载药自固化磷酸钙人工骨治疗慢性骨髓炎

目的 探讨载药自固化磷酸钙人工骨（CPC）治疗慢性骨髓炎的临床疗效.方法 自2002年1月起,对8例慢性骨髓炎患者,行彻底清创后,一期植入载药自固化磷酸钙人工骨.结果 本组均获随访,随访时间为11～35个月,平均21.3个月,1例发生术后伤口表浅感染,随访期间均无骨髓炎复发,未见明显的全身反应,无再骨折,X线片显示,术后骨髓炎区被CPC充分填塞,随访时CPC部分降解成骨.结论 在病灶清除后,一期将载药自固化磷酸钙人工骨植入残留的感染性骨缺损是治疗慢性骨髓炎的较理想的方法.     

载重组人BMP-2磷酸钙联合载抗生素磷酸钙人工骨治疗慢性骨髓炎伴骨缺损的临床研究

目的 通过与单纯载抗生素磷酸钙人工骨(calcium phosphate cement,CPC)比较,探讨载重组人BMP-2(recombinant human BMP-2,rhBMP-2)CPC联合载抗生素CPC一期治疗慢性骨髓炎伴骨缺损的疗效.方法 采用单盲、前瞻性临床随机对照试验,以2018年4月-2019年4月...     

骨感染

20061294 载药自固化磷酸钙人工骨治疗慢性骨髓炎／陈红卫…∥中国骨与关节损伤杂志．-2005，20（10）．-673～675 自2002年1月起，对8例慢性骨髓炎患者，行彻底清创后，一期植入载药自固化磷酸钙人工骨（CPC）。结果：该组均获随访，随访时问为11-35个月，平均21．3个月，1例发生术后伤口表浅感染，随访期间均无骨髓炎复发，未见明显的全身反应，无再骨折，x线片显示，术后骨髓炎区被CPC充分填塞，随访时CPC部分降解成骨。结论：在病灶清除后，一期将载药自固化磷酸钙人工骨植入残留的感染性骨缺损是治疗慢性骨髓炎的较理想的方法。图2参10     

一期病灶清除载药磷酸钙人工骨充填治疗慢性骨髓炎

目的 探讨一期病灶清除载药磷酸钙人工骨(CPC)充填治疗慢性骨髓炎的临床疗效:方法 22例慢性骨髓炎患者行彻底清创后,一期植入载药CPC.结果 22例获随访(26.3±6.5)个月,患者术后均未出现过敏或毒性反应,无皮疹或高热;随访期间均无骨髓炎复发.未见明显的全身反应,无再骨折;X线片显示植入CPC与宿主骨接触紧密,界面处未见间隙存在,骨缺损处的解剖形状完全或大部分恢复,未见脱落现象,随访期内18例患者CPC部分降解成骨.结论 在病灶清除后,载药CPC一期充填残留的感染性骨缺损治疗慢性骨髓炎可有效控制感染.     

载药磷酸钙骨水泥研究进展

载药磷酸钙骨水泥(CPC)能同时满足骨缺损修复重建和局部药物治疗目的,近年来受到众多学者和临床医师关注。载荷药物和CPC之间存在比较复杂的关系,一方面载荷药物会影响CPC固化时间及其抗压强度,另一方面CPC本身理化结构和降解吸收也会影响药物释放。载药CPC药物释放受到骨水泥材料几何因素、结构参数和物理化学参数,以及药物装填量、添加剂和生物学因素等诸多因素影响。为了使载荷药物缓慢有效释放,载药微球技术被应用于载药CPC材料研究中,初步结果较为满意。目前载药CPC研究在骨科疾病中主要涉及非病理性骨缺损、感染性骨缺损、骨肿瘤和骨质疏松等。近期研究表明,载药CPC局部药物释放和治疗效果较好,并能同时满足骨修复重建的要求。但药物释放的可控性和缓释性离临床要求还有一定差距,药物对骨与软组织的细胞毒性还需进一步评估。     

