Antibacterial biomaterials for skin wound dressing

Bacterial infection and the ever-increasing bacterial resistance have imposed severe threat to human health. And bacterial contamination could significantly menace the wound healing process. Considering the sophisticated wound healing process, novel strategies for skin tissue engineering are focused on the integration of bioactive ingredients,antibacterial agents included, into biomaterials with different morphologies to improve cell behaviors and promote wound healing. However, a comprehensive ...     

Evaluation of a flexible new liquid polymer wound dressing

Occlusive dressings are the foundation of wound care and have been shown to speed epithelialization and healing of surgical sites. Many different dressings have been introduced over the years including antibacterial ointments with gauze and adhesive, hydrocolloid bandages, and liquid adhesives. All of these have their limitations and advantages. We introduce our experience with a new organic polymer in solvent which when applied to a wound forms a flexible occlusive bandage. The material has been shown to have antimicrobial properties and be well-tolerated by patients.     

Wound healing dressings and drug delivery systems: a review

The variety of wound types has resulted in a wide range of wound dressings with new products frequently introduced to target different aspects of the wound healing process. The ideal dressing should achieve rapid healing at reasonable cost with minimal inconvenience to the patient. This article offers a review of the common wound management dressings and emerging technologies for achieving improved wound healing. It also reviews many of the dressings and novel polymers used for the delivery of drugs to acute, chronic and other types of wound. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. There is also a brief section on the use of biological polymers as tissue engineered scaffolds and skin grafts. Pharmacological agents such as antibiotics, vitamins, minerals, growth factors and other wound healing accelerators that take active part in the healing process are discussed. Direct delivery of these agents to the wound site is desirable, particularly when systemic delivery could cause organ damage due to toxicological concerns associated with the preferred agents. This review concerns the requirement for formulations with improved properties for effective and accurate delivery of the required therapeutic agents. General formulation approaches towards achieving optimum physical properties and controlled delivery characteristics for an active wound healing dosage form are also considered briefly.     

抗菌敷料抗菌功效体外评价研究

目的：评价抗菌敷料的体外抗菌功效。方法：本研究基于模拟临床创面微生物的实际生长状态,构建体外创面模型并建立抗菌敷料抗菌功效评价方法,用以评价抗菌敷料对金黄色葡萄球菌、铜绿假单胞菌、大肠杆菌和白色念珠菌的体外抗菌功效。结果：试验样品在12 h内抑制了金黄色葡萄球菌的增殖,在72 h内杀灭对数值未超过1.00;在24 h对铜绿假单胞菌的杀灭对数值达到4.24,随后大幅下降, 在72 h的杀灭对数值降为0.37;在12 h对大肠杆菌的杀灭对数值达到4.10,在其后至72 h内杀灭对数值均大于3.00;在12 h对白色念珠菌的杀灭对数值达到1.11,在72 h的杀灭对数值仅为0.04。结论：该抗菌敷料对金黄色葡萄球菌、铜绿假单胞菌、大肠杆菌和白色念珠菌均显示了抗菌效果,其中对铜绿假单胞菌、大肠杆菌的抗菌功效要好于金黄色葡萄球菌和白色念珠菌。     

Antimicrobial properties of silver-containing wound dressings: a microcalorimetric study

The studies reported here have been undertaken to assess the potential use of isothermal microcalorimetry in studying the antimicrobial efficacy of wound dressings that contain antimicrobial agents. The microcalorimetric technique allows non-invasive and non-destructive analysis to be performed directly on a test sample, regardless of whether it is homogeneous or heterogeneous in nature. Microcalorimetry is an established procedure that offers quantitative measurements and has the distinct advantage over traditional antimicrobial test methodologies in that calorimetric measurements are made continuously over real-time, thus the dynamic response of microorganisms to an antimicrobial agent is observed in situ. The results described in this paper are for interaction of two silver-containing wound care products AQUACEL Ag Hydrofiber (ConvaTec, Deeside, UK) and Acticoat 7 with SILCRYST (Smith and Nephew Healthcare, UK) with the wound pathogenic organisms Staphylococcus aureus and Pseudomonas aeruginosa. Both dressings are shown, microcalorimetrically, to have the capacity to kill these common wound pathogens within 1-2 h of contact. A dose-response study was conducted with the AQUACEL Ag dressing. Microcalorimetry is shown to be rapid, simple and effective in the study of the antimicrobial properties of gel forming wound dressings.     

