In vitro and in vivo assays on egg white/polyvinyl alcohol/clay nanocomposite hydrogel wound dressings

Novel nanocomposite hydrogel wound dressings on the basis of egg white and polyvinyl alcohol, as matrix, and natural Na-montmorillonite clay, as reinforcing agent, were prepared and their performances on wound healing investigated in vitro and in vivo. In vitro cytotoxicity assay revealed non-cytotoxic activity and excellent biocompatibility level of prepared nanocomposite hydrogel wound dressings. The bacterial penetration assay showed the prepared nanocomposite hydrogel wound dressings are excellent barriers against microorganisms and could protect the wound from infection during the wound healing. In vivo animal study showed that the wound healing process was considerably faster in wounds covered with nanocomposite hydrogel wound dressings compared to the conventional wound dressing, i.e. sterile gauze, due to creation of a moist environment on the wound surface and faster migration rate of the epidermal cells. The mechanical properties of healed wounds with nanocomposite hydrogel wound dressings were better than those control wounds covered with sterile gauze due to their better collagen formation ability as a result of created moist healing condition as well as the presence of egg white, as a source of proteins, in their structures.     

Development of a complex hydrogel of hyaluronan and PVA embedded with silver nanoparticles and its facile studies on Escherichia coli

Novel nanocomposite hydrogels composed of hyaluronan (HA), poly(vinyl alcohol) (PVA) and silver nanoparticles were prepared by several cycles of freezing and thawing. The nanocomposite was then characterised using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), wide-angle X-ray diffraction (XRD) and scanning electron microscopy (SEM). The complex hydrogels consisted of semi-interpenetrating network structures, with PVA microcrystallines as junction zones. By increasing the HA content, the crystallinity and melting temperature of the complex hydrogels decreased, whereas the glass transition temperatures of these materials increased because of the steric hindrance of HA and the occurrence of intermolecular interactions through hydrogen bonding between HA and PVA in the complex hydrogels. Swelling studies showed that in comparison with the swelling properties of the cryogels from PVA alone, those of the complex hydrogels can be significantly improved and presented in a pH-sensitive manner. In addition, silver nanoparticles were synthesised through UV-initiated photoreduction with HA functioning as a reducing agent and stabiliser. The silver nanoparticles were then incorporated in situ into the HA/PVA complex hydrogel matrix. The size and morphology of the as-prepared Ag nanoparticles were investigated through ultraviolet–visible light spectroscopy, transmission electron microscopy, XRD and thermogravimetric analysis. The experimental results indicated that silver nanoparticles 20–50?nm in size were uniformly dispersed in the hydrogel matrix. The antibacterial effects of the HA/PVA/Ag nanocomposite hydrogel against Escherichia coli were evaluated. The results show that this nanocomposite hydrogel possesses high antibacterial property and has a potential application as a wound dressing material.     

Polyurethane based hybrid ciprofloxacin-releasing wound dressings designed for skin engineering purpose

PurposeEven in the 21st century, chronic wounds still pose a major challenge due to potentially inappropriate treatment options, so the latest wound dressings are hybrid systems that enable clinical management, such as a hybrid of hydrogels, antibiotics and polymers. These wound dressings are mainly used for chronic and complex wounds, which can easily be infected by bacteria.Materials and methodsSix Composite Porous Matrices (CPMs) based on polyurethane (PUR) in alliance with polylactide (PLAs) and poly(vinyl alcohol) (PVA) were prepared and analyzed using optical microscopy. Three different types of hydrogels and their Ciprofloxacin (Cipro) modified variants’ ratios were prepared and analyzed using FTIR, SEM and EDX techniques. Six Hybrid Cipro-Releasing Hydrogel Wound Dressings (H-CRWDs) were also prepared and underwent short-term degradation, Cipro release, microbiology and cell viability measurements.ResultsAverage porosity of CPMs was in the range of 69–81%. The pore size of the obtained CPMs was optimal for skin regeneration. Short-term degradation studies revealed degradability in physiological conditions regardless of sample type. A meaningful release was also observed even in short time (21.76 ?± ?0.64 ?μg/mL after 15 ?min). Microbiological tests showed visible inhibition zones. Cell viability tests proved that the obtained H-CRWDs were biocompatible (over 85% of cells).ConclusionsA promising hybrid wound dressing was labeled. Simple and cost-effective methods were used to obtain microbiologically active and biocompatible dressings. The results were of importance for the design and development of acceptable solutions in the management of chronic wounds of high potential for infection.     

