Silicone-coated non-woven polyester dressing enhances reepithelialisation in a sheep model of dermal wounds

Negative-pressure wound therapy (NPWT) also known as V.A.C.?(Vacuum-assisted closure), is widely used to manage various type of wounds and accelerate healing. NPWT has so far been delivered mainly via open-cell polyurethane (PU) foam or medical gauze. In this study an experimental setup of sheep wound model was used to evaluate, under NPWT conditions, the performance of a silicone-coated non-woven polyester (N-WPE) compared with PU foam and cotton hydrophilic gauze, used as reference materials. Animals were anesthetized with spontaneous breathing to create three 3?×?3?cm skin defects bilaterally; each animal received three different samples on each side (n?=?6 in each experimental group) and was subjected to negative and continuous 125?mmHg pressure up to 16?days. Wound conditions after 1, 8 and 16?days of treatment with the wound dressings were evaluated based on gross and histological appearances. Skin defects treated with the silicone-coated N-WPE showed a significant decrease in wound size, an increase of re-epithelialization, collagen deposition and wound neovascularisation, and a minimal stickiness to the wound tissue, in comparison with gauze and PU foam. Taken all together these findings indicate that the silicone-coated N-WPE dressing enhances wound healing since stimulates higher granulation tissue formation and causes minor tissue trauma during dressing changes.     

Hydroxyapatite porous scaffold engineered with biological polymer hybrid coating for antibiotic Vancomycin release

The purpose of this study is to improve hydroxyapatite (HA) porous scaffolds via coating with biological polymer-HA hybrids for use as wound healing and tissue regeneration. Highly porous HA scaffolds, fabricated by a polyurethane foam reticulate method, were coated with hybrid coating solution, consisting of poly(-caprolactone) (PCL), HA powders, and the antibiotic Vancomycin. The PCL to HA ratio was fixed at 1.5 and the drug amounts were varied [drug/(PCL + HA) = 0.02 and 0.04]. For the purpose of comparison, bare HA scaffold without the hybrid coating layer was also loaded with Vancomycin via an immersion-adsorption method. The hybrid coating structure and morphology were observed with Fourier transformed infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The effects of the hybrid coating on the compressive mechanical properties and the in vitro drug release of the scaffolds were investigated in comparison with bare HA scaffold. The PCL-HA hybrid coating altered the scaffold pore structure slightly, resulting in thicker stems and reduced porosity. With the hybrid coating, the HA scaffold responded to an applied compressive stress more effectively without showing a brittle failure. This was attributed to the shielding and covering of the framework surface by the coating layer. The encapsulated drugs within the coated scaffold was released in a highly sustained manner as compared to the rapid release of drugs directly adsorbed on the pure HA scaffold. These findings suggest that the coated HA scaffolds expand their applicability in hard tissue regeneration and wound healing substitutes delivering bioactive molecules.     

Studies on gelatin-based sponges. Part III: A comparative study of cross-linked gelatin/alginate, gelatin/hyaluronate and chitosan/hyaluronate sponges and their application as a wound dressing in full-thickness skin defect of rat

Novel cross-linked sponges composed of gelatin/alginate and gelatin/hyaluronate and chitosan/hyaluronate (GH, GA and CH, respectively) were prepared and compared. Six different sponges with or without silver sulfadiazine (AgSD) were applied on the full-thickness dorsal skin defect of Wistar rat. The histology and epidermal wound healing rates of the skin defects were investigated by light microscopy and computerized morphometry 5 and 12 days post-operatively. In our full-thickness wound model (diameter 1 cm), the AgSD-impregnated sponges showed good wound healing performances on the whole. However, there appeared meaningful differences of wound healing between the gelatin-based sponges (GH, GA) and the CH. GH with AgSD was found to show the best wound healing properties as a wound dressing resulting from histological findings and computerized morphometric analysis of epidermal healing.     

