摘要
研究背景
AO组织2006年报道开放性骨折的感染率是3~40%(闭合性骨折的感染率为1.5%),在受伤当时,高于60%的开放性骨折就受到了细菌的污染。而在战时火器伤中,严重的软组织损坏和污染导致在伤道周围0.5cm范围内出现了大量的细菌,即使经过了充分的伤口清创,骨和软组织的感染率仍有25% ~ 40%。Maurer等认为在开放性胫骨骨折中使用内固定后,感染率又再增高了30%。例如,在美国,每年大约200万医院感染病例中,有几乎一半与内植物有关;在英国,每年用于植入物相关感染的费用达到1100万英镑。除了消耗巨大社会财富,还给病人带来巨大的痛苦,甚至导致截肢、死亡等严重后果。因此研制具有抗感染作用的内固定植入物,预防和治疗内植入物相关感染,具有重要的意义。
过去的三十多年中,在一系列新的生物相容性较好的无机材料和有机高分子材料基础上逐渐发展起来一种新型局部给药方式--抗生素缓释系统,在治疗开放性骨折、骨髓炎和感染性骨缺损等方面有着广泛的应用前景。万古霉素属于糖肽类抗生素,对各种革兰氏阳性菌都具有高度抗菌活性,是目前治疗耐甲氧西林金葡菌(MRSA)和耐甲氧西林表皮葡萄球菌(MRSE)等所致重症感染的首选抗生素,在临床治疗学上占据重要地位。因此被认为是较理想的的局部应用的抗生素之一;聚-DL-乳酸(PDLLA)是具有良好生物相容性、可降解吸收性、良好的力学稳定性和良好的成骨诱导能力,被广泛应用于生物医学工程领域,尤其是在药物控制释放体系中,它在植入物表面通过水解作用而降解,需要3~6个月时间,最终降解产物是CO2和H2O,中间代谢产物乳酸也是体内正常糖代谢产物,其降解产物最终通过柠檬酸循环而代谢,因此在体内不会对人体产生明显的不良影响;羟基磷灰石(HA)也具有良好的生物相容性和可降解吸收性,骨外科上可用作内固定材料。若能将PDLLA或HA与内固定材料及抗生素结合起来,制作出载抗生素缓释系统,从而在病灶局部释放出抗生素以使得治疗开放性骨折和火器伤等所致感染的效果能够得到大大提高。
目的
以PDLLA为载体,采用solvent casting技术,研制出载万古霉素-PDLLA钢板;同时以HA为载体,采用仿生溶液法研制出载万古霉素-HA钢板,通过体内体外试验的研究,希望此两种钢板在骨折愈合过程中能够在局部发挥强力的抗感染性能,起到预防和治疗感染的双重作用,为开放性骨折和火器伤提供早期的较好的治疗措施。
方法
第一部分:
实验一:1.采用solvent casting技术制作载万古霉素-PDLLA钢板。2.通过扫描电镜对载万古霉素-PDLLA钢板涂层进行观察。3.测定载万古霉素-PDLLA钢板涂层中万古霉素的含量及在20ml磷酸盐缓冲液中不同时相点的万古霉素释放浓度,了解该钢板涂层中万古霉素的释放动力学过程。4.将载万古霉素-PDLLA钢板置入均匀涂有1.5×108 CFU/ml金黄色葡萄球菌(S. aureus)的Mueller-Hinton(MH)琼脂培养皿中培养,于不同时相点测量抑菌圈大小,检测其对金黄色葡萄球菌的抑制作用。
实验二:参考医疗器械生物学评价标准,通过热原试验,溶血试验,肌肉植入试验,细胞毒性试验等来检测载万古霉素-PDLLA钢板的生物相容性。
第二部分:1.采用仿生溶液(Simulated body fluid ,SBF)技术,以羟基磷灰石(HA)为载体,制作载万古霉素-HA钢板。2.通过扫描电镜、X射线能谱仪及傅里叶变换红外检测仪等对载万古霉素-HA钢板表面涂层进行检测。3.将载万古霉素-HA钢板置入均匀涂有1.5×108 CFU/ml金黄色葡萄球菌的MH琼脂培养皿中培养,于不同时相点测量抑菌圈大小,检测其对金黄色葡萄球菌的抑制作用。
第三部分:1.采用solvent casting技术制备载万古霉素-PDLLA钢板。2.制备新西兰大白兔胫骨中段横断骨折金黄色葡萄球菌污染模型,分别置入载万古霉素-PDLLA钢板和普通裸钢板,在骨折断端注射1×106CFU/ml金黄色葡萄球菌,通过不同时相点的新西兰大白兔的体重、体温变化,白细胞、血沉和C反应蛋白检测,病理组织学检测、X光片检测及周围组织细菌培养等来比较两种钢板的抗感染效果。
结果
第一部分:
实验一:1.成功制备出载万古霉素-PDLLA钢板,扫描电镜观察显示在钢板表面获得了较均匀、致密的涂层,万古霉素分子以小颗粒状分布于PDLLA涂层中。2.体外释放试验显示:载万古霉素-PDLLA钢板具有良好的缓释作用,在磷酸盐缓冲液中持续释放万古霉素20天以上。3.抑菌试验证明:载万古霉素-PDLLA钢板对金黄色葡萄球菌具有超过15天的抑制作用。
实验二:载万古霉素-PDLLA钢板各项生物学指标均合格,其组织相容性、血液相容性良好,无细胞毒性,不含热原物质。
第二部分:1.成功制备出载万古霉素-羟基磷灰石钢板;2. SEM、EDX及FT-IR检测显示载万古霉素-HA钢板表面形成了均匀、致密的涂层,其结构为HA。2.体外抑菌试验证明:载万古霉素-HA钢板对金黄色葡萄球菌具有一定的抑制作用,第一天载万古霉素-HA钢板周围出现了明显的圆形抑菌圈,但第二天的抑菌圈却迅速缩小,第三天基本未见抑菌圈,显示其经过第一天的爆发性释放后,第二天释放的万古霉素已不能达到有效抑菌浓度。我们根据实验结果发现,载万古霉素-HA钢板抗生素释放太快,与临床上治疗感染需要的时间不相适应。可能与我们的制备技术等各种因素有一定关系。所以我们暂时取消了载万古霉素-HA钢板的进一步研究。
第三部分:载万古霉素-PDLLA钢板可以有效降低新西兰大白兔胫骨骨折金黄色葡萄球菌污染模型术后第1、3、7、14、28、56天静脉血中白细胞、血沉和C反应蛋白含量;对兔体温有一定影响,但对体重没有明显影响;X光片、病理学检查及细菌培养结果等显示可以有效降低新西兰大白兔胫骨骨折金黄色葡萄球菌污染模型的感染率。
结论
1.成功制备出了载万古霉素-PDLLA钢板,载万古霉素-PDLLA钢板的体外释放动力学稳定,并对金黄色葡萄球菌具有稳定的体外抑菌性能;载万古霉素-PDLLA钢板具有良好的生物相容性;载万古霉素-PDLLA钢板对新西兰大白兔胫骨骨折金黄色葡萄球菌污染模型具有明确的抗感染效果。
2.载万古霉素-HA钢板能有效的携载万古霉素,且保持了其抑菌活性,但其有效抑菌效果仅维持24h。
Background
