骨科金属植入物表面载药抗菌涂层的研究进展

目的总结近年来骨科金属植入物表面载药抗菌涂层的研究进展。方法检索查阅近年来国内外关于骨科金属植入物表面载药抗菌涂层的相关研究报道,对研究现状、分类及发展趋势进行总结。结果骨科金属植入物表面载药抗菌涂层在药物释放方式上可分为被动释放型和主动释放型。被动释放型载药涂层在植入体内后,无论植入物周围有无细菌都会持续被动地释放药物;而主动释放型载药涂层在植入物周围无感染时不释放或少量释放所搭载的药物,仅当其周围出现感染时,主动释放搭载药物,实现智能抗菌。结论药物的持续稳定释放是各种抗菌涂层需解决的关键问题,能够对细菌响应性释放载药的智能型抗菌涂层是今后载药抗菌涂层的发展方向。     

抗感染骨科内置入材料的研究进展

战创伤的骨折发生率极高,且多为开放性骨折,战场环境及内外固定器械的使用等诸多因素使伤员感染率、致死率高。手术方式的改进,抗感染内固定器械开发使用,及敏感抗生素应用等措施是治疗感染的有效方式。抗菌内置物材料从根源上抑制细菌生物膜形成,提高局部抗菌能力,理论上可改善救治效果。目前骨科内置入抗菌材料是以钛合金为基体,通过物理或化学方法,在表面形成各种不同性质的涂层来提高抗菌性能。根据涂层的种类可将其分为抗生素涂层和非抗生素涂层,后者包括有机涂层、无机涂层、抗菌黏附性涂层和生物活性聚合物涂层。尽管涂层众多,但因其抗菌效果不明确、骨愈合不理想、耐药性和制作成本高等原因,目前仍不能广泛应用于临床。     

人工关节置换术后假体周围感染的生物膜研究进展

目的综述人工关节置换术后假体周围感染生物膜研究的最新进展。方法查阅近年有关人工关节术后感染及生物膜研究方面的最新文献,对于生物膜的形成、生物膜的耐药性、人工关节假体感染的诊断、治疗、预防的最新进展进行回顾,综合分析。结果生物膜是细菌在生物医学材料表面形成的特殊膜样结构,是假体周围感染诊断和治疗的焦点。生物膜可通过其中细菌的变异提高耐药性并不易检测诊断。目前已有声波降解基因检测等手段进行诊断。而假体涂层的载药设计是预防生物膜形成的有效方法。结论针对生物膜的生物学特性进行积极的预防,早期的诊断和恰当的治疗,是假体周围感染诊治的关键所在。应用新技术检测辅助诊断和将“自清洁表面”预防生物膜形成,可能是诊治假体周围感染的突破点。     

纳米银在骨科中的应用进展

内置入物感染是骨科手术失败发生的主要原因。为了降低感染的风险,防止置入物表面生物膜形成的研究比较广泛。目前的研究结果显示了纳米银具有良好的抗菌性能。其在创伤置入物、肿瘤假体、骨水泥、银-羟基磷灰石涂层等中的应用展示了良好的抗菌效果。虽然纳米银在体外和体内实验中展现了良好的抗菌结果,但是其临床研究的样本仍比较少。未来的研究方向应进一步探讨纳米银的相关副作用,以确保其使用的有效性和安全性。。     

骨科植入物表面抗感染涂层的研究进展

植入物感染是骨科内固定术后的严重并发症,预防此类感染的研究已成为当今医学的一个热点.随着对植人物感染特殊发病机制的认识的不断深入,许多学者愈来愈重视改善植入物与组织接触的界面,即试图通过改变植入物表面的特性阻止致病菌的黏附、繁殖及生物膜形成,最终彻底预防感染发生.     

壳聚糖表面改性钛合金材料的研究进展

钛合金材料生物性能良好,是骨科常用的内植入材料,但其骨整合性及抗菌性能较差,需进行表面改性以弥补其不足之处。壳聚糖具有良好的生物相容性及成膜性,且可作为载体将目标药物引入钛合金表面,可有效改善钛合金材料的生物学性能,增加其使用范围。本文对近几年壳聚糖表面改性钛合金材料的相关研究进行归纳总结,从壳聚糖涂层改性的方式、钛合金材料成骨性及抗菌性的改善3个方面展开论述,以期为钛合金材料涂层改性在临床中的应用提供指导依据。     