Preparation of sponge-like macroporous PVA hydrogels via n-HA enhanced phase separation and their potential as wound dressing

Polyvinyl alcohol (PVA) hydrogels have been widely studied for biomedical applications due to their water solubility, non-toxicity, non-carcinogenicity, and biocompatibility. However, PVA hydrogels prepared by the physical crosslinking method usually do not exhibit a macroporous structure, which limits their application when PVA hydrogels are used alone as a wound dressing. Here, we reported a sponge-like macroporous PVA hydrogel (SPH) prepared by employing polyethylene glycol and nano-hydroxyapatite (n-HA) to enhance phase separation. After being fabricated through cyclic freezing/thawing, the resulting PVA hydrogels possessed macroporous structures. The swelling ratio could reach nearly 1500%, resulting from the excellent water absorption capacity, and the sample could rapidly restore to the original state after being pressed, suggesting a sponge-like characteristic. Furthermore, cell experiments showed that macroporous PVA hydrogels exhibited good biocompatibility and the results of wound closure and H&E analysis consistently indicated that SPHs could significantly promote the wound healing process.     

Facile and large-scale synthesis of curcumin/PVA hydrogel: effectively kill bacteria and accelerate cutaneous wound healing in the rat

The complicated synthesis procedure and limited preparation size of hydrogel inhibit its clinical application. Therefore, a facile preparation method for large-size hydrogel is required. In this study, a series of curcumin (Cur)/polyvinyl alcohol (PVA) hydrogel in a large size with different Cur concentrations is prepared by a facile physical-chemical crosslinking. The physicochemical properties, antibacterial performance and accelerating wound healing ability are evaluated with the aim of attaining a novel and effective wound dressing. The results show that the as-prepared hydrogel with the optimal Cur to PVA volume ratio of 1:5 (20% Cur/PVA) exhibits the best antibacterial abilities to E. coli (85.6%) and S. aureus (97%) than other hydrogels. When the volume ratio of Cur to PVA is 1:10 (10% Cur/PVA), the hydrogel can significantly accelerate the wound healing in rats, and successfully reconstruct intact and thickened epidermis during 14 day of healing of impaired wounds after histological examination. In one word, the present approach can shed new light on designing new type of hydrogels with promising applications in wound dressing.     

Investigation of lysine acrylate containing poly(N-isopropylacrylamide) hydrogels as wound dressings in normal and infected wounds

The design of materials for cutaneous wound dressings has advanced from passive wound covers to bioactive materials that promote skin regeneration and prevent infection. Crosslinked poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogels have been investigated for a number of biomedical applications. While these materials can be used for drug delivery, limited cell interactions restrict their biological activity. In this article, acryoyl-lysine (A-Lys) was incorporated into poly(ethylene glycol) crosslinked PNIPAAm to enhance biological activity. A-Lys could be incorporated into the hydrogels to improve cellular interaction in vitro, while maintaining swelling properties and thermoresponsive behavior. Polyhexamethylene biguanide, an antimicrobial agent, could be encapsulated and released from the hydrogels and resulted in decreased bacteria counts within 2 hours. Two in vivo animal wound models were used to evaluate the hydrogel wound dressing. First, application of the hydrogels to a rodent cutaneous wound healing model resulted in significant increase in healing rate when compared with controls. Moreover, the hydrogels were also able to decrease bacteria levels in an infected wound model. These results suggest that PNIPAAm hydrogels containing A-Lys are promising wound dressings due to their ability to promote healing and deliver active antimicrobial drugs to inhibit infection.     