As the report of AO in 2006 suggests,those patients with opened fractures are known to be at higher risk of infection ranged from 3~40% (the rate of infection in closed fractures is 1.5%). Up to 60% of open fractures are contaminated with bacteria at the time of injury . In wartime firearm injuries, serious tissue damage and pollution allow great quantities of bacteria to survive in the area (0.5 cm) around the wound. The infection rate of bone and soft tissue ranged from 25% to 40%, and even followed by adequate wound debridement. Maurer et al reported the rate of infection in open tibia fractures increased to greater than 30% when internal fixation was used. For instance, implant-associated infections account for nearly 50% of the estimated 2 million nosocomial infections in the United States per year. In Britain, the loss was 7-11 million pounds per year. Meanwhile, the infection raised the expense of patients and increased the suffering of the human body and psychology of patients. Infection can even have such severe consequences as death. Therefore, it would be clinically advantageous to develop an internal fixation that possesses anti-infection properties to prevent and cure implant infections.
During the past thirty years, a drug-delivery system was gradually developed on the basis of a series of original, fine biocompatibility inorganic material and organ-polymers. This system had a broad application perspective in the treatment directions of opened fracture, osteomyelitis and bone defects due to infection. Vancomycin (VCM) belongs to glycopeptide antibiotics. It has broad antimicrobial spectrum, covering most bacteria commonly involved in Gram-positive bacteria. Now it is the one of the top choice to cure severe infection which caused by MRSA or MRSE. And it is considered the one of the antibiotics for local application. Poly(D,L)-lactic acid (PDLLA) has excellent features with respect to implant-coating including high mechanical stability, good osteoinductive potential, biodegradability and excellent biocompatibility in vivo. The PDLLA coating is degraded by hydrolysis 3-6 months after implantation. The products of degradation are metabolized in the citric acid cycle. Otherwise, HA has excellent features with respect to implant-coating including biodegradability and excellent biocompatibility too. Because of these above mentioned reasons, PDLLA and HA can be used in orthopedic internal fixation. It is possible that the risk of infection can be reduced by developing an antiseptic surface coating for medical implants.
Objective
With PDLLA as a carrier, PDLLA coatings carrying VCM were prepared on the surface of titanium alloy plate substrates using solvent-casting technology. Meanwhile, HA coatings which carrying Vancomycin were prepared on the surface of titanium plate substrate using simulated body fluid technology with the HA as a carrier. Through vivo and vitro test, VCM-PDLLA loaded plates and VCM-HA loaded plates were expected to have dual effects of prophylaxis and cure infection in local and had a characteristic of fine therapeutic measure for opened fracture and firearm wound .