In vitro evaluation of biocompatibility of different wound dressing materials

The in vitro biocompatibility of newly developed wound dressings consisting of different chitosan salts (chitosan lactate, glutamate and chloride) and a chitosan derivative (methylpyroolidinone chitosan) was compared with three commercially available wound dressings made of collagen, calciumalginate, and gelatin, by evaluation in a fibroblast cell culture system. Three experimental models which reflect relevant stages of wound healing were used, and the significant influence of the experimental setting on the results was demonstrated. Collagen and methylpyrrolidinone chitosan were the most compatible materials under the investigated test conditions. Chitosan chloride and glutamate were the least compatible substances. The results indicated that wound dressings made of chitosan lactate and methylpyrrolidinone chitosan as well as the three commercially available dressings are well tolerated.     

Silver sulfadiazine loaded chitosan/chondroitin sulfate films for a potential wound dressing application

Silver sulfadiazine (AgSD) loaded chitosan/chondroitin sulfate (CHI/CS) films were formed to be applied as a potential wound dressing material. The liquid uptake capacity of both, CHI/CS and CHI/CS/AgSD, films exhibited a pH-dependent behavior. Tensile tests showed that the amount of CS used to form the films and the further incorporation of AgSD affect the mechanical properties of the films. In vitro AgSD-release assays showed that the CHI/CS mass ratio influences the AgSD release rate. All the investigated CHI/CS/AgSD films sustain the AgSD release up to 96 h at physiological pH. Antibacterial activity and cell viability assays showed that all the CHI/CS/AgSD films have activity against Pseudomonas aeruginosa and Staphylococcus aureus but they were not toxic to Vero cells. The results presented in this work indicate that the CHI/CS/AgSD exhibits potential to be applied as a wound dressing material.     

Hyaluronic acid/mildly crosslinked alginate hydrogel as an injectable tissue adhesion barrier

Although hyaluronic acid (HA) has been conventionally utilized as a tissue adhesion barrier material, its rapid clearance in the body still remains as a big challenge in the clinical practice. In this study, we prepared a hydrogel of HA embedded in mildly crosslinked alginate (HA/mcALG hydrogel), which is injectable, easily covers injured tissues, and remains stably at the applied site during wound healing (by muco-adhesive HA embedded in the network structure of the mcALG hydrogel). The HA/mcALG hydrogel was highly effective for the prevention of peritoneal tissue adhesion compared to HA and mcALG hydrogels, and did not lead to any abnormal tissue responses during wound healing. The HA/mcALG hydrogel can be a good candidate as an injectable tissue adhesion barrier for clinical applications.     

An All-in-One “4A Hydrogel”: through First-Aid Hemostatic,Antibacterial, Antioxidant,and Angiogenic to Promoting Infected Wound Healing

Currently used wound dressings are ineffective. Hence, there is a need to develop introduce a high-performance medicament with multiple functions including rapid hemostasis and excellent antibacterial activity to meet the growing worldwide demand for wound healing products. Here, inspired by the strong adhesion of mussels and the enzyme-mimicking activity of nanometallic biomaterials, the authors developed an injectable hydrogel to overcome multiple limitations of current wound dressings. The hydrogel is synthesized via esterification reaction between poly(vinyl alcohol) (PVA) and 3,4-dihydroxyphenylalanine (DOPA), followed by catechol-metal coordination between Cu²⁺ and the catechol groups of DOPA to form a PVA-DOPA-Cu (PDPC) hydrogel. The PDPC hydrogel possesses excellent tissue adhesive, antioxidative, photothermal, antibacterial, and hemostatic properties. The hydrogel rapidly and efficiently stopped bleeding under different traumatic conditions, including otherwise-lethal liver injury, high-pressure carotid artery rupture, and even fatal cardiac penetration injuries in animal models. Furthermore, it is demonstrated that the PDPC hydrogel affected high-performance wound repair and tissue regeneration by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. The results show that PDPC hydrogel is a promising candidate for rapid hemorrhage control and efficient wound healing in multiple clinical applications.     