In Vivo and Cytotoxic Assays of a Poly(vinyl alcohol)/Clay Nanocomposite Hydrogel Wound Dressing

In the present work, a nanocomposite hydrogel wound dressing was prepared on the basis of poly(vinyl alcohol) using organically-modified montmorillonite as nanoclay by the freezing–thawing cyclic method. In vivo assays were performed to evaluate its performance as an applicable wound dressing on animals. It showed an improved healing process for wounds covered by the prepared nanocomposite hydrogel compared with control wounds covered by sterile gauze. Significant improvements, such as better creation of moist surfaces on the wound with less scar formation, shorter duration of healing operation and better closing of the wound edges with enhanced tensile properties of the healed wound, i.e., tensile strength and elongation-at-break, were observed using the prepared nanocomposite hydrogel in comparison to the sterile gauze. An in vitro cytotoxic assay was also utilized to determine the biocompatibility of the prepared nanocomposite hydrogel. It showed that the prepared nanocomposite hydrogel is non-toxic and can be used as a biocompatible wound dressing in practical wound management.     

Electrospun polyvinyl alcohol-polyvinyl pyrrolidone nanofibrous membranes for interactive wound dressing application

Cross-linked polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) composite nanofibrous membranes have been prepared by electrospinning. Mechanical properties of the membranes improved significantly with PVP addition. PVP improved hydrophilicity and sustainable degradation of the membranes. Biocompatibility of the membranes was assessed by in vitro culture of native skin cells (L929 fibroblast and HaCaT keratinocytes). Tests showed sustained release of the antibiotic ciprofloxacin hydrochloride monohydrate by the membranes. Further, zone of inhibition study against Staphylococcus aureus growth demonstrated protective action against external pathogenic microbes. These studies show these simple PVA–PVP nanofibrous membranes are promising interactive antibiotic-eluting wound dressing materials.     

Wound healing properties of PVA/starch/chitosan hydrogel membranes with nano Zinc oxide as antibacterial wound dressing material

In this work, hydrogel membranes were developed based on poly vinyl alcohol (PVA), starch (St), and chitosan (Cs) hydrogels with nano Zinc oxide (nZnO). PVA/St/Cs/nZnO hydrogel membranes were prepared by freezing-thawing cycles, and the aqueous PVA/St solutions were prepared by dissolving PVA in distilled water. After the dissolution of PVA, starch was mixed, and the mixture was stirred. Then, chitosan powder was added into acetic acid, and the mixture was stirred to form a chitosan solution. Subsequently, Cs, St and PVA solutions were blended together to form a homogeneous PVA/St/Cs ternary blend solution. Measurement of Equilibrium Swelling Ratio (ESR), Water Vapor Transmission Test (WVTR), mechanical properties, scanning electron microscopy (SEM), MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay, antibacterial studies, in vivo wound healing effect and histopathology of the hydrogel membranes were then performed. The examination revealed that the hydrogel membranes were more effective as a wound dressing in the early stages of wound healing and that the gel could be used in topic applications requiring a large spectrum of antibacterial activity; namely, as a bandage for wound dressing.     

In Vitro Biocompatibility of New PVA-Based Hydrogels as Vitreous Body Substitutes

In order to synthesize injectable hydrogels suitable as vitreous body substitutes, a new method based on the use of trisodium trimetaphosphate (STMP) to cross-link PVA was recently proposed. Hydrogels with different molar ratios between STMP and PVA were realised. The aim of the present study was the evaluation of the biocompatibility of the different STMP/PVA hydrogels synthesised by analysing the effects of their in vitro interaction with cultures of mouse fibroblasts NIH3T3, primary human microvascular endothelial cells adult (HMVECad) and human lens cells. Cytotoxicity of hydrogels was first evaluated by analysing cell density and proliferation. Morphological and morphometric analysis of cell in contact with hydrogels was then performed using light microscopy and scanning electron microscopy, respectively. Moreover, cell adhesion and growth onto the hydrogels surface was evaluated and correlated to the amount of adsorbed proteins. At last, the biocompatibility of the sheared STMP/PVA 1:8 hydrogel was tested. The in vitro data of all the STMP/PVA hydrogels demonstrated their good biocompatibility, and indicated that the 1:8 sample was the most promising as vitreous body substitute.     