载药自固化磷酸钙人工骨治疗慢性骨髓炎

慢性骨髓炎临床处理颇为困难，传统方法采用分期手术，先控制感染，消灭创面，待骨髓炎静止后再修复骨缺损，故疗程长，费用高，随着观念的不断更新，摘除死骨并植骨在临床上被逐步采用。我们自2002年1月至2004年4月，对8例慢性骨髓炎患者行彻底清创后，一期植入载药自固化磷酸钙人工骨(CPC)，取得了满意的临床疗效，现报告如下。     

载药自固化人工骨在慢性骨髓炎手术中的应用

慢性骨髓炎的临床治疗多采用病灶清除闭合冲洗吸引法、病灶清除游离组织移植复合瓣复盖骨髓炎创面、含庆大霉素的骨水泥链珠填充[1]、吻合血管的阔筋膜瓣移植[2]、利福平-珊瑚羟磷灰石载体填充[3]、载药骨水泥填充等方法,但临床存在再骨折及反复发作可能。本院于2000年5月至2002年5月,应用载药自固化磷酸钙人工骨(ACPC)治疗慢性骨髓炎伴骨缺损25例,临床上取得良好疗效。现报道如下。1资料与方法1.1临床资料:本组25例,男17例,女8例;年龄23～65岁,平均48岁。发病时间最短4个月,最长20年。其中股骨慢性骨髓炎6例,胫骨13例,髂骨1例,肱骨2例,桡…     

四肢开放性骨折伴骨缺损治疗方法的研究

目的 探讨一种简单、安全、有效的治疗开放性骨折伴骨缺损方法。方法 对98例开放性骨折伴骨缺损的病人在清创,适当固定后采用：①载药自固化磷酸钙人工骨植入;②抗生素伴自体骨植入;③早期关闭创口,后期取带血管蒂的骨块伴载药自固化磷酸钙人工骨植入。结果 对轻中度污染,骨缺损量较少的开放性骨折伴骨缺损者,采用载药自固化磷酸钙人工骨植入及抗生素伴自体骨植入治疗,二者无明显差异。对污染较重的开放性骨折伴骨缺损者,适用于载药自固化磷酸钙植入治疗。对污较重且伴有节段性缺损大于5cm的开放性骨折伴骨缺损者,适用于早期清创,后期取带血管蒂的骨块伴载药自固化磷酸钙人工骨植入治疗。结论 对开放性骨折伴骨缺损,应根据骨缺损量的多少及污染的程度选用合适的方法,以免多次手术。     

自固化磷酸钙人工骨修复骨缺损的临床应用

目的:探讨自固化磷酸钙人工骨(CPC)填充修复骨缺损的临床效果。方法:骨缺损94例,男59例,女35例;年龄11~72岁,平均39.4岁。骨缺损部位:胸腰椎38例,跟骨25例,胫骨15例,股骨7例,肱骨近端3例,桡骨远端5例,近节指骨1例。骨缺损原因:骨折塌陷复位后骨缺损63例,骨髓炎20例,骨囊肿6例,骨纤维异常增殖症4例,内生软骨瘤1例。骨缺损范围为1cm×1cm~4cm×20cm,用CPC填充修复,CPC充填量为3~42g,其中单纯CPC填充修复74例(胸腰椎骨折行椎体成形38例,骨折复位后空腔充填25例,良性骨肿瘤病灶刮除后充填11例),载药CPC填充修复骨髓炎20例。结果:所有患者均获随访,随访时间14~48个月,平均29.6个月。全部患者术后未见过敏或毒性反应,无皮疹或高热,血钙、磷、碱性磷酸酶均正常,切口无瘙痒感。随访时X线片显示,植入CPC与宿主骨接触紧密,界面处未见间隙存在,骨缺损处的解剖形状完全或大部分恢复,未见脱落现象,随访时部分患者CPC部分降解成骨。9例发生术后伤口渗出,为淡黄色清亮稀薄分泌物,细菌培养阴性,经换药后伤口愈合良好。结论:CPC填充修复骨缺损安全有效,并发症少,是理想的骨替代品,载药CPC是治疗骨髓炎的理想方法。     