Antimicrobial and release study of drug loaded PVA/PEO/CMC wound dressings

The aim of the present study was to develop PVA/PEO/CMC/aloe vera (PPCAV) and PVA/PEO/CMC/curcumin (PPCCu) dressings with nonwoven polyester fabric as the support layer via freeze-drying (FD) approach. Tetracycline hydrochloride drug (TC) was loaded along with curcumin and aloe vera on these dressings. The morphology of the dressings was characterized by scanning electron microscopy. The swelling behavior, water vapor transmission rate (WVTR), in vitro drug release and antimicrobial nature were analyzed to assess the applicability of these freeze-dried membranes as wound dressing materials. The results show that these dressings made from PPCAVTC and PPCCuTC were highly porous with three-dimensional interconnected porous morphology. The cumulative release of drug from the dressings increases with increasing immersion time and continued up to 24 h, after that it gets leveled off. These dressings evidenced wonderful antimicrobial nature in vitro. These dressings were found to have more than 900 % PBS uptake, WVTR was found to be in the range 2,000–2,500 gm^?2 day^?1. These dressings possess many characteristics desirable in an ideal wound dressing material.     

Asymmetric polyurethane membrane with inflammation-responsive antibacterial activity for potential wound dressing application

By combining solvent evaporation with wet phase inversion technique, an asymmetric polyurethane membrane (ASPU) was constructed from a sulfanilamide-conjugated PU, as a potential candidate for wound dressing application. As a result of the combined membrane-formation method, the ASPU membrane was constituted by an integral and dense skin layer supported by a porous sublayer. The skin layer was found impermeable to pathogenic organisms, while the sublayer was intended for draining excessive exudates. Compared with typical PU membrane dressings commercially available, the ASPU membrane exhibited a reasonable moisture vapor transmission rate, as well as significantly improved gas circulation and exudate absorption capabilities, which synergistically optimized the wound microenvironment for proper healing. Furthermore, the sulfanilamide-conjugated PU constituting ASPU membrane was designed as susceptible to urease, a representative hydrolase derived from inflammation-causing pathogens. In the presence of urease, urea linkages adjacent to sulfanilamide monomeric units were found catalytically cleaved, enabling release of free antibiotic sulfanilamide that held pharmacological activity from ASPU membrane. When incubated without urease, those cleavage sites exhibited substantially high resistance against hydrolysis so that no sulfanilamide release was detected throughout the incubation period. In this inflammation-responsive manner, the anti-inflammatory efficiency of antibiotics was significantly enhanced, while undesirable side effects associated with antibiotic abuse was minimized. Cell culture assay further revealed that the ASPU membrane displayed no cytotoxicity toward normal human dermis fibroblasts, suggesting a biocompatible potential. Based on these results, the multifunctional ASPU membrane designed in this study might be clinically suitable as an ideal biomedical dressing for wound care.     

Electrospun polyvinylidene pyrolidone/gelatin membrane impregnated with silver sulfadiazine as wound dressing for burn treatment

Nanofibrous membranes used for burn treatment have become widely popular due to their large surface area and high porous structure. In this study, electrospinning was used to fabricate a blended nanofibrous membrane of polyvinylidene pyrolidone (PVP) and gelatin, to use as wound dressing. The physical and mechanical properties of this novel membrane were investigated using SEM, FTIR and tensile tests. Results showed that poor mechanical properties of gelatin, which are preferred in medical applications for curing burns as they allow for antigen activity and skin repair, can be enhanced by adding PVP in the solution. Silver sulfadiazine (AgSD), an antibacterial agent, was also impregnated into the PVP/gelatin nanofibrous structure during electrospinning. The membrane thus fabricated showed antibacterial activities against both the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. AgSD release behaviour of fabricated samples indicated short-term drug delivery. It was concluded that the proposed drug-loaded membrane can be used as wound dressing, specifically, in treating skin burns.     

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full‐Thickness Skin Regeneration During Wound Healing

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full‐thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid‐graft‐dopamine and reduced graphene oxide (rGO) using a H₂O₂/HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self‐healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full‐thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full‐thickness skin repair.     