海藻酸盐医用敷料的研究进展

海藻酸盐(alginate)是一类从褐藻中提取的天然线性多糖,具有无毒、可生物降解、生物相容性高的特点,海藻酸盐的高吸湿性和凝胶性,使其在现代伤口敷料方面得到了广泛应用。海藻酸盐敷料则具有成本低、使用方便、能促进伤口愈合的特点,有海绵形式、纤维形式和水凝胶等形式,作为医用敷料有广阔应用前景。本文对海藻酸医用辅料的主要特点和不同形式的应用进行了综述,并展望了其应用前景。     

Application of chitosan-based nanoparticles in skin wound healing

The rising prevalence of impaired wound healing and the consequential healthcare burdens have gained increased attention over recent years. This has prompted research into the development of novel wound dressings with augmented wound healing functions. Nanoparticle(NP)-based delivery systems have become attractive candidates in constructing such wound dressings due to their various favourable attributes. The non-toxicity, biocompatibility and bioactivity of chitosan(CS)-based NPs make them ideal...     

Surgical antibiotic irrigations.

Instillation of antibiotic solutions into surgical wound sites seems empirically attractive since relatively high concentrations of antibacterial agents can be applied directly to the probable site of infection. However, systemic effects provided by antibiotic assimilated from sites of application are responsible for much of the activity and toxicity of antibiotic irrigations. The most appropriate drugs and dosages for use as prophylactic antibiotic irrigations have not been determined. Most controlled trials conducted in recent years have utilized various cephalosporins in concentrations of 1 to 4 g/L. In some of these trials, surgical irrigation has been found as effective as prophylactic intravenous antibiotics, which are the proven and accepted standard. Reported cases of toxicity associated with antibiotic irrigations are few in number, excepting neomycin, which has caused postoperative respiratory depression/apnea, permanent deafness, and renal failure.     

血余炭纳米纤维膜抗菌活性的实验研究

目的:制备新型载药止血材料血余炭纳米纤维膜,并探讨其体内、体外的抗菌性能。方法:采用静电纺丝技术,将血余炭作为添加药物,以生物相容性较好的聚乳酸作为纳米纤维膜基体,制备了一种新型的载药止血材料。采用抑菌环实验法测定医用脱脂纱布、抗菌医用敷料、未载血余炭纳米纤维膜和载血余炭纳米纤维膜对金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌的抑菌环直径;选用兔感染创面模型,使用材料对创面进行治疗,通过肉眼和组织病理学观察、组织内细菌计数等方法对各组材料的抗菌性能进行研究。结果:血余炭纳米纤维膜纤维直径相对较小,平均直径为400 nm,载入的血余炭与成纤维聚合物之间具有良好的相容性。血余炭纳米纤维膜在体外对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌均有一定的抑制效果;肉眼和组织学观察,血余炭纳米纤维膜治疗后的动物模型伤口炎症反应明显小于其他组;血余炭纳米纤维膜治疗后感染伤口细菌数量为(7.62±1.87)×104个.g-1组织,与空白对照组比较显著减少,差异具有统计学意义(P<0.01)。结论:血余炭纳米纤维膜具有良好的体内、体外抗菌性能。     

Novel chitosan and bacterial cellulose biocomposites tailored with polymeric nanoparticles for modern wound dressing development

Dressing biomaterials play a key role in wound management keeping a moisture medium and protecting against external factors. Natural and synthetic materials could be used as dressings where chitosan and bacterial cellulose is one of the most important solutions. These biopolymers have been used for wound dressing based on their non-toxic, biodegradable, and biocompatible features. In this study, biocomposites based on bacterial cellulose and chitosan membranes tailored with antimicrobial loaded poly(N-isopropylacrylamide)/polyvinyl alcohol nanoparticles were prepared. Core-shell polymeric nanoparticles, bacterial cellulose/chitosan membranes, and biocomposites were independently loaded with silver sulfadiazine, a well-known sulfonamide antibacterial agent used in the therapy of mild-to-moderate infections for sensitive organisms. The chemistry, structure, morphology, and size distribution were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), RAMAN spectroscopy, Scanning electron (SEM) and Transmission electron microscopy (TEM), and Dynamic light scattering (DLS). In vitro release behaviors of silver sulfadiazine from polymeric nanoparticles and biocomposites were investigated. The biological investigations revealed good biocompatibility of both the nanoparticles and the biocomposites in terms of human dermal fibroblasts viability and proliferation potential. Finally, the drug-loaded polymeric biomaterials showed promising characteristics, proving their high potential as an alternative support to develop a biocompatible and antibacterial wound dressing.     