Genipin-crosslinked polyvinyl alcohol/silk fibroin/nano-hydroxyapatite hydrogel for fabrication of artificial cornea scaffolds—a novel approach to corneal tissue engineering

Abstract

Design of artificial corneal scaffolds substitute is crucial for replacement of impaired cornea. In this paper, porous polyvinyl alcohol/silk fibroin/nano-hydroxyapatite (PVA/SF/n-HA) composite hydrogel was prepared via the genipin (GP) cross-linking, the pore diameter of the hydrogel ranged from 8.138?nm and 90.269?nm, and the physical and physiological function of hydrogel were investigated. The resulting hydrogel exhibited favourable physical properties. With the GP content increasing, the structural regularity of PVA/SF/n-HA composite hydrogel was enhanced and the thermal stability was improved. The moisture content was slightly decreased and generally maintained at approximately 70%. The tensile strength was heightened up to 0.64?MPa, while the breaking elongation was decreased slightly. Moreover, the biofunction was investigated. The in vitro degradation test demonstrated that with the addition of GP, the stability of the composite hydrogels in protease XIV solution was promoted and the three-dimensional porosity structure of composite hydrogels was maintained as ever. And the human corneal fibroblasts (HCFs) were employed to examine the cells cytotoxicity of the PVA/SF/n-HA composite hydrogels with different GP content by CCK-8 assay. Based on confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM), HCFs had individually commendable adhesion and proliferation on PVA/n-HA/SF composite hydrogel. HCFs proliferated and grew into the pores of composite hydrogel. The results of biocompatibility experiments of composite hydrogel suggested that it was no acute toxicity, in vitro cytotoxicity was 0 or 1 grade. Overall, results from this paper, PVA/n-HA/SF composite hydrogel was a qualified medical material which conformed to the national standard, could be a promising alternative for artificial cornea scaffold material—a novel approach to corneal tissue engineering.     

Self‐Healable and Conductive Double‐Network Hydrogels with Bioactive Properties

Nanocomposite hydrogels are a class of materials that are generally composed of hydrophilic polymers and nanofillers. They can have various important properties such as self‐healing, conductivity, toughness, bioactivity, facile processing ability, and this enables manifold practical applications. However, development of a single nanocomposite hydrogel with all of the properties of interest is yet to be realized. Here, a double‐network (DN) polymer hydrogel consisting of poly(vinyl alcohol)‐poly(sodium 4‐styrene sulfonate)‐poly(2‐aminoethylenemethacrylate) polymers (PVA‐P(NaSS)‐P(AEMA)) is reported. The obtained DN hydrogels containing copper ions, (PVA‐P(NaSS)‐P(AEMA)@Cu²⁺) hydrogel and copper nanoparticles (PVA‐P(NaSS)‐P(AEMA)@Cu) hydrogels, are found to exhibit self‐healing, conducting, high mechanical, bioactive, and wound healing properties. The fabricated hydrogel may potentially be applied in the biomedical and electronics sector.     

Polyvinyl pyrrolidone/carrageenan blend hydrogels with nanosilver prepared by gamma radiation for use as an antimicrobial wound dressing