生物聚氨酯/羟基磷灰石微相分离与形状记忆性能

形状记忆功能化生物聚氨酯在医用植入体材料中备受关注,而聚氨酯的形状记忆性能与其微相分离结构密切相关。文中以可降解聚己内酯二醇(PCL-diol)、脂环形异佛尔酮二异氰酸酯(IPDI)、1,4-丁二醇(BDO)为单体通过两步法合成生物聚氨酯(PU),以溶液共混的方式加入PU基体中,制备了一系列聚氨酯/羟基磷灰石(PU/HA)复合材料。通过场发射扫描电子显微镜、傅里叶变换红外光谱、热失重分析和动态力学热分析等不同表征方法研究了HA的引入对PU基体微相分离的影响,及其与宏观形状记忆性能的关系,并考察了材料的生物安全性。结果表明,HA的引入明显促进了PU的微相分离,随着HA含量的增加,硬段与软段的玻璃化转变温度差值越大,表明微相分离程度越高。在HA质量分数低于15%时,HA的含量越高,形状回复越快,表明微相分离程度越高,形状记忆性能越好。L929细胞毒性测试结果显示,PU/HA具有良好的细胞安全性,在医用骨修复领域有潜在的应用价值。     

Hyaluronic acid (HA)-based hydrogels for full-thickness wound repairing and skin regeneration

In this work, two kinds of hyaluronic acid (HA)-based hydrogels were fabricated: one is made from physical freezing-thawing of HA solution (HA1), and the other is from chemical cross-linking of HA and polysaccharide (HA2). They were applied to repair full-thickness skin defects with New Zealand rabbits as the test animals, using powder HA and cotton dress as the references. The wound starts to heal after wounds were disinfected with iodine followed by coating with HA2, HA1, HA and cotton dress (the control), respectively. They were recorded as 4 treatments (groups), HA2, HA1, HA and the control. The healing progress was followed and tested in the duration of 56 days, and the biological repairing mechanism was explored. From the wound area alteration, white blood cell (WBC) measurements and H&E staining, HA2 was the most promising treatment in promoting the wound healing with least serious scar formation. Immunochemistry analyses and real-time PCR tests of the bio-factors involved in the wound healing, vascular endothelial growth factor (VEGF), alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1 (TGF-β1), exhibited that HA2 enhanced VEGF and α-SMA secretion but reduced TGF-β1 expression at early stage, which alleviated the wound inflammation, improved the skin regeneration and relieved the scar formation.     

Effect of hyaluronic acid incorporation method on the stability and biological properties of polyurethane–hyaluronic acid biomaterials

The high failure rate of small diameter vascular grafts continues to drive the development of new materials and modification strategies that address this clinical problem, with biomolecule incorporation typically achieved via surface-based modification of various biomaterials. In this work, we examined whether the method of biomolecule incorporation (i.e., bulk versus surface modification) into a polyurethane (PU) polymer impacted biomaterial performance in the context of vascular applications. Specifically, hyaluronic acid (HA) was incorporated into a poly(ether urethane) via bulk copolymerization or covalent surface tethering, and the resulting PU–HA materials characterized with respect to both physical and biological properties. Modification of PU with HA by either surface or bulk methods yielded materials that, when tested under static conditions, possessed no significant differences in their ability to resist protein adsorption, platelet adhesion, and bacterial adhesion, while supporting endothelial cell culture. However, only bulk-modified PU–HA materials were able to fully retain these characteristics following material exposure to flow, demonstrating a superior ability to retain the incorporated HA and minimize enzymatic degradation, protein adsorption, platelet adhesion, and bacterial adhesion. Thus, despite bulk methods rarely being implemented in the context of biomolecule attachment, these results demonstrate improved performance of PU–HA upon bulk, rather than surface, incorporation of HA. Although explored only in the context of PU–HA, the findings revealed by these experiments have broader implications for the design and evaluation of vascular graft modification strategies.     

In vitro and in vivo evaluations of phenytoin sodium-loaded electrospun PVA, PCL, and their hybrid nanofibrous mats for use as active wound dressings