含去甲万古霉素磷酸钙骨水泥填充治疗慢性骨髓炎

目的研究含去甲万古霉素磷酸钙骨水泥填充治疗慢性骨髓炎的临床疗效。方法自2008年8月至2013年12月通过对13例慢性骨髓炎患者手术彻底清创后,将含去甲万古霉素磷酸钙骨水泥填充至骨缺损内,通过随访观察创面愈合情况、骨折愈合情况及复发情况。结果 13例均获随访,随访时间12~24个月。13例患者除1例复发外,其余均临床治愈,效果令人满意。结论采用含去甲万古霉素磷酸钙骨水泥填充治疗慢性骨髓炎,因其与骨组织相容性好,反应温和,并起到填充骨缺损、诱导骨再生的作用,不用二次取出,特别是对于病灶范围不大的病例疗效满意,是一种值得进一步推广的手术治疗方案。     

全髋关节置换术后假体周围感染治疗及抗生素缓释系统研究进展

髋关节置换术后假体周围感染是临床上的灾难性疾病,往往导致假体失效,需要全身抗生素联合手术才能根治感染,给医生、患者带来巨大的负担。保留假体清创、Ⅰ期翻修具有严格的适应证,满足条件的病例少。Ⅱ期翻修仍然是假体周围感染治疗的金标准,适用所有感染状况,治疗成功率高。在Ⅱ期翻修中,抗生素缓释系统起着关键作用,抗生素缓释系统载体是目前研究的重点,包括经典的骨水泥及可吸收生物材料,骨水泥具有很强的力学强度、但是抗生素释放呈现出急剧下降的趋势;可吸收生物材料可以持续高浓度释放抗生素,但机械强度差,不能单独使用。将骨水泥与可吸收生物材料联合应用,将是一种理想的抗生素载体,骨水泥是最常用的抗生素载体,但是抗生素释放浓度24 h后急剧下降,若低于最低抑菌浓度,将难以控制感染,并增加细菌耐药的风险;可降解材料可完全释放抗生素,释放时间长、浓度高,但是机械强度低。抗生素间隔器（spacer）在控制感染中发挥着重要作用,未来的研究将如何进一步延长抗生素缓释系统抗生素释放时间、增加抗生素释放量的同时,维持材料的机械强度。     

A biodegradable antibiotic delivery system based on poly-(trimethylene carbonate) for the treatment of osteomyelitis

Background and purpose Many investigations on biodegradable materials acting as an antibiotic carrier for local drug delivery are based on poly(lactide). However, the use of poly(lactide) implants in bone has been disputed because of poor bone regeneration at the site of implantation. Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polymer that does not produce acidic degradation products. We explored the suitability of PTMC as an antibiotic releasing polymer for the local treatment of osteomyelitis.Methods This study addressed 2 separate attributes of PTMC: (1) the release kinetics of gentamicin-loaded PTMC and (2) its behavior in inhibiting biofilm formation. Both of these characteristics were compared with those of commercially available gentamicin-loaded poly(methylmethacrylate) (PMMA) beads, which are commonly used in the local treatment of osteomyelitis.Results In a lipase solution that mimics the in vivo situation, PTMC discs with gentamicin incorporated were degraded by surface erosion and released 60% of the gentamicin within 14 days. This is similar to the gentamicin release from clinically used PMMA beads. Moreover, biofilm formation by Staphylococcus aureus was inhibited by approximately 80% over at least 14 days in the presence of gentamicin-loaded PTMC discs. This is similar to the effect of gentamicin-loaded PMMA beads. In the absence of the lipase, surface erosion of PTMC discs did not occur and gentamicin release and biofilm inhibition were limited.Interpretation Since gentamicin-loaded PTMC discs show antibiotic release characteristics and biofilm inhibition characteristics similar to those of gentamicin-loaded PMMA beads, PTMC appears to be a promising biodegradable carrier in the local treatment of osteomyelitis.     