Hydrogels were prepared using polyvinyl pyrrolidone (PVP) blended with carrageenan by gamma irradiation at different doses of 25 and 40 kGy. Gel fraction of hydrogels prepared using 10 and 15% PVP in combination with 0.25 and 0.5% carrageenan was evaluated. Based on gel fraction, 15% PVP in combination with 0.25% carrageenan and radiation dose of 25 kGy was selected for the preparation of hydrogels with nanosilver. Radiolytic synthesis of silver nanoparticles within the PVP hydrogel was carried out. The hydrogels with silver nanoparticles were assessed for antimicrobial effectiveness and physical properties of relevance to clinical performance. Fluid handling capacity (FHC) for PVP/carrageenan was 2.35 ± 0.39–6.63 ± 0.63 g/10 cm² in 2–24 h. No counts for Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans were observed in the presence of hydrogels containing 100 ppm nanosilver after 3–6 h. The release of silver from hydrogels containing 100 ppm nanosilver was 20.42 ± 1.98 ppm/100 cm² in 24 h. Hydrogels containing 100 ppm nanosilver with efficient FHC demonstrated potential microbicidal activity (≥3 log₁₀ decrease in CFU/ml) against wound pathogens, P. aeruginosa, S. aureus, E. coli, and C. albicans. PVP/carrageenan hydrogels containing silver nanoparticles can be used as wound dressings to control infection and facilitate the healing process for burns and other skin injuries.     

Time-Dependent Alginate/Polyvinyl Alcohol Hydrogels as Injectable Cell Carriers

Alginate hydrogels have been widely utilized as cell carriers due to their simplicity for fabricating cell-immobilized gel beads or 3-dimentional porous scaffolds, biocompatibility and non-toxicity to cells. Generally alginate hydrogels have been produced by contacting alginate solution with CaCl₂ as a cross-linking agent. However, the major disadvantages of this system are that the gelation rate is too fast and hard to control, and the prepared alginate gels cannot be injected. Injectable alginates have been prepared by using CaSO₄ or CaCO₃ as a cross-linking agent. However, the gelation rate of alginate with CaCO₃ is slow owing to the low solubility of CaCO₃ in water, while that with CaSO₄ is too fast to form uniform gels. In this study, we prepared injectable alginate/polyvinyl alcohol (PVA) blend hydrogels with controllable gelation rate by using CaSO₄ as a cross-linking agent and Na₂HPO₄ as a cross-linking retardation agent. The gelation rate could be controlled by adjusting CaSO₄/Na₂HPO₄ ratio in the solution. The alginate and PVA showed good compatibility in aqueous solutions or gels. The gelation rate of alginate increased with increasing Na₂HPO₄ and decreasing CaSO₄ concentrations, as expected. The PVA itself in the alginate/PVA blend did not affect the gelation rate. All alginate/PVA hydrogels demonstrated some extraction of PVA, but the extraction extent was not much even after 7 days immersion in water. The alginate/PVA hydrogels were examined for their in vitro cell compatibility by the culture of chondrocytes (human chondrocyte cell line) in the gels up to 28 days. The cells were grown almost linearly in the alginate/PVA hydrogels with higher PVA compositions showing better cell growth. The GAG contents from the cells in the hydrogels did not show dramatic changes with culture time, however, they also increased gradually in the alginate/PVA hydrogels with higher PVA composition. The PVA in the hydrogels seemed to play positive roles for the growth and activity of chondrocytes. The alginate/PVA hydrogels with controllable gelation rate are expected to be applicable as injectable cell carriers.     

Temperature-sensitive PVA/PNIPAAm semi-IPN hydrogels with enhanced responsive properties

A series of temperature-sensitive hydrogels of semi-interpenetrating polymeric networks (semi-IPN) composed of poly(N-isopropylacrylamide) (PNIPAAm) and poly(vinyl alcohol) (PVA) were prepared by radical polymerization. The PNIPAAm networks were cross-linked by N,N'-methylenebisacrylamide in the presence of linear PVA. The reaction processes were investigated by rheometry using oscillatory deformation tests. It was found that gelations were very fast and the modulus reached equilibrium within about 12.5min. The prepared semi-IPN hydrogels were characterized for their morphologies and thermal behaviors by scanning electron microscopy and differential scanning calorimetry, respectively. The interior network structures of the semi-IPN matrix became more porous with increasing PVA. In comparison to the conventional PNIPAAm gel, the newly reported semi-IPN hydrogels exhibited the same lower critical solution temperature. Their swelling properties, such as temperature dependence of equilibrium swelling ratio, shrinking kinetics and reswelling kinetics in water, were also studied. Experimental data indicated that the shrinking and reswelling rates of the semi-IPN hydrogels were much faster than those of the conventional PNIPAAm hydrogels. With this novel approach, water absorption and response properties could be adjusted by tuning the feed ratio of NIPAAm and PVA. These fast responsive hydrogels exhibited improved temperature sensitivity and swelling properties compared to the conventional PNIPAAm hydrogel, which would be critical and desirable for a gel to find potential applications in biomedical fields, such as drug delivery systems and sensors.     