Methods
Part 1
Experiment 1: VCM-PDLLA loaded plates were prepared by solvent casting technology. To observe the coating of VCM-PDLLA loaded plates by SEM. The drug release profile of the plates were measured by immersing plates into 20ml PBS and measuring the content of VCM in different phase. The bacteriostatic activity to Staphylococcus aureus of the plates were evaluated by put the plates into Mueller-Hinton (MH) agar Petri dishes and the inhibition zones forming around the discs were measured in different phase.
Experiment 2: To consult the biological evaluation of medical devices, the biocompatibility of VCM-PDLLA loaded plates were investigated by pryogen test, hemolytic test, cytotoxic test, et al.
Part 2
VCM-HA loaded plates were prepared using simulated body fluid technology. VCM-HA loaded plates were detected by the test method of SEM, EDX and FT-IR. The bacteriostatic activity to Staphylococcus aureus of the plates were evaluated by put the plates into MH agar Petri dishes and the inhibition zones forming around the discs were measured in different phase.
Part 3
VCM-PDLLA loaded plates were inserted in model of rabits that the middle tibia were fracture and were stained with 1×106CFU/ml S. aureus. In different phase, WBC, CRP, ESR, et al were measured to evaluate the anti-infection effect of the plates.
Results
1. VCM-PDLLA loaded plates were obtained. Plates showed a sustained in vitro drug release character in the experiment, in which VCM released from the plate was sustained over 20 days. The in vitro inhibition of Staphylococcus aureus showed that the plates had an inhibitory effect on Staphylococcus aureus, and the antibacterial activity was maintained for at least 15 days. There were no toxicity for the VCM-PDLLA loaded plates, and the plates had good biocompatibility .
2. VCM-HA loaded coatings were prepared on the plates. The test of SEM, EDX and FT-IR indicated that the smooth and uniform coating was formed on the surface of the plates. The test of bacteriostasis indicated that obvious inhibition zone was appeared around the plate and it showed that VCM was successfully loaded on the coating. But in the next day the inhibition zone quickly contracted and in 3d the inhibition zone vanished. The result showed it could not achive the valid inhibitive concentration through the explosive release of the first day. According this, we think it may be related to various factor such as the preparative technique and determined to cancel the next study of VCM-HA loaded plates.
3. VCM-PDLLA loaded plates could effective cut down the content of WBC, ESR and CRP of the model of rabits that the middle tibia were fracture and were stained with S.aureus, and could affect the body temperature, but could not affect the body weight in different phase. X-ray, pathologic examine and bacterial culture showed the plates could effective cut down the infection rate of the model.
Conclusion
1. VCM-PDLLA loaded plates showed a sustained in vitro drug release character, and the plates had an stabile inhibitory effect on S.aureus in vivo. There was a good biocompatibility for the plates. The plates were effective at inhibiting infection in an model of rabits that the middle tibia were fracture and were stained with S. aureus.
2. VCM-HA loaded plates carried Vancomycin effectively and kept their bacteriostatic activity, but only sustained 24h.
引文
[1] Harris LG, Richards RG, Staphylococci and implant surfaces: a review. Injury, 2006, 37(2):3-14.
[2] European Antimicrobial Resistance Surveillance System Annual Report (EARSS) 2002.
[3] Maurer D J, Merkow R L, Gustilo R B. Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation. J Bone Joint Surg Am, 1989, 71(6):835-838.
[4] Checketts R, Otterburn M, MacEachern G. Pin track infection: definition, incidence and prevention. Int J Orthop Trauma. 1993; 3(3):16-18.
[5] Mahan J, Seligson D, Henry SL, et al. Factors in pin tract infections. Orthopedics.1991; 14(3):305-308.
[6] Hargreaves DG, Pajkos A, Deva AK, et al. The role of biofilm formation in percutaneous Kirschner-wire fixation of radial fractures. J Hand Surg Br. 2002; 27(4):365-368.
[7] Worlock P, Slack R, Harvey L, Mawhinney R. The prevention of infection in openfractures: an experimental study of the effect of fracture stability. Injury. 1994; 25(1):31-38.
[8] Trampuz A, ZimmerliW. Diagnosis and treatment of infections associated with fracture-fixation devices. Injury, Int. J. Care Injured,2006, 37(2):59-66.
[9] Periti P, Stringa G, Mini E. Comparative multicentertrial of teicoplanin versus cefazolin for antimicrobial prophylaxis in prosthetic joint implant surgery. Italian Study Group for Antimicrobial Prophylaxis in Orthopedic Surgery. Eur J Clin Microbiol Infect Dis. 1999,18(2):113-119.
[10] Anwar H,Costerton J W. Enhanced activity of combination of tobramycin and piperacillin for eradication of sessile biofilm cells of pseudomonas aeruginosa. Antimicrob Agents Chemother, 1990, 34(9): 1666-1671.
