinked chitosan layer is not entangled with the soybean protein non-woven fabric, which forms an easily stripped interface layer between them. Furthermore, this new wound dressing material provides adequate moisture, thereby minimizing the risk of wound dehydration, and exhibits good mechanical properties. The in vivo histological assessment results reveal that epithelialization and reconstruction of the wound are achieved by covering the wound with the composite, and the composite is easily stripped from the wound surface without damaging newly regenerated tissue.     

Designing New Antibacterial Wound Dressings: Development of a Dual Layer Cotton Material Coated with Poly(Vinyl Alcohol)_Chitosan Nanofibers Incorporating Agrimonia eupatoria L. Extract

Wounds display particular vulnerability to microbial invasion and infections by pathogenic bacteria. Therefore, to reduce the risk of wound infections, researchers have expended considerable energy on developing advanced therapeutic dressings, such as electrospun membranes containing antimicrobial agents. Among the most used antimicrobial agents, medicinal plant extracts demonstrate considerable potential for clinical use, due primarily to their efficacy allied to relatively low incidence of adverse side-effects. In this context, the present work aimed to develop a unique dual-layer composite material with enhanced antibacterial activity derived from a coating layer of Poly(vinyl alcohol) (PVA) and Chitosan (CS) containing Agrimonia eupatoria L. (AG). This novel material has properties that facilitate it being electrospun above a conventional cotton gauze bandage pre-treated with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical (TEMPO). The produced dual-layer composite material demonstrated features attractive in production of wound dressings, specifically, wettability, porosity, and swelling capacity. Moreover, antibacterial assays showed that AG-incorporated into PVA_CS’s coating layer could effectively inhibit Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) growth. Equally important, the cytotoxic profile of the dual-layer material in normal human dermal fibroblast (NHDF) cells demonstrated biocompatibility. In summary, these data provide initial confidence that the TEMPO-oxidized cotton/PVA_CS dressing material containing AG extract demonstrates adequate mechanical attributes for use as a wound dressing and represents a promising approach to prevention of bacterial wound contamination.     

Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing

Anti-infection and neovascularization at the wound site are two vital factors that accelerate diabetic wound healing. However, for a wound healing dressing, the two functions need to work at different sites(inner and outer), giving big challenges for dressing design. In this study, we fabricated a novel sodium alginate/chitosan(SA/CS) Janus hydrogel dressing by the assembly of SA hydrogel loaded with silver nanoparticles(Ag NPs) and CS hydrogel impregnated with L-arginine loaded sodium alginate ...     

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.     

聚乙烯醇/聚乙烯吡咯烷酮/碘复合水凝胶的制备与性能

采用低温冷冻的方法, 通过改变聚乙烯醇(PVA)和聚乙烯吡咯烷酮碘络合物(PVP-I)的配比、 冷冻时间、 冷冻-解冻循环次数, 制备出一种可调控力学性能的PVA/PVP-I复合水凝胶. 研究了该复合水凝胶的机械 性能、 微观结构、 碘缓释性能和抑菌性质. 研究结果表明, PVA/PVP-I复合水凝胶可调控的力学性质可以满足伤口敷料对水凝胶力学性质的需求; 复合水凝胶的网络结构可以有效降低碘在紫外线下的分解速度, 实现对碘的稳定保护作用及控制释放, 从而发挥水凝胶持续抑菌性能, 为抑菌水凝胶的设计制备提供了新思路.     