In this work, polyvinyl alcohol (PVA), poly(ε-caprolactone) (PCL), and their electrospun PVA/PCL (80/20) hybrid nanofibrous mats were used for the development of active wound dressings. The biocompatibility and therapeutic effects of the developed products were studied by in vitro cell culture and in vivo experimental rat wound model. The release rate measurements by HPLC showed that the PVA nanofibrous sample containing phenytoin sodium (PHT-Na) has a higher level of the drug release compared to the hybrid PVA/PCL (80/20) and PCL nanofibrous mats. A mesenchymal stem cell was seeded on neat as well as drug-loaded PVA nanofibrous mats. The results represented that the mats provide a suitable environment for cell growth and viability. PVA nanofibers containing PHT-Na have a unique performance for fibroblasts and myofibroblasts cells formation and consequently reaching to the remodeling phase and faster healing of the wounds. Also, PHT-Na-loaded electrospun PVA nanofibrous mats showed a remarkable efficiency in wound closure compared with the treatments results from gauze, commercial wound dressing Comfeel^®Plus, and 2 % PHT-Na ointment. Histology analysis showed the formation of epidermis, the lack of necrosis, and accumulation of collagen fibers in dermis for PVA nanofibrous mats containing PHT-Na.     

Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with β-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation

Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with β-cyclodextrin in a poly(?-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0?g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24?h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing β-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.     

Evaluation of bacterial nanocellulose-based uniform wound dressing for large area skin transplantation

Bacterial nanocellulose (BNC) was biosynthesized by Gluconacetobacter xylinus. The surface area, physicochemical structure and morphology of the materials were characterized. Here provides a method for an efficient production of uniform BNC, which is beneficial for the fast characterization and evaluation of BNC. In vitro cytotoxicity of the materials was evaluated by the proliferation, the adhesion, the viability and the morphology of NIH/3T3 cells. Low cytotoxicity of the BNC was observed, and micrographs demonstrate a good proliferation and adhesion of NIH/3T3 cells on BNC. Large area full-thickness skin defects were made on the back of C57BL/6 mice in animal surgery. The wounds were transplanted with BNC films and the results compared to those in a control group. The rehabilitation of the wound surfaces and the pathological sections of mice were investigated and are discussed. Histological examinations demonstrated faster and better healing effect and lower inflammatory response in the BNC group than those in the control group. Preliminary results on wound dressings from BNC show a curative effect promoting the healing of epithelial tissue. BNC is a promising natural polymer with medical applications in wound dressings.     

Amniotic membrane extract-loaded double-layered wound dressing: evaluation of gel properties and wound healing

The conservative single-layered wound dressing system is decomposed when mixed in polyvinyl alcohol (PVA) solution, which means it cannot be used with a temperature-sensitive drug. The goal of this investigation was to make an amniotic membrane extract (AME)-loaded double-layered wound dressing with an improved healing result compared to the conservative single-layered wound dressing systems. The double-layered wound dressing was developed with PVA/sodium alginate using a freeze–melting technique; one layer was PVA layer and the other was the drug-loaded sodium alginate layer. Its gel properties were assessed compared to single-layered wound dressings. Moreover, in vivo wound-healing effects and histopathology were calculated compared to commercial products. The double-layered wound dressing gave a similar gel fraction and Young’s module as single-layered wound bandages developed with only PVA, and a similar inflammation ability and WVTR as single-layered wound dressings developed with PVA and sodium alginate. Our data indicate that these double-layered wound bandages were just as swellable, but more elastic and stronger than single-layered wound dressings comprised of the same polymers and quantities, possibly giving an acceptable level of moisture and accumulation of exudates in the wound zone. Compared to the commercial product, the double-layered wound dressing comprising 6.7% PVA, 0.5% sodium alginate and 0.01% AME significantly enhanced the wound-healing effect in the wound-healing test. Histological investigations showed that superior full-thickness wound-healing effects compared to the commercial product. Therefore, the double-layered wound dressing would be an outstanding wound-dressing system with improved wound healing and good gel property.     

Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m²/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.     

壳-芯电纺超细纤维作为药物释放载体的研究

应用同轴共纺技术制备了以L-型聚乳酸为壳层材料,盐酸四环素为主要芯质材料的壳-芯超细纤维膜,研究了这种超细纤维膜的微观结构、力学性能与药物释放特性.结果表明,药物能够包覆在一层很薄的可降解聚合物壳层中,形成一种储库型药物释放系统.纤维的直径大小对纤维膜的各项理化性能有较大影响.随壳层聚合物浓度升高,纤维的平均直径增大,力学强度降低.药物能够从纤维膜中持续释放出来.这种壳-芯超细纤维有望用于药物释放、载药缝合线和医用敷料等生物医学领域.