Fabrication and characterization of hydroxypropyl guar-poly (vinyl alcohol)-nano hydroxyapatite composite hydrogels for bone tissue engineering

Abstract

Biocompatible bone implants composed of natural materials are highly desirable in orthopedic reconstruction procedures. In this study, novel and ecofriendly bionanocomposite hydrogels were synthesized using a blend of hydroxypropyl guar (HPG), poly vinyl alcohol (PVA), and nano-hydroxyapatite (n-HA) under freeze-thaw and mild reaction conditions. The hydrogel materials were characterized using various techniques. TGA studies indicate that both composites, HPG/PVA and HPG/PVA/n-HA, have higher thermal stability compared to HPG alone whereas HPG/PVA/n-HA shows higher stability compared to PVA alone. The HPG/PVA hydrogel shows porous morphology as revealed by the SEM, which is suitable for bone tissue regeneration. Additionally, the hydrogels were found to be transparent and flexible in nature. In vitro biomineralization study performed in simulated body fluid shows HPG/PVA/n-HA has an apatite like structure. The hydrogel materials were employed as extracellular matrices for biocompatibility studies. In vitro cell viability studies using mouse osteoblast MC3T3 cells were performed by MTT, Trypan blue exclusion, and ethidium bromide/acridine orange staining methods. The cell viability studies reveal that composite materials support cell growth and do not show any signs of cytotoxicity compared to pristine PVA. Osteoblastic activity was confirmed by an increased alkaline phosphatase enzyme activity in MC3T3 bone cells grown on composite hydrogel matrices.     

Electrospun mupirocin loaded polyurethane fiber mats for anti-infection burn wound dressing application

Wound care treatment is a serious issue faced by the medical staffs due to its variety and complexity. Wound dressings are typically used to manage the various types of wounds. In this study, polyurethane (PU) fibers containing mupirocin (Mu), a commonly used antibiotic in wound care, were fabricated via electrospinning technique. The aim of this study was to develop biomedical electrospun fiber scaffolds for preventing wound infections with good compatibility and to demonstrate their applications as anti-infective burn wound dressings. The surface morphology of fibers was obtained by scanning electron microscopy. FT-IR spectra, water vapor transmission rate, and drug release study in vitro were tested to demonstrate the fiber scaffold characteristic. The prepared PU/Mu composite scaffolds had satisfactory antibacterial activity especially against Staphylococcus aureus. The cell studies revealed that the scaffolds were biocompatible and safe for cell attachment. Histological and immunohistochemical examinations were performed in rats, and the results indicated the histological analysis of tissue stained with H&E showed no obvious inflammation reaction. The results indicated that the electrospun scaffolds were capable of loading and delivering drugs, and could be potentially used as novel antibacterial burn wound dressings.     

Anisotropic polyvinyl alcohol hydrogel for cardiovascular applications

Polyvinyl alcohol (PVA) is a hydrophilic polymer with various characteristics desired for biomedical applications and can be transformed into a solid hydrogel by physical crosslinking, using a low-temperature thermal cycling process. As with most polymeric materials, the mechanical properties of the resultant PVA are isotropic, as oppose to most soft tissues, which are anisotropic. The objective of this research is to develop a PVA-based hydrogel that not only mimics the nonlinear mechanical properties displayed by cardiovascular tissues, but also their anisotropic behavior. By applying a controlled strain to the PVA samples, while undergoing low-temperature thermal cycling, we were able to create oriented mechanical properties in PVA hydrogels. The oriented stress-strain properties of porcine aorta were matched simultaneously by a PVA hydrogel prepared (10% PVA, cycle 3, 75% initial strain). This novel technique allows the controlled introduction of anisotropy to PVA hydrogel, and gives a broad range of control of its mechanical properties, for specific medical device applications.     