Construction of Antibacterial N‐Halamine Polymer Nanomaterials Capable of Bacterial Membrane Disruption for Efficient Anti‐Infective Wound Therapy

The increasing occurrence of bacterial infection at the wound sites is a serious global problem, demanding the rapid development of new antibacterial materials for wound dressing to avoid the abuse of antibiotics and thereby antibiotic resistance. In this work, the authors first report on antibacterial N‐halamine polymer nanomaterials based on a strategic copolymerization of 3‐allyl‐5,5‐dimethylhydantoin (ADMH) and methyl methacrylate (MMA), which exhibits in vitro and in vivo antimicrobial efficacy against pathogenic bacteria including Staphylococcus aureus and Escherichia coli. Particularly, when a biological evaluation is run for wound therapy, the N‐halamine polymer nanomaterials exhibit a powerful antibacterial efficiency and wound healing ability after a series of histological examination of mouse wound. After the evaluation of biological and chemical surroundings, the proposed four‐stage mechanism suggests that, with unique antibacterial N? Cl bonds, the N‐halamine polymer nanomaterials can disrupt the bacterial membrane, as a result causing intracellular content leaked out and thereby cell death. Based on the synergistic action of antibacterial and wound therapy, the N‐halamine polymer nanomaterials are expected to be promising as wound dressing materials in medical healing and biomaterials.     

Dual‐Functional Dextran‐PEG Hydrogel as an Antimicrobial Biomedical Material

Microbial infections continually present a major worldwide public healthcare threat, particularly in instances of impaired wound healing and biomedical implant fouling. The development of new materials with the desired antimicrobial property to avoid and treat wound infection is urgently needed in wound care management. This study reports a novel dual‐functional biodegradable dextran‐poly(ethylene glycol) (PEG) hydrogel covalently conjugated with antibacterial Polymyxin B and Vancomycin (Vanco). The hydrogel is designed as a specialized wound dressing that eradicates existing bacteria and inhibits further bacteria growth, while, ameliorating the side effects of antibiotics and accelerating tissue repair and regeneration. The hydrogel exhibits potent antibacterial activities against both gram‐negative bacteria Escherichia coli (E. coli) and gram‐positive bacteria Staphylococcus aureus (S. aureus) with no observable toxicity to mouse fibroblast cell line NIH 3T3. These results demonstrate the immense potential of dextran‐PEG hydrogel as a wound dressing healthcare material in efficiently controlling bacteria growth in complex biological systems.     

Wound healing improvement by curcumin‐loaded electrospun nanofibers and BFP‐MSCs as a bioactive dressing

Wound healing, one of the most complex processes of the body involving the cooperation of several important biomolecules and pathways, is one of the major therapeutic and economic issues in regenerative medicine. The present study aimed to introduce a novel electrospun curcumin (Cur)‐incorporated chitosan/polyvinyl alcohol/carbopol/polycaprolactone nanofibrous composite for concurrent delivery of the buccal fat pad‐derived mesenchymal stem cells (BFP‐MSCs) and Cur to a full‐thickness wound on the mouse model. Scaffolds were characterized structurally using scanning electron microscopy (SEM), fluorescence microscopy imaging and Fourier‐transform infrared spectroscopy, and toxicity of the scaffolds was also evaluated after BFP‐MSC seeding by SEM imaging and 3‐(4,5 dimethyiazol‐2‐1)‐2‐5‐diphenyl tetrazolium bromide (MTT) assay. Then, its influence on the wound‐healing process was investigated as a wound dressing for a full‐thickness skin defect in mouse model. Results demonstrated that the designed composite scaffolds have the capability for cell seeding and support their growth and proliferation. Macroscopic and histopathological characteristics were evaluated at the end of the 7 and 14 days after surgery, and their results showed that our designed scaffold groups accelerated the wound‐healing process compared with the control group. Among those, scaffold/Cur, scaffold/Cur/BFP‐MSC and scaffold/BFP‐MSC groups demonstrated more wound repair efficacy. These results indicated that the combined grafts can be used to improve the wound‐healing process, and therefore, the electrospun nanofibers presented in this study, Cur and BFP‐MSC together, were demonstrated to have promising potential for wound‐dressing applications.     