A review of the in vivo and in vitro toxicity of silver and gold particulates: Particle attributes and biological mechanisms responsible for the observed toxicity

This review is concerned with evaluating the toxicity associated with human exposure to silver and gold nanoparticles (NPs), due to the relative abundance of toxicity data available for these particles, when compared to other metal particulates. This has allowed knowledge on the current understanding of the field to be gained, and has demonstrated where gaps in knowledge are. It is anticipated that evaluating the hazards associated with silver and gold particles will ultimately enable risk assessments to be completed, by combining this information with knowledge on the level of human exposure. The quantity of available hazard information for metals is greatest for silver particulates, due to its widespread inclusion within a number of diverse products (including clothes and wound dressings), which primarily arises from its antibacterial behaviour. Gold has been used on numerous occasions to assess the biodistribution and cellular uptake of NPs following exposure. Inflammatory, oxidative, genotoxic, and cytotoxic consequences are associated with silver particulate exposure, and are inherently linked. The primary site of gold and silver particulate accumulation has been consistently demonstrated to be the liver, and it is therefore relevant that a number of in vitro investigations have focused on this potential target organ. However, in general there is a lack of in vivo and in vitro toxicity information that allows correlations between the findings to be made. Instead a focus on the tissue distribution of particles following exposure is evident within the available literature, which can be useful in directing appropriate in vitro experimentation by revealing potential target sites of toxicity. The experimental design has the potential to impact on the toxicological observations, and in particular the use of excessively high particle concentrations has been observed. As witnessed for other particle types, gold and silver particle sizes are influential in dictating the observed toxicity, with smaller particles exhibiting a greater response than their larger counterparts, and this is likely to be driven by differences in particle surface area, when administered at an equal-mass dose. A major obstacle, at present, is deciphering whether the responses related to silver nanoparticulate exposure derive from their small size, or particle dissolution contributes to the observed toxicity. Alternatively, a combination of both may be responsible, as the release of ions would be expected to be greater for smaller particles.     

Soft antibacterial agents

Hard drugs have been defined as drugs that are biologically active and non-metabolizable in vivo. Soft drugs are defined as drugs, which are characterized by predictable and controllable in vivo destruction (i.e. metabolism) to form non-toxic products after they have achieved their therapeutic role. Quaternary ammonium compounds, such as benzalkonium chloride, are hard antibacterial agents. Their toxicity limits their usage in humans and animals, and their chemical stability limits their usage for general environmental sanitation. Furthermore, due to their stability they are prone to induce selective antimicrobial pressure and bacterial resistance. Soft analogs of the currently available hard antibacterial agents are less toxic. However, although the soft analogs have been shown to possess antibacterial activity in in vitro studies, it is likely that their in vivo activity will be hampered by their chemical instability.     

Wound Dressings Based on Chitosans and Hyaluronic Acid for the Release of Chlorhexidine Diacetate in Skin Ulcer Therapy

In the present work wound dressings, based on chitosan hydrochloride (HCS), 5-methyl-pyrrolidinone chitosan (MPC), and their mixtures with an anionic polymer, hyaluronic acid (HA), were prepared by freeze-drying. Chlorhexidine diacetate (CX) was used as an antimicrobic drug. The mechanical properties of the wound dressings were investigated. In particular, the wound dressings were subjected to dynamic hydration measurements to evaluate their capability to absorb wound exudate and to rheological analysis to investigate their resistance to mechanical stresses on hydration. The wound dressings were also characterized for drug release properties. The antioxidant and antimicrobial activities of medicated and non-medicated wound dressings were also investigated. All the wound dressings are characterized by mechanical resistance suitable for skin application. The addition of hyaluronic acid to chitosans leads to a reduction in wound dressing hydration properties and a modulation of drug release. The wound dressing based on MPC is characterized by the highest elastic properties and by the best scavenger activity. Antimicrobial activity against bacteria and C. albicans is shown by the dressing based on chitosan also in absence of chlorhexidine.     