Antibiotic loaded chitosan bar. An in vitro, in vivo study of a possible treatment for osteomyelitis

A biodegradable drug delivery system of a gentamicin loaded chitosan bar with sustained antibiotic effect is described. Chitosan has proven to be a biocompatible aminopolysaccharide and a matrix for controlled release of pharmaceuticals. Combined crosslinking, solvent evaporation, and a cylinder model cutting technique was used to prepare the chitosan bar. Sustained diffusion of gentamicin into the surrounding medium was seen using a release test in vitro. Approximately 11% gentamicin was released from the bar in the first 24 hours. The gentamicin released from the bar showed significant antibacterial activity. The bar implanted in the proximal portion of the rabbit tibia produced a low blood concentration of gentamicin, but a much higher concentration was produced in local bone and in the hematoma. In all bone tissue around the bar, the gentamicin concentration exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for approximately 8 weeks. The implant caused no systemic side effects. Based on these test results together with the chitosan characteristics of biodegradable, antibiotic, and immunologic activity, the gentamicin loaded chitosan bar seems to be a clinically useful method for the treatment of bone infection. This system has an advantage over other systems in that it avoids a second operation for removal of the carrier.     

几丁糖阿霉素缓释药粒的体外实验研究

几丁糖是一种无毒、无副作用，生物相容性良好，可在体内自然降解吸收的生物材料。利用几丁糖缓慢降解的特性，将其与阿霉素制成几丁糖阿霉素缓释药粒，并进行体外释放试验及其浸出液的体外抑制ＯＳ－１１６骨肉瘤试验。结果表明，该缓释药粒可使阿霉素呈缓慢稳定的释放，其第１，２０，４０及６０天浸出液的ＯＳ－１１６骨肉瘤的抑制率分别为５８．１１％，３６．４８％，２４．３２％及２１．６２％。认为，几丁糖与阿霉素制成的缓释药粒具有良好的缓释功能，且不影响阿霉素的活性，是化疗药物缓释的极好载体，并可应用于骨肿瘤术后的局部治疗。     

Acrylic bone cement: current concept review

Acrylic bone cement has had for years an important role in orthopedic surgery. Polymethylmethacrylate (PMMA) has been extended from the ophthalmological and dental fields to orthopedics, as acrylic cement used for fixation of prosthetic implants, for remodeling osteoporotic, neoplastic and vertebral fractures repair. The PMMA bone cement is a good carrier for sustained antibiotic release in the site of infection. Joint prostheses chronic infection requires surgical removal of the implant, in order to eradicate the infection process. This can be performed in the same surgical time (one-stage procedure) or in two separate steps (two-stage procedure, which involves the use of an antibiotic-loaded cement spacer). The mechanical and functional characteristics of the spacers allow a good joint range of motion, weight-bearing in selected cases and a sustained release of antibiotic at the site of infection. The improvement of fixation devices in recent years was not accompanied by the improvement of elderly bone quality. Some studies have tested the use of PMMA bone cement or calcium phosphate as augmentation support of internal fixation of these fractures. Over the past 20 years, experimental study of acrylic biomaterials (bone cement, bioglass ceramic, cement additives, absorbable cement, antibiotic spacers) has been of particular importance, offering numerous models and projects.     

Release of gentamicin from a tricalcium phosphate bone implant.

The impregnation and elution of gentamicin antibiotic from a commercially available porous beta-tricalcium phosphate (TCP) bone implant material (Vitoss, Orthovita, Inc.) was investigated in vitro. Sustained local antibiotic release is an attractive method for the prevention of infection following surgery. The purpose of this study was to evaluate the use of the naturally forming clot that occurs within a porous tissue scaffold when combined with autologous blood or bone marrow aspirate (BMA) as a method for achieving controlled drug delivery. The diffusion of antibiotic from porous TCP scaffolds was studied using water, clotted blood, or BMA as impregnating fluids. Incorporation of the drug into the porous scaffold using clotted blood or BMA as a binder produced slowed release relative to aqueous impregnated and dried samples. Modifications were made to the elution method to simulate restricted diffusion due to surrounding clotted blood, tissue, or bone that would occur in vivo. These modified methods simulated release in a surgical site and showed long release profiles, with significant amounts of antibiotic being released for up to 2 weeks. We concluded that adding gentamicin with autologous BMA is a promising method of controlling drug release.     