One Step Fabrication and Application of Antibacterial Electrospun Zein/Cinnamon Oil Membrane Wound Dressing via In situ Electrospinning Process

Antibacterial wound dressing can benefit the wound healing by preventing bacterial infection, especially for the electrospun ones due to their porous structures and easily loading antibacterial drugs. However, it is challenging to apply the antibacterial electrospun wound dressing to covering the wound conveniently and safely. Here, we presented one step fabrication and application of antibacterial electrospun zein/cinnamon oil wound dressing via a handheld electrospinning setup. The prepared zein/cinnamon oil wound dressing showed gas permeability of (76.1±5.45) mm/s, hydrophilicity with zero body fluid contact angle, swelling stability after 24 h as well as antibacterial zones over 5 cm against both E. coli and S. aureus bacteria. Moreover, in situ electrospinning process can deposit the electrospun zein/cinnamon oil fibers directly onto the wound, meantime forming a wound dressing. The mice cut-wound model experiment demonstrated that the one step in situ fabrication and application of zein/cinnamon oil wound dressing could nearly heal the wound within 11 d.     

Preparation of Silver Nanoparticles Incorporated Electrospun Polyurethane Nano-fibrous Mat for Wound Dressing

Polyurethane foam is currently used as an exudate absorptive wound dressing material. In this study silver (Ag) nanoparticles were incorporated into electrospun polyurethane (PU) nanofiber to enhance the antibacterial as well as wound healing properties. The electrospinning parameters were optimized for PU with and without silver nanoparticles. Silver nanoparticles were synthesized by aqueous and organic methods. The water absorption, antibacterial and cytocompatibility of the PU-Ag nanofibers were studied and compared to that of conventional PU foam. The results indicated that the PU-Ag nanofibers could be used for wound dressing applications.     

Gamma Radiation‐Induced Crosslinked PVA/Chitosan Blends for Wound Dressing

Crosslinked polyvinyl alcohol (PVA) and chitosan polymer blends have been prepared by using gamma irradiation. Chitosan was used in the blends to prevent microbiological growth, such as bacteria and fungi on the polymer. The physical properties of the blend, such as gelation, water absorption, and mechanical properties were examined to evaluate the possibility of its application for wound dressing. A mixture of PVA/chitosan, with different ratios, were exposed to gamma irradiation doses of 20, 30, 50 KGy, to evaluate the effect of irradiation dose on the physical properties of the blend. It was found that the gel fraction increases with increasing irradiation dose and PVA concentration in the blend. Swelling percent increased as the composition of chitosan increased in the blend. The PVA/chitosan blend has a water content in the range between 40% and 60% and water absorption between 60% and 100%. The water vapor transmission rate value (WVRT) of the PVA/chitosan blend varies between 50% and 70%. The examination of the microbe penetration shows that the prepared blend can be considered as a good barrier against microbes. Thus, the PVA/chitosan blend showed satisfactory properties for use as a wound dressing.     

A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages

Wound dressings have experienced continuous and significant changes since the ancient times. The development starts with the use of natural materials to simply cover the wounds to the materials of the present time that could be specially made to exhibit various extraordinary functions. The modern bandage materials made of electrospun biopolymers contain various active compounds that are beneficial to the healing of wounds. These materials are fibrous in nature, with the size of fibers segments ranging from tens of nanometers to micrometers. With the right choices of biopolymers used for these fibrous materials, they could enhance the healing of wounds significantly compared with the conventional fibrous dressing materials, such as gauze. These bandages could be made such that they contain bioactive ingredients, such as antimicrobial, antibacterial, and anti‐inflammatory agents, which could be released to the wounds enhancing their healing. In an active wound dressing (AWD), the main purpose is to control the biochemical states of a wound in order to aid its healing process. This review provides an overview of different types of wounds, effective parameters in wound healing and different types of wound dressing materials with a special emphasis paid to those prepared by electrospinning. Copyright © 2009 John Wiley & Sons, Ltd.     