Wound dressings based on chitosans and hyaluronic acid for the release of chlorhexidine diacetate in skin ulcer therapy

In the present work wound dressings, based on chitosan hydrochloride (HCS), 5-methyl-pyrrolidinone chitosan (MPC), and their mixtures with an anionic polymer, hyaluronic acid (HA), were prepared by freeze-drying. Chlorhexidine diacetate (CX) was used as an antimicrobic drug. The mechanical properties of the wound dressings were investigated. In particular, the wound dressings were subjected to dynamic hydration measurements to evaluate their capability to absorb wound exudate and to rheological analysis to investigate their resistance to mechanical stresses on hydration. The wound dressings were also characterized for drug release properties. The antioxidant and antimicrobial activities of medicated and non-medicated wound dressings were also investigated. All the wound dressings are characterized by mechanical resistance suitable for skin application. The addition of hyaluronic acid to chitosans leads to a reduction in wound dressing hydration properties and a modulation of drug release. The wound dressing based on MPC is characterized by the highest elastic properties and by the best scavenger activity. Antimicrobial activity against bacteria and C. albicans is shown by the dressing based on chitosan also in absence of chlorhexidine.     

Local anesthetic lidocaine-encapsulated polymyxin–chitosan nanoparticles delivery for wound healing: in vitro and in vivo tissue regeneration

In relieving local pains, lidocaine, one of ester-type local anesthetics, has been used. To develop the lidocaine membranes of enhanced local anesthetic effects, we have designed to establish the composition of wound dressings based on lidocaine chloride (LCH) (anesthetic drug)-loaded chitosan (CS)/polymyxin B sulfate (PMB). The LCH membranes (LCH-CS/PMB) was fabricated by the LCH oxide solutions within the CS/PMB matrix. The influences of different experimental limitations on CS/PMB membrane formations were examined. The double membrane particle sizes were evaluated by scanning electron microscopy (HR-SEM). Additionally, antibacterial efficacy was developed for gram-positive and negative microorganisms. Moreover, we examined in vivo healing of skin wounds formed in mouse models over 16 days. In contrast to the untreated wounds, rapid healing was perceived in the LCH-CS/PMB-treated wound with less damaging. These findings indicate that LCH-CS/PMB-based bandaging materials could be a potential innovative biomaterial for tissue repair and regeneration for wound healing applications in an animal model.     

壳聚糖-左氧氟沙星长效缓释敷料的体外细胞毒性和抗菌效果研究

【摘要】目的 研究壳聚糖-左氧氟沙星长效缓释敷料的体外细胞毒性、抗菌效果以及肿瘤坏死因子（TNF）-α作为评价抗菌效果指标的可行性。方法 参照ISO 10993-5:2009评价该敷料的细胞毒性;制作染菌创伤白兔模型15只并分为3组,空白对照组用凡士林油纱包扎,阳性对照组用纳米银创伤贴包扎,实验样品组用壳聚糖-左氧氟沙星长效缓释敷料包扎,于6 h、1 d、4 d、7 d,采用活组织培养法检测3组的菌落数,用双抗体夹心法检测TNF-α含量,与菌落数实验结果进行比较。结果 该敷料体外细胞毒性反应为0级;实验样品组4个时点的菌落数均低于空白对照组,在6 h、1 d、4 d时,实验样品组均低于阳性对照组（P < 0.05）;实验样品组的TNF-α含量在6 h、1 d、4 d、7 d时低于空白对照组,在6 h、1 d时显著低于阳性对照组（P < 0.05）。结论 壳聚糖-左氧氟沙星长效缓释敷料无细胞毒性,具有长效抗菌能力,TNF-α不能作为评价抗菌效果的指标。     

Ambulatory use of parenteral antibacterials: contemporary perspectives

Outpatient parenteral antimicrobial therapy (OPAT) offers increased patient comfort and convenience in appropriately selected patients who require parenteral antibacterial therapy, as well as opportunity for cost savings. Home-based programmes, with drugs being administered by the patient or the caregiver, have become the norm in the USA. Choice of drugs for OPAT is based on antimicrobial spectrum, dosage regimen, drug stability, toxicity profile, and cost. Over the past decade, availability of sophisticated programmable pumps has allowed a wider range of antimicrobial agents to be used in the ambulatory setting. The most popular antibacterial agents in OPAT programmes in the USA are vancomycin and beta-lactams.     