带抗菌效能骨科内植物的研制与体外实验研究

目的 ①研制一种可用于预防和治疗骨折内固定术后感染的骨科内植物.②对本带抗菌效能骨科内植物进行体外药物释放规律及持续时间测定,以了解其体外缓释规律及经过环氧乙烷灭菌对其抗菌效能的影响.方法 在长约5 cm,直径4 mm的圆柱形不锈钢短棒上均匀涂布0.4 g头孢唑啉钠,其外涂布丙烯酸树脂等多种高分子可降解有机物的混合物,即制成试验用带抗菌效能内植物.将带有涂层的8根不锈钢短棒随机分为2组,其中一组经环氧乙烷灭菌,将其分别置入10 ml pH=7.40的PBS磷酸盐缓冲液中,并保持其处于37℃的环境中,用高效液相色谱法测量溶液中头孢唑啉钠的浓度变化及其有效抑菌时问.结果 第1～2天本带抗菌效能骨科内植物所释放出的头孢唑啉钠保持一个较高的浓度,自第3天开始平缓的下降,第17天时8根试管最低浓度仍高达7.1 μg/ml(头孢唑啉钠对金黄色葡萄球菌的最低抑菌浓度为0.1～6.3 μg/ml),且环氧乙烷灭菌过程对其抗菌效能无任何影响.结论 用本涂层方法制备的自带抗菌效能骨科内植物具有较强且持久的抗菌能力,可接受环氧乙烷灭菌,对防治开放性骨折术后感染具有良好的临床应用前景.     

噬菌体治疗在骨科植入物感染中的研究进展

随着植入材料在骨科疾病治疗中的应用逐渐普及, 植入物相关并发症日益增多, 其中以感染为最为严重。采取手术取出感染植入物并延长抗菌药物用药时间已被视为根除感染的有效策略。然而, 由于抗菌药物耐药和生物膜的存在, 感染难以控制或复发的情况屡见不鲜, 对患者健康构成严重威胁。最新研究结果显示, 噬菌体不仅可以直接杀灭致病菌, 还具备降解生物膜的能力。联合使用噬菌体和抗菌药物, 在临床试验中展现出了良好的治疗效果, 有望成为处理植入物相关感染的有效解决方案。     

骨科镁基植入物表面涂层改性技术的研究进展

镁及镁合金具有优异的机械性能、可降解性和生物相容性, 这使其在骨科领域得到广泛关注与研究。但镁及镁合金过快的降解速度无法匹配骨骼自身愈合速度, 并可能对周围细胞定植生长与分化产生不利影响, 引起植入物早期松动, 从而限制其在临床上的广泛应用。在解决镁植入物腐蚀速率不可控问题方面, 表面涂层改性是一种可行且极具应用前景的抗腐蚀方案。表面涂层改性技术可以通过改善植入物表面骨诱导能力(如以磷酸盐陶瓷为基础的仿生涂层)或改善抗腐蚀性能(如耐磨损耐腐蚀的微弧氧化涂层、具有自修复潜力的植酸涂层)来优化骨-植入物界面的整合。在调控镁植入物降解速率的同时, 还可通过复合成分改性实现促骨整合、药物传递、光热治疗等多功能应用。通过列举骨科镁植入物表面不同的涂层改性方案的优缺点、总结各种制备工艺中的关键技术以及对其复合改性方案进行探讨, 可为制备满足骨科临床应用需求的多功能镁植入物提供参考。     

生物膜的形态学研究进展

随着社会发展,高能量开放性创伤的发生率显著上升.我国是这类创伤的致伤致残率较高的国家之一[1].这类创伤的特点是:伤口容易感染,感染后难以治愈,形成慢性骨髓炎.究其原因是:细菌易黏附于骨科内固定物之类的惰性物体表面,如不能及时有效的清除这些细菌,则可能形成耐药的生物膜,成为院内感染的潜在危险因素[2].     

Antimicrobial peptides (AMP) in biofilm induced orthopaedic device-related infections

Orthopaedic device-related infection (ODRI) represent is one of the most challenging complications to manage in orthopaedic and trauma surgery. Biofilm formation is one of the crucial steps in the development of implant related orthopaedic infections due to the surface-adherent bacteria. Bacterial biofilms have several innate antimicrobial resistance mechanisms and hence difficult to eliminate with conventional antibiotics. Chronic, indolent, unresponsive infection can lead to clinical disability affecting quality of life with socio-economic consequences and compromised patient related health care outcomes. Although there is a basic understanding of the mechanism of biofilm associated antimicrobial resistance, enhanced knowledge, innovative treatment strategies and new therapeutic modalities is the need of the hour to manage biofilm associated Orthopaedic device-related infection (ODRI). Antimicrobial peptides (AMPs) represent an exciting opportunity to treat biofilm infections due to their diverse mechanisms of action. This article highlights the current role and mechanism of Antimicrobial peptides (AMPs) in preventing and eradicating Orthopaedic device-related infection (ODRI).     