Konduktives Knochenersatzmaterial mit variabler Antibiotikaversetzung

BACKGROUND: A new bone substitute, consisting of hydroxylapatite and calcium sulphate, was prepared in two formulations and analysed for its mechanical strength and antibiotic elution. MATERIAL AND METHODS: The bone substitute PerOssal has osteoconductive and degradable properties. The material has a built-in capillary structure, which results in an immediate fluid uptake. Antibiotics absorbed to the bone substitute resulted in a prolonged release rate. Mechanical strength was investigated by an unconfined compression test up to failure under both wet and dry conditions for both formulations of the bone substitute. Antibiotic release was analysed microbiologically for two antibiotics, vancomycin and gentamicin, over an elution period of 10 days using the agar diffusion method. RESULTS: The drug release analysis resulted in a prolonged release rate of both antibiotics over 10 days. In vitro the amount of gentamicin and vancomycin eluted at day 10. From one pellet still exceeded the minimal inhibitory concentration of most aetiologically important pathogens. Formulation two of the present bone substitute is significantly harder in both wet and dry conditions when compared to formulation one. Both formulations lose strength in the wet condition relative to their performance in the dry condition. However, formulation two is as hard under wet conditions as formulation one is when dry. CONCLUSION: PerOssal is a suitable new degradable osteoconductive bone substitute that can be loaded with antibiotic solutions, which are released in effective doses over 10 days. The mechanical strength of PerOssal is sufficient to support cancellous bone defects in non-weight-bearing areas or in combination with osteosynthesis.     

脂质体作为骨靶向药物载体的应用研究进展

目的：通过探究脂质体作为骨靶向药物载体的研究进展，以促进其作为特异性骨靶向给药系统进入临床应用。方法应用计算机检索PubMed、中国期刊全文数据库（ CNKI）的相关文献，选择文章内容与骨靶向脂质体相关者，同一领域文献则选择近期发表在权威杂志的文章。结果根据纳入标准选择22篇文献进行综述。结论脂质体作为药物载体，因其制备简单、无毒、无免疫原性、易携载和释放各种药物等特点而备受关注。脂质体经修饰后可通过被动靶向、主动靶向和双重靶向三种靶向方式携带药物沉积于骨中，从而使药物能选择性地作用于骨组织，这将解决一些治疗骨病的药物疗效低、不良反应大的问题。迄今为止研究最多的是主动骨靶向脂质体，即通过对脂质体表面进行化学修饰，使脂质体具有骨趋向性。目前，脂质体作为骨靶向递药系统的研究已取得较大进展，这些研究初步解决了药物骨靶向性的问题，但是脂质体要作为一个理想的骨靶向性药物载体进入临床应用尚有许多待解决的问题。     

Calcium hydroxyapatite ceramic used as a delivery system for antibiotics.

Porous blocks of calcium hydroxyapatite ceramic were evaluated as delivery systems for the sustained release of antibiotics. We tested gentamicin sulphate, cefoperazone sodium, and flomoxef sodium in powder form placed in a cylindrical cavity in calcium hydroxyapatite blocks, using in vitro studies of elution and in vivo studies in rats. Gentamicin sulphate gave a maximum concentration within the first week, which gradually decreased but was still effective at 12 weeks, when 70% of the antibiotic had been released. Even at this stage the antibiotic concentration from a 75 mg dose was five times the minimum inhibitory concentration for staphylococci. In the in vivo studies the release of gentamicin sulphate into the normal bone of rats was at similar rates and levels. The bacteriocidal activity of the drugs was not affected by packing into calcium hydroxyapatite ceramic and the blocks were completely biocompatible on histology. This new system overcomes the disadvantages of other drug delivery systems, avoiding thermal damage to the antibiotics and a second operation for the removal of the carrier. Some mechanical strength is provided by the ceramic and healing may be accelerated by bone ingrowth into its micropores.     

Copal Bone Cement Is More Effective in Preventing Biofilm Formation than Palacos R-G

Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.