[11] Donlan RM. Biofilms: Microbial life on surfaces. Emerg Infect Dis, 2002, 8(9): 881-890.
[12] Stewart PS Costerton JW.Antibiotic resistance of bacteria in biofilms. Lancet,2001, 358(9276):135-138.
[13] Marc H, Gregor R. Microbial Biofilms: Their development and significance for medical device-related infections. J Clin Pharmacol, 1999, 39(9):887-898.
[14] Costerton JW,Cheung W,Geesey GG,et al. Bacterial biofilm in nature and disease. Ann Rev Microbiol,1987,41:435-464.
[15]小林宏行.细菌菌膜的基础与临床.中国临床药理学杂志, 1999, 15(4): 299-307.
[16] Gristina AG. Implant failure and the immuno-incompetent fibro-inflammatory zone. Clin Orthop,1994,(298):106-118.
[17] Garvin KL, Hanssen AD. Infection after total hip arthroplasty: past,present, and future. J Bone Joint Surg Am ,1995, 77(10):1576-1588.
[18] Gristina AG, Costerton JW. Bacterial adherence and the glycoalyx and their role in musculoskeletal infection.Orthop Clin \ North Am,1984,15(3):517-535.
[19] Mack D. The intercellular adhesion involved in biofilm accumulation of staphylococcus epidermidis is a linear beta-1,6-linked glucosaminoglycan;purification and structuralanalysis. J Bacterial,1996,178(2):175-181.
[20] YasudaH,Ajiki Y,Aoyama J, et al. Interaction between human polymorphonuclesr leucocytes and bacterial action of glycopeptide antibiotics. J Infect Dis, 1990, 161: 37.
[21] Blaser J, Vergeres P, Widmer Af,et al. In Vivo verification of in vitro model of antibiotic treatment of device related infection.Antimicrob Agent Chemother, 1995,39(5):1134-1139.
[22] Dietz FR,Koontz FP,Found EM, et al. The importance of positive bacterial cultures of specimens obtained during clean orthopaedic operations. J Bone Joint surg (Am),1991,73(8):1200-1207.
[23]吴宇黎,李晓华,钱齐荣,等.感染性人工关节生物膜中细胞外多粘质物质对抗生素的影响.中国矫形外科杂志,2002,10(10):980-981.
[24] Vikram HR,Buencamino RB,Aronin SL.Primary meningococcal arthritis in a prosthetic knee joint.J Infect,2001,42(4):279-281.
[25]黄云超,张良,林兴,等.胞外黏质物在心血管材料表面细菌生物膜形成中的作用.中华医院感染学杂志,2006,16(3):292-295.
[26] Radin S, El-Bassyouni G, Vresilovic EJ, et a1. In vivo tissue response to resorbable silica xerogels as controlled release materials. Biomaterials. 2005; 9(26): 1043-1052.
[27] Schmidmaier G, Lucke M, Wildemann B, et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury. 2006; 37(2): 105-112.
[28] Radin S, Ducheyne P. Controlled release of vancomycin from thin sol–gel films on titanium alloy fracture plate material. Biomaterials. 2007; 28(9):1721-1729.
[29] Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg, 1970,41(11):511-515.
[30] Wahiling H,BuchholzHW. Experimental ang clinical studieson the release of gentamycin from bone cement. Chirurg,1972,43(10): 441-445.
[31] Wahiling H,Hameister W,Grieben A. Releease of gentamyicn forom potymethyl methacrylate I.Experimental in-vitro tests.Langenbecks Arch,Chir,1972,331(3): 169-192.
[32] Vidal J,Allieu Y.Utilisation de metacrylate de methyle pour comblerles cavites d’osteite entendue desmembers. Rev Chir Orthop,1969,55(6):158.
[33] Klemm K W. Antibiotic Bead Chains. Clinical Orthopaedics and Related Research,1993,295(10): 63-76.
[34] Diefenbeck M, Mückley T, Hofmann GO. Prophylaxis and treatment ofimplant-related infections by local application of antibiotics. Injury, 2006, 37(suppl 2): 95-104.
[35] Darouiche RO, Farmer J, Chaput C et al. Anti-infective efficacy of antiseptic-coated intramedullary nail. J BoneJoint Surg Am, 1998,80(9):1336-1340.
[36] Schierholz JM, Rump A, Pulverer G. New antiinfectious biomaterials. ciprofloxacin containing polyurethanes as potential drug delivery systems to prevent foreign-body infection. Arzneimittelforschung, 1997, 47(1): 70.
[37] Gollwitzer H,Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. JAC, 2003, 51(3):585-591.
[38]王爱民,王子明,唐桂阳,等.万古霉素骨水泥在感染人工髋关节翻修中作用的实验研究与临床观察.中华创伤骨科杂志,2004,6(6):603-607.