Development of a Wound Dressing Composed of Hyaluronic Acid and Collagen Sponge with Epidermal Growth Factor

This study was designed to investigate the effect of a wound dressing composed of hyaluronic acid (HA) and collagen (Col) sponge containing epidermal growth factor (EGF) on various parameters of wound healing in vitro and in vivo. High-molecular-weight (HMW) HA solution, hydrolyzed low-molecular-weight (LMW) HA solution and heat-denatured Col solution were mixed, followed by freeze-drying to obtain a spongy sheet. Cross-linkage between Col molecules was induced by UV irradiation to the spongy sheet (Type-I dressing). In a similar manner, a spongy sheet containing EGF was prepared (Type-II dressing). The efficacy of these products was firstly evaluated in vitro. Fibroblast proliferation was assessed in culture medium in the presence or absence of a piece of each wound dressing. EGF stimulated cell proliferation after UV irradiation and dry sterilization at 110°C for 1 h. In the second experiment, fibroblasts-embedded Col gels were elevated to the air–liquid interface to create a wound surface model, on which wound dressings were placed and cultured for 1 week. Cell proliferation and the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were investigated. With Type-II dressings, the amounts of VEGF and HGF released from fibroblasts in the Col gel were significantly increased compared with Type-I dressing. Next, the efficacy of these products was evaluated in vivo using Sprague–Dawley (SD) rats. Wound conditions after 1 and 2 weeks of treatment with the wound dressings were evaluated based on the gross and histological appearances. Type-II dressings promoted a decrease in wound size, re-epithelialization and granulation tissue formation associated with angiogenesis. These findings indicate that the combination of HA, Col and EGF promotes wound healing by stimulating fibroblast function.     

Evaluation of a Wound Dressing Composed of Hyaluronic Acid and Collagen Sponge Containing Epidermal Growth Factor in Diabetic Mice

Abstract

This study investigated the effect of a wound dressing composed of hyaluronic acid (HA) and collagen (Col) sponge containing epidermal growth factor (EGF) on wound healing in diabetic mice. High-molecular-weight (HMW) HA aqueous solution, hydrolyzed low-molecular-weight (LMW) HA aqueous solution and heat-denatured Col aqueous solution were mixed, followed by freeze-drying to obtain a spongy sheet. Cross-linkage between Col molecules was induced by UV irradiation to the spongy sheet (Type-I wound dressing). In a similar manner, a spongy sheet containing EGF (Type-II wound dressing) was prepared by freeze-drying the mixed solution of HMW-HA, LMW-HA and Col containing EGF. The efficacy of these products was evaluated in type-II diabetic BKS.Cg-+Lepr^db/+Lepr^db (db/db) mice. Wound dressings were applied to a full-thickness, dorsal skin defect measuring 1.5 cm × 2.0 cm, showing adipose tissue. In the control group, a commercially available artificial dermis composed of collagen spongy sheet (TERUDERMIS^®) was used. A commercially available polyurethane film dressing (Bioclusive^®) was applied over each wound dressing. After 1 week of application, wound conditions were evaluated based on their gross and histological appearances. Type-I and -II wound dressings promoted a decrease in wound size associated with angiogenesis and granulation tissue formation, compared with the artificial dermis. In particular, Type-II wound dressings promoted sufficient re-epithelialization. These findings indicate that the combination of HA, Col and EGF promotes wound healing by stimulating cell activity including cell migration and proliferation on the adipose tissue in a diabetic wound. Type-I and -II wound dressings would be useful to prepare a well-vascularized wound bed acceptable for split-thickness auto-skin grafting.