Multi‐disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee

Like any foreign object, orthopaedic implants are susceptible to infection when introduced into the human body. Without additional preventative measures, the absolute number of annual prosthetic joint infections will continue to rise, and may exceed the capacity of health care systems in the near future. Bacteria are difficult to eradicate from synovial joints due to their exceptionally diverse taxonomy, complex mechanistic attachment capabilities, and tendency to evolve antibiotic resistance. When a primary orthopaedic implant fails from prosthetic joint infection, surgeons are generally challenged by limited options for intervention. In this review, we highlight the etiology and taxonomic groupings of bacteria known to cause prosthetic joint infections, and examine their key mechanisms of attachment. We propose that antimicrobial strategies should focus on the most harmful bacteria taxa within the context of occurrence, taxonomic diversity, adhesion mechanisms, and implant design. Patient‐specific identification of organisms that cause prosthetic joint infections will permit assessment of their biological vulnerabilities. The latter can be targeted using a range of antimicrobial techniques that exploit different colonization mechanisms including implant surface attachment, biofilm formation, and/or hematogenous recruitment. We anticipate that customized strategies for each patient, joint, and prosthetic component will be most effective at reducing prosthetic joint infections, including those caused by antibiotic‐resistant and polymicrobial bacteria. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:177–186, 2016.     

The role of biofilm infection in urology

In the process of endourological development a great variety of foreign bodies have been invented besides urinary catheters on which biofilm can be formed. Bacteria in the biofilm are less sensible to antibiotics. An additional problem of medical biomaterials in the urinary tract environment is the development of encrustation and consecutive obstruction. In this review, we tried to sum up the conditions where biofilm formation has a great impact on the development or maintenance of urological infections and on treatment success. Modification of the biomaterial surface seems to be the most promising prevention strategy for bacterial biofilms. Easier methods for diagnosing and quantifying biofilm infection, to develop more specific antimicrobial agents and ideal device surfaces would surely help the fight against biofilm formation.     

Update on biofilm infections in the urinary tract

Purpose

Biofilm infections have a major role in implants or devices placed in the human body. As part of the endourological development, a great variety of foreign bodies have been designed, and with the increasing number of biomaterial devices used in urology, biofilm formation and device infection is an issue of growing importance.

Methods

A literature search was performed in the Medline database regarding biofilm formation and the role of biofilms in urogenital infections using the following items in different combinations: ??biofilm,?? ??urinary tract infection,?? ??bacteriuria,?? ??catheter,?? ??stent,?? and ??encrustation.?? The studies were graded using the Oxford Centre for Evidence-based Medicine classification.

Results

The authors present an update on the mechanism of biofilm formation in the urinary tract with special emphasis on the role of biofilms in lower and upper urinary tract infections, as well as on biofilm formation on foreign bodies, such as catheters, ureteral stents, stones, implants, and artificial urinary sphincters. The authors also summarize the different methods developed to prevent biofilm formation on urinary foreign bodies.

Conclusions

Several different approaches are being investigated for preventing biofilm formation, and some promising results have been obtained. However, an ideal method has not been developed. Future researches have to aim at identifying effective mechanisms for controlling biofilm formation and to develop antimicrobial agents effective against bacteria in biofilms.     

Device-related infections: a review

The use of surgically implanted devices has increased as a result of their beneficial effect on quality of life, and in some circumstances, on patient survival rates. They can, however, be associated with a variety of complications, the most dreaded being infection. Device-related infections are important to understand because of the morbidity and mortality associated with them. Frequently, patients are managed with hospitalization, prolonged courses of antibiotics, and surgical interventions, all of which can negatively impact on patients' quality of life. Such care is also associated with increased costs to health care systems. Furthermore, these infections often represent a diagnostic challenge because of the lack of consensus definition of what constitutes an infection and its severity, as well as the paucity of well-designed, large studies addressing optimal methods of investigation and management. An implant-associated infection is defined as a host immune response to one or more microbial pathogens on an indwelling implant. An understanding of the pathogenesis of these infections provides a rationale for management. Development of device-related infections begins with colonization of the foreign material, followed by a complex metamorphosis by the microorganisms with resultant biofilm formation. In this surface-associated form, bacteria have altered phenotypic properties. This change, in conjunction with the physical protective layer provided by the biofilm, renders antimicrobial therapy ineffective when used alone. Because the microorganisms are able to reside on the hardware, they proliferate and cause local damage, such as loosening of implanted devices, wound dehiscence, or disruption of prosthetic valves, as well as systemic manifestations, such as fever or embolic phenomenon. The onset and clinical manifestations of device-related infections vary with the pathogen involved, as well as which component of the device is affected. The time period after device implantation that signs and symptoms develop can assist in the selection of empiric antimicrobial therapy. Optimal diagnostic microbiologic specimens are paramount in tailoring the antimicrobial therapy, which almost always has to be given for a prolonged period of time. Surgical removal of the device is usually necessary. Some studies of limited types of device-related infections, however, have defined indications for which salvage therapy may be warranted. In addition, some patients are not candidates for, or may not want, further surgical interventions, in which case indefinite suppressive antimicrobial therapy may be considered. This review provides an overview of infections related to various neurosurgical, cardiac, and orthopedic devices, as well as those related to cochlear, breast, and penile prostheses, with discussion of definitions of such infections, along with microbiology, pathogenesis, and management guidelines, including the limited indications for salvage techniques.     