[39] [Schmidmaier G, Wildemann B, Stemberger A, et al.Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res, Applied Biomat, 2001,58(4):449-455.
[40] Schmidmaier G, Wildemann B, Bail H, et al. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-?1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone, 2001, 28(4):341-350.
[41] Tengvall P, Lunfsytom I. Physico-chemical consideration of titanium as a biomaterial. Clin Mater, 1992, 9 (1):115-134.
[1] Radin S, Ducheyne P. Controlled release of vancomycin from thin sol–gel films on titanium alloy fracture plate material. Biomaterials, 2007, 28(9):1721-1729.
[2] Radin S, El-Bassyouni G, Vresilovic EJ, et a1. In vivo tissue response to resorbable silica xerogels as controlled release materials. Biomaterials, 2005, 9(26): 1043-1052.
[3] Schmidmaier G, Lucke M, Wildemann B, et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury. 2006, 37(2): 105-112.
[4]王爱民,王子明,唐桂阳,等.万古霉素骨水泥在感染人工髋关节翻修中作用的实验研究与临床观察.中华创伤骨科杂志, 2004, 6(6): 603-607.
[5] Schmidmaier G, Wildemann B, Stemberger A, et al.Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res, Applied Biomat, 2001, 58(4): 449-455.
[6] Schmidmaier G, Wildemann B, Bail H, et al. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-?1) from a biodegradablepoly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone, 2001, 28(4): 341-350.
[7] Gollwitzer H,Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. JAC, 2003, 51(3):585-591.
[8] Harris LG, Richards RG, Staphylococci and implant surfaces: a review. Injury, 2006, 37(2):3-14.
[9] Seligson D, Klemm K. Adult post traumatic osteomyelitis of the tibial diaphysis of the tibial shaft. Clin Orthop Relat Res, 1999, 360:30-36.
[10] European Antimicrobial Resistance Surveillance System Annual Report (EARSS) 2002.
[11] Maurer D J, Merkow R L, Gustilo R B. Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation. J Bone Joint Surg Am, 1989, 71(6):835-838.
[12] Checketts R, Otterburn M, MacEachern G. Pin track infection: definition, incidence and prevention. Int J Orthop Trauma. 1993; 3(3):16-18.
[13] Mahan J, Seligson D, Henry SL, et al. Factors in pin tract infections. Orthopedics.1991; 14(3):305-308.
[14] Hargreaves DG, Pajkos A, Deva AK, et al. The role of biofilm formation in percutaneous Kirschner-wire fixation of radial fractures. J Hand Surg Br. 2002; 27(4):365-368.
[15] Worlock P, Slack R, Harvey L, Mawhinney R. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury. 1994; 25(1):31-38.
[16] Darouiche RO.Treatment of infections associated with surgical implants. N Engl J Med, 2004, 350(14):1422-1429.
[17] Flcok JI, Brennan F. Antibodies that blcok adherence of to fibornectin. Letter,1999, 7(4):140-141.
[18]张德立,陈立福.骨科医院感染病原菌及药敏结果分析.中华医院感染学杂志,2001,11(2): 147-148.
[19]王化芬,王晓军,于茜,等.骨科感染病原菌谱与抗菌谱3年报告.中华矫形外科杂志,2007, 15(4): 313-315.
[20]张俊,屠重棋.骨科感染与抗菌谱改变的相关研究.华西医学, 2005, 20(1): 61-62.
[21]唐良华,王爱民,杜全印,等,四肢骨折内固定术后感染的细菌分布,耐药分析和防治措施,四川医学,2008, 29(6): 679-682.
[22] von Eiff C, Proctor RA, Peters G. Coagulase-negative staphylococci. Pathogens have major role in nosocomial infections. Postgrad Med,2001,110(4):63-76.
[23] Barth E, Myrvik QM, Wagner W, etal.In vitro and in vivo comparative colonization of Staphylococcus aureus and Staphylococcus epidermidis on orthopaedic implant materials. Biomaterials,1989,10(5):325-328.
[24] von Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase- negative staphylococci. Lancet Infect Dis,2002, 2(11):677-685.
[25] Bagnoa A, Genovesea M, Luchinia A,et al. Contact prolometry and correspondence analysis to correlate surface properties and cell adhesion in vitro of uncoated and coated Ti and Ti6Al4V disks. Biomaterials, 2004, 25(12): 2437-2445.
[26] Gristina AG. Implant failure and the immuno-incompetent fibro-inflammatory zone. Clin Orthop,1994,(298):106-118.
[27] Garvin KL, Hanssen AD. Infection after total hip arthroplasty: past,present, and future. J Bone Joint Surg Am ,1995, 77(10):1576-1588.
[28] Costerton JW.Introduction to biofilm.Int J Antimicrob Agents,1999,11:217-221.
[29] Anwar H,Costerton J W. Enhanced activity of combination of tobramycin and piperacillin
[30] Donlan RM. Biofilms: Microbial life on surfaces. Emerg Infect Dis, 2002, 8(9): 881-890.