An in vitro method for the quantitative determination of the antimicrobial efficacy of silver-containing wound dressings

Treatment with silver-containing wound dressings is becoming an increasingly popular strategy to eliminate growth of opportunistic wound pathogens during the healing process. However, there are concerns over the possible side-effects of silver to the patient; coupled to the cost of silver as an ingredient there is a desire to ensure that wound dressings contain the least quantity of active ingredient to ensure the minimum bactericidal concentration (MBC) of silver is maintained in the wound environment. This requires the ability to determine the efficacy of silver directly within the wound environment; an extremely complicated task that is difficult using classical (plate counting) microbiological assays because these cannot be conducted in situ. Here, we report a quantitative method for determining the efficacy of silver in wound dressings using an isothermal calorimetric method. The growth curves of P. aeruginosa (NCIMB 8628) were recorded in growth medium and in growth medium containing AQUACEL Ag Hydrofiber dressing. It was found that 10 mg of dressing was sufficient to ensure no detectable growth of organism in 2.5 mL of medium inoculated to 10(6) cfu/mL. This corresponded to a silver load of 1.1x10(-6) moles (equivalent to 4.4x10(-4) M, in the volume of medium used in the experiment). Experiments conducted with silver nitrate rather than dressing indicated the MBC of silver against P. aeruginosa was 1x10(-4) M. The results suggested that not all of the silver in the dressing was bioavailable, at least over the lifetime of the experiment. One advantage of this effect would be the lack of excess availability of the silver, which allays fears of potential toxicity to the patient and may provide an extended period of time over which the dressing is bactericidal.     

An innovative bi-layered wound dressing made of silk and gelatin for accelerated wound healing

In this study, the novel silk fibroin-based bi-layered wound dressing was developed. Wax-coated silk fibroin woven fabric was introduced as a non-adhesive layer while the sponge made of sericin and glutaraldehyde-crosslinked silk fibroin/gelatin was fabricated as a bioactive layer. Wax-coated silk fibroin fabrics showed improved mechanical properties compared with the non-coated fabrics, but less adhesive than the commercial wound dressing mesh. This confirmed by results of peel test on both the partial- and full-thickness wounds. The sericin-silk fibroin/gelatin spongy bioactive layers showed homogeneous porous structure and controllable biodegradation depending on the degree of crosslinking. The bi-layered wound dressings supported the attachment and proliferation of L929 mouse fibroblasts, particularly for the silk fibroin/gelatin ratio of 20/80 and 0.02% GA crosslinked. Furthermore, we proved that the bi-layered wound dressings promoted wound healing in full-thickness wounds, comparing with the clinically used wound dressing. The wounds treated with the bi-layered wound dressings showed the greater extent of wound size reduction, epithelialization, and collagen formation. The superior properties of the silk fibroin-based bi-layered wound dressings compared with those of the clinically used wound dressings were less adhesive and had improved biological functions to promote cell activities and wound healing. This novel bi-layered wound dressing should be a good candidate for the healing of full-thickness wounds.     

Emerging strategies in infectious diseases: new carbapenem and trinem antibacterial agents

Beta-lactam antibiotics represent the most commonly prescribed antibacterial agents. New beta-lactams have been introduced continuously as many bacteria have developed resistance to older agents. In the late 1970s, a new class of exceptionally broad spectrum beta-lactams, the carbapenems, was identified. Despite being a very potent compound, the antibacterial activity of the first carbapenem, imipenem, was compromised because of hydrolysis by the renal dehydropeptidase enzyme (DHP-1), and it is now coadministered with a potent competitive inhibitor of the DHP-1 enzyme, cilastin. Molecular modifications in the carbapenem nucleus were able to increase stability to DHP-1 and retain the antibacterial activity. However, some important pathogenic bacteria were found to be resistant to this new class of agents. In addition, other clinically important gram-negative species, such as Pseudomonas aeruginosa, developed resistance mainly by the production of potent beta-lactamases and reduced permeability of the outer membrane. Since the discovery of imipenem/cilastatin, a great number of carbapenems have been developed, and a few of them have been marketed. Stability to hydrolysis by DHP-1 and decrease in toxicity were achieved by meropenem and biapenem. However, only a slight increase in the antibacterial potency and spectrum has been accomplished with either the new marketed or experimental parenteral compounds. In addition, compounds that can be administered orally, such as the carbapenens faropenem, CS-834 and MK-826, and the trinem sanfetrinem, have been developed. However, when compared with the parenterally administered compounds, the oral agents seem to lose some in vitro antibacterial activity, especially against P. aeruginosa.