Antimicrobial coated implants in trauma and orthopaedics–A clinical review and risk-benefit analysis

Implant-associated infections remain a major issue in orthopaedics and antimicrobial functionalization of the implant surface by antibiotics or other anti-infective agents have gained interest. The goal of this article is to identify antimicrobial coatings, for which clinical data are available and to review their clinical need, safety profile, and their efficacy to reduce infection rates.PubMed database of the National Library of Medicine was searched for clinical studies on antimicrobial coated implants for internal fracture fixation devices and endoprostheses for bone surgery, for which study design, level of evidence, biocompatibility, development of resistance, and effectiveness to reduce infection rates were analyzed.Four different coating technologies were identified: gentamicin poly(d, l-lactide) coating for tibia nails, one high (MUTARS^®) and one low amount silver (Agluna) technology for tumor endoprostheses, and one povidone-iodine coating for titanium implants. There was a total of 9 published studies with 435 patients, of which 7 studies were case series (level IV evidence) and 2 studies were case control studies (level III evidence).All technologies were reported with good systemic and local biocompatibility, except the development of local argyria with blue to bluish grey skin discoloration after the use of silver MUTARS^® megaendoprostheses. For the local use of gentamicin, there is contradictory data on the risk of emergence of gentamicin-resistance strains, a risk that does not seem to exist for silver and iodine based technologies. Regarding reduction of infection rates, one case control study showed a significant reduction of infection rates by Agluna silver coated tumor endoprostheses.Based on socio-economic data, there is a strong need for improvement of infection prevention and treatment strategies, including implant coatings, in fracture care, primary and revision arthroplasty, and bone tumor surgery. The reviewed gentamicin, silver Agluna, and povidone-iodine technologies have shown a good risk benefit ratio for patients. Further data from randomized control trials are desirable, although this will remain challenging in the context of infection prevention due to the required large sample size of such studies.     

Antimicrobial technology in orthopedic and spinal implants

Infections can hinder orthopedic implant function and retention.Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion.Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems,material science,immunology,and polymer chemistry are in development and early clinical use.This review outlines orthopedic implant antimicrobial technology,its current applications and supporting evidence,and clinically promising future directions.     

Assessment of the antimicrobial activity of acellular vascular grafts

Several studies have reported biological vascular grafts to be more resistant to microbial infection than synthetic counterparts in?vivo. Indeed, small intestinal submucosa (SIS) materials have previously been reported to be antimicrobial. The aim of this study was to assess the antimicrobial activity and the ability to resist biofilm formation of a novel acellular vascular graft and compare it to commercially available alternatives using a range of organisms: MRSA, MSSA, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa and Candida albicans. This was achieved using a modified disk diffusion assay and extraction of the materials into solution followed by minimum inhibitory concentration assays. To assess resistance to biofilm formation a novel biofilm assay was developed which compared the total colony forming units (CFU) recovered from each material and identification of the percentage of CFU which were loosely attached, residing within the biofilm or attached to the biomaterial. The results indicated a lack of antimicrobial activity for all materials tested, including SIS. The biological materials were more resistant to the formation of a biofilm compared to Dacron.     

The role of biofilm on orthopaedic implants: the “Holy Grail” of post-traumatic infection management?

The development of post-traumatic infection is potentially a limb threatening condition. The orthopaedic trauma literature lags behind the research performed by our arthroplasty colleagues on the topic of implant-related infections. Surgical site infections in the setting of a recent ORIF are notoriously hard to eradicate due to biofilm formation around the implant. This bacteria-friendly, dynamic, living pluri-organism structure has the ability to morph and adapt to virtually any environment with the aim to maintain the causative organism alive. The challenges are twofold: establishing an accurate diagnosis with speciation/sensitivity and eradicating the infection. Multiple strategies have been researched to improve diagnostic accuracy, to prevent biofilm formation on orthopaedic implants, to mobilize/detach or weaken the biofilm or to target specifically bacteria embedded in the biofilm. The purpose of our paper is to review the patho-physiology of this mysterious pluri-cellular structure and to summarize some of the most pertinent research performed to improve diagnostic and treatment strategies in biofilm-related infections.