[31] Stewart PS Costerton JW.Antibiotic resistance of bacteria in biofilms. Lancet,2001, 358(9276):135-138.
[32] Marc H, Gregor R. Microbial Biofilms: Their development and significance for medical device-related infections. J Clin Pharmacol, 1999, 39(9):887-898.
[33] Costerton JW,Cheung W,Geesey GG,et al. Bacterial biofilm in nature and disease. Ann Rev Microbiol,1987,41:435-464.
[34]小林宏行.细菌菌膜的基础与临床.中国临床药理学杂志, 1999, 15(4): 299-307.
[35] Cramton SE, Gerke C, Schnell NF, et al.The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun,1999,67(10): 5427-5433.
[36] Parnham MJ.Immunomolulatory effects of antimicrobials in the therapy respiralory tract infection. Curr Opin Infect Dis, 2005,18(2):125-131.
[37]董荔,何礼贤,胡必杰,等.阿奇霉素对生物膜铜绿假单胞菌的头孢他啶敏感性的作用.中国抗生素杂态,2004,29(6):366-370.
[38]李建华,宋丰贵.细菌生物膜形成与细菌耐药机制研究进展.中国新药与临床杂志,2008,27(1):70-73.
[39] Jones MN.Use of liposomes to deliver to bacterial biofilms. Methods Enzymol, 2005, 391:211-218.
[40] Loiselle M, Andrson KW.The use of cellulase in inhibiting biofilm formlation from organisms commonly found on medical implants. Biofouling. 2003,19(2):77-85.
[41]贾鸣,胡晓梅,胡福泉.细菌生物被膜的耐药机制及控制策略.生命的化学,2008, 28(3):315-317.
[42] Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg, 1970,41(11):511-515.
[43] Charnley J . Acrylic cement in orthopedic surgery.Edinburgh and London: E&S Livingstone, 1970:118-125.
[44] Wahiling H,BuchholzHW. Experimental ang clinical studieson the release of gentamycin from bone cement. Chirurg,1972,43(10): 441-445.
[45] Wahiling H,Hameister W,Grieben A. Releease of gentamyicn forom potymethyl methacrylate I.Experimental in-vitro tests.Langenbecks Arch Chir, 1972, 331(3): 169-192.
[46] Klemm K W. Antibiotic Bead Chains. Clinical Orthopaedics and Related Research,1993,295(10): 63-76.
[47] Haydon RC, Blaha D J,Mancinelli C,et al. AudiometricThresholds in osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads. Clinical Orthopaedics and Related Research,1993,295: 43-46.
[48] CalhounJH, Henry SL, Anger DM,et al. The treatment of infected nonunions with gentamicin-polymenthylmethacrylate antibiotic beads. Clinical Orthopaedics and Related Research,1993,295:23-27.
[49] Lindsey RW, Probe R, MiclauT,et al. The effects of antibiotic-impregnated autogeneic cancellous bone graft on bone healing. Clinical Orthopaedics and Related Research,1993,291: 303-312.
[50] K?licke T, Schierholz J, Schlegel U, et al. Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants: An in vitro and in vivo study. J Orthop Res , 2006, 24(8):1622-1640.
[51] Darouiche RO, Farmer J, Chaput C,et al. Anti-infective efficacy of antiseptic-coated intramedullary nail. J BoneJoint Surg Am, 1998, 80(9): 1336-1340.
[52] Hutmacher D, Hurzeler MB, Schliephake H. A review of material properties of biodegradable and bioresorbable polymers and devices for GTR and GBR applications. Int J Oral Maxillofac Implants, 1996, 11(5): 667-678.
[1] Gollwitzer H,Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. JAC, 2003, 51(3):585-591.
[2] Biological evaluation of medical devices -Part 11: Tests for systemic toxicity(ISO 10993-11: 1993)[医疗器械生物学评价-第11部分:全身毒性试验.中华人民共和国国家标准GB/T16886.11-1997].
[3] Biological evaluation of medical devices-Part 4: Selection of tests for interactions with blood(ISO 10993-4: 2002)[医疗器械生物学评价-第4部分:与血液相互作用试验选择.中华人民共和国国家标准GB/T 16886.4-2003].
[4] Biological evaluation of medical devices-Part 6:Tests for local effects after implantation(ISO 10993-6:1994)[医疗器械生物学评价标准《国标—生物学评价》第6部分:植入后局部反应实验GB/T16886·6-1997].
[5] Biological evaluation of medical devices-Part 5: Tests for in vitro cytotoxicity(ISO 10993-5: 1999)[医疗器械生物学评价-第5部分:体外细胞毒性试验.中华人民共和国国家标准GB/T 16886.5-2003].
[6]裴国献,魏宽海,金丹.组织工程学实验技术,北京:人民军医出版社,2006,176-177.