Acetate chitosan with CaCO3 doping form tough hydrogel for hemostasis and wound healing

In recent years, chitosan has been applied for wound management due to its properties of biocompatibility, biodegradability, antimicrobial activity, and low immunogenicity. But the poor water solubility in neutral pH limited its further application in clinical wound healing. To overcome this problem, acetate chitosan was developed and approved as commercial products for wound healing. However, the acidity of acetate chitosan was potentially allergenic, and the poor mechanical properties of its formed hydrogels also hindered the therapeutic efficacy in wound care. In this study, CaCO₃ was simply doped into acetate chitosan to form the wound dressing. After absorbing water, the H⁺ of acetate chitosan reacted with CaCO₃ to release Ca²⁺, resulting in acidity decreased. The production of Ca²⁺ and residue of CaCO₃ cross‐linked with chitosan to form a tough hydrogel by electrostatic interaction. The physical characteristics, swelling, mechanical testing, and blood clotting were evaluated. The results in vitro demonstrated that after doping CaCO₃ into acetate chitosan, the mechanical properties and blood clotting of the formed hydrogel were increased. Then, the evaluation of hydrogels in vivo revealed that it can also accelerate the wound healing by promoting re‐epithelization and collagen deposition. This simple way by doping CaCO₃ into acetate chitosan can increase wound healing, and it can also broad the application of acetate chitosan in clinical use.     

Irradiation of Crosslinked, Poly(Vinyl Alcohol) Blended Hydrogel for Wound Dressing

In order to obtain a more ideal hydrogel wound dressing, crosslinked hydrogel films blended with polyvinyl alcohol (PVA), polyvinyl pyrrolidone, kappa-carrageenan (KC), and powder silk were prepared by electron beam, and their physiochemical properties were investigated as a combination of function factors. The experimental results showed that the gel fraction of the hydrogel films depended mainly on irradiation dose and the monomer concentration of the polymers, the properties of hydrogel could be greatly extended or improved by blending homopolymers. The rate of gel formation of the hydrogel was raised, and the water evaporation from hydrogel could be retarded after mixing with KC, while the tensile strength of hydrogel films were obviously increased after mixing with silk. Toxicity and healing effect of PVA/PVP/KC/silk blended hydrogel films as wound dressings were evaluated. The irradiated blended hydrogel showed satisfactory properties for wound dressing, the hydrogel did not induceany acute general toxic effects, and it is effective for fast healing of wound.     

Preparation and Application of Quaternized Chitosan- and AgNPs-Base Synergistic Antibacterial Hydrogel for Burn Wound Healing

Infection is the major reason that people die from burns; however, traditional medical dressings such as gauze cannot restrain bacterial growth and enhance the healing process. Herein, an organic- and inorganic-base hydrogel with antibacterial activities was designed and prepared to treat burn wounds. Oxidized dextran (ODex) and adipic dihydrazide grafted hyaluronic acid (HA-ADH) were prepared, mixed with quaternized chitosan (HACC) and silver nanoparticles to fabricate Ag@ODex/HA-ADH/HACC hydrogel. The hydrogel, composed of nature biomaterials, has a good cytocompatibility and biodegradability. Moreover, the hydrogel has an excellent antibacterial ability and presents fast healing for burn wounds compared with commercial Ag dressings. The Ag@ODex/HA-ADH/HACC hydrogel will be a promising wound dressing to repair burn wounds and will significantly decrease the possibility of bacterial infection.     

Recent advances on herb‐derived constituents‐incorporated wound‐dressing materials: A review

Since ancient times, wound dressings have evolved with persistent and substantial changes. Several efforts have been made toward the development of new dressing materials, which can meet the demanding conditions for the treatment of skin wounds. Currently, many studies have been focused on the production and designing of herb‐incorporated wound dressings. Herb‐derived constituents are more effective than conventional medicines because of their nontoxic nature and can be administered over long periods. Herbal medicines in wound healing provide a suitable environment for aiding the natural course of healing. This review mainly focuses on the diverse approaches that have been developed to produce a wound dressing material, which can deliver herb‐derived bioactive constituents in a controlled manner. This review also discusses the common wound‐dressing materials available, basic principles of wound healing, and wound‐healing agents from medicinal plants.