[7]贺亚敏,黄培林,吕晓迎.几种医用材料的细胞生物相容性评价的实验研究,东南大学学报(医学版),2003,22(2):75-79.
[8]司徒镇强,吴军正.细胞培养,第1版,西安:世界图书出版公司,2004:250-251.
[1] Kokubo T,Takadama H. How useful is SBF in predicting in vivo bone bioactivity. Biomaterials 2006,27(15):2907-2915.
[2] Lim G K, Wang J,Ng S C,et al. Processing of Hydroxyapatite via Microe Mulsion and Emulsion Routes. Biomaterials. 1997,18(21):1433-1439.
[3] Richards RG,Harris LG,Schneider E,et al. Antiseptics and antibiotics on implants. Injury,2006,37(2):S113-S116.
[4] Tengvall P,Lunfsytom I. Physico-chemical consideration of titanium as a biomaterial. Clin.M ater,1992,9 (1):115-134.
[5] Schmidmaier G, Wildemann B, Stemberger A, et al.Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res, Applied Biomat, 2001,58(4):449-455.
[6] Li P,Groot K. Calcium phosphate formation within sol-gel prepared titaniain vitroandin vivo. J Biomed Mater Res,1993,27(12):1495.
[7] Wen HB,Liu Q,Wijn JR,et al. Preparation of bioactive microporous titanium surface by a new two-step chemical treatment. J Mater Sci:Mater Med,1998,9(3):121.
[8] Habibovic P, Jiaping L, Chantal M, et al.Biological perforrmance of uncoated and octacalcium phosphate2coated T i6A l4V. Biomaterials,2005,26(1):23-36.
[9]邓炜,王贻宁,蒋滔,等.仿生溶液法诱导钛表面形成钙磷涂层的研究.生物医学工程学杂志,2002,19(3):376.
[10]付涛,徐可为.仿生法沉积磷灰石层的研究进展.生物医学工程学杂志,2001,18(1): 116~118.
[1] Gollwitzer H,Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. JAC, 2003, 51(3):585-591.
[2]王爱民,王子明,唐桂阳,等.万古霉素骨水泥在感染人工髋关节翻修中作用的实验研究与临床观察.中华创伤骨科杂志,2004,6(6):603-607.
[3] Scott CP, Higham PA, Dumbleton JH. Effectiveness of bone cement containing tobramycin. J Bone Joint Surg Br , 1999,81(3):440-443.
[4] Trampuz A, Zimmerli W. Diagnosis and treatment of infections associated with fracture-fixation devices Injury, 2006,37(2): 59-66.
[5] Zych GA,Hutson JJJ. Diagnosis and management of infection after tibial intramedullary nailing. Clin Orthop,1995,(315):153?162.
[6] Gustilo RB, Merkow RL, Templeman D. The management of open fractures. J Bone Joint Surg Am,1990,72(2):299?304.
[7] Tunney MM, Patrick S, Curran MD, et al. Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J Clin Microbiol, 1999,37(10):3281-3290.
[8] Trampuz A, Piper KE, Hanssen AD, et al. Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint infection is associated with risk of contamination. J Clin Microbiol,2006 ,44(2):628-631.
[9] Trampuz A, Osmon DR, Hanssen AD, et al. Molecular and antibiofilm approaches to prosthetic joint infection. ClinOrthop, 2003, 414:69-88.
[10] Gristina AG, Costerton JW. Bacterial adherence to biomaterials and tissue. The significance of its role in clinical sepsis. J Bone Joint Surg Am, 1985, 67(2):264-273.
[11] Gristina AG, Oga M, Webb LX et al. Adherent bacterial colonization in the pathogenesis of osteomyelitis. Science, 1985,228(4702):990-993.
[12] Stemberger A, Grimm H, Bader F et al.Local treatment of bone and soft tissue infections with the collagengentamicin sponge. Eur J Surg.1997, 578 (Suppl):17-26.
[13] Hettfleisch J, Schottle H.Local preventive antibiotic treatment in intramedullary nailing with gentamycin impregnated biomaterials.Aktuelle Traumatol, 1993,23(2):68-71.
[14] Bagnoa A, Genovesea M, Luchinia A,et al. Contact prolometry and correspondence analysis to correlate surface properties and cell adhesion in vitro of uncoated and coated Ti and Ti6Al4V disks. Biomaterials, 2004, 25(12): 2437-2445.
[15] Jansen B, Peters G.Foreign body associated infection. J Antimicrob Chemother, 1993,32(Suppl A):69-75.
[16]中华人民共和国卫生部医发[2004]285号,抗菌药物临床应用指导原则,北京:中华人民共和国卫生部,2004.
[17] Zimmerli W, Trampuz A, Ochsner PE.Prosthetic-joint infections. N Engl J Med, 2004,351(16):1645-1654.
[18] Trebse R, Pisot V, Trampuz A.Treatment of infected retained implants. J Bone Joint Surg Br, 2005,87(2):249-256.
[19] Patzakis MJ. Management of open fracture wounds. Instr Course Lec t,1987,36:367-369.
[20] Cooney WP 3rd, Fitzgerald RH Jr, Dobyns JH, et al. Quantitative wound cultures in upper extremity trauma. J Trauma, 1982,22(2):112-117.
[21] Robson MC, Duke WF, Krizek TJ. Rapid bacterial screening in the treatment of civilian wounds. J Surg Res,1973,14(5):426-430.
[22] Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am,1974,56(3):532-541.
[23] Braun R, Enzler MA, Rittmann WW. A double-blind clinical trial of prophylactic cloxacillin in open fractures. J Orthop Trauma,1987,1(1):12-17.
[24] Sorger JI, Kirk PG, Ruhnke CJ, et al. Once daily, high dose versus divided, low dose gentamicin for open fractures. Clin Orthop,1999,366:197-204.
[25] Darouiche RO.Treatment of infections associated with surgical implants. N Engl J Med, 2004, 350(14):1422-1429.
[26] Zimmerli W, Widmer AF, Blatter M, et al.Role of rifampin for treatment of orthopedic implant-related staphylo Coccalinfections, arandomizedcontrolledtrial. Foreign-Body Infection (FBI) Study Group. JAMA, 1998,279(19):1537-1541.
[27] Tsukayama DT. Pathophysiology of posttraumatic osteomyelitis. Clin Orthop Relat Res,1999,(360):22-29.
[28] Bach AW, Hansen ST.Plates versus external fixation in severe open tibial shaft fractures. A randomized trial. ClinOrthop Relat Res, 1989,241:89-94.
[29] Worlock P, Slack R, Harvey L, et al. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury, 1994, 25(1):31-38.
[30] Ochsner PE, Baumgart F, Kohler G. Heat-induced segmental necrosis after reaming of one humeral and two tibial fractures with a narrow medullary canal. Injury, 1998,29(Suppl 2):1-10.
[31] Ochsner PE, GoseleA, Buess P.The value of intramedullary reaming in the treatment of chronic osteomyelitis of long bones. Arch Orthop Trauma Surg, 1990,109(6):341-347.
[32] Court-Brown CM, Keating JF, McQueen MM. Infection after intramedullary nailing of the tibia. J Bone Joint SurgBr, 1992,74(5):770-774.
[33] Court-Brown CM, Keating JF, McQueen MM. Infection after intramedullary nailing of the tibia. J Bone Joint SurgBr, 1992,74(5):770-774.
[34] Checketts R, Otterburn M, MacEachern G. Pin track infection: definition, incidence and prevention. Int J Orthop Trauma, 1993, 3(3):16-18.
[35] Grant AD, Atar D, Lehman WB. Pin care using the Ilizarov apparatus: recommended treatment plan in Kurgan,Russia. Bull Hosp Jt Dis, 1992,52(1):18-20.
[36] Green SA. Complications of external skeletal fixation.Clin Orthop Relat Res, 1983,180:109-116.
[37] Matthews LS, Green CA, Goldstein SA.The thermal effects of skeletal fixation-pin insertion in bone. J Bone Joint Surg Am, 1984,66(7):1077-1083.
[38] Burny F.The pin as a percutaneous implant. Orthopedics, 1984,7:610-615.
[39] Paley D, Jackson RW .Surgical scrub sponges as part of the traction apparatus: an alternative to pin site care to reduce pin track infections. Injury, 1985,16(9):605-606.
[40] Clifford RP, Lyons TJ, Webb JK.Complications of external fixation of open fractures of the tibia. Injury,1987,18(3):174-176.
[41] Hargreaves DG, Pajkos A, Deva AK, et al. The role of biofilm formation inpercutaneous Kirschner-wire fixation of radial fractures. J Hand Surg Br, 2002, 27(4):365-368.
[42] Parameswaran AD, Roberts CS, Seligson D, et al.Pintract infection with contemporary external fixation: how much of a problem? J Orthop Trauma,2003,17(7):503-507.
[43] Moroni A, Vannini F, Mosca M, et al.State of the art review: techniques to avoid pin loosening and infection in external fixation. J Orthop Trauma, 2002,16(3):189-195.
[44] Maurer DJ, Merkow RL, Gustilo RB .Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation. J Bone Joint Surg Am, 1989,71(6):835-838.
[45] Radin S, El-Bassyouni G, Vresilovic EJ, et a1. In vivo tissue response to resorbable silica xerogels as controlled release materials. Biomaterials. 2005; 9(26): 1043-1052.
[46] Schmidmaier G, Lucke M, Wildemann B, et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury. 2006; 37(2): 105-112.
[47] Radin S, Ducheyne P. Controlled release of vancomycin from thin sol–gel films on titanium alloy fracture plate material. Biomaterials. 2007; 28(9):1721-1729.
[48] Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg, 1970,41(11):511-515.
[49] Wahiling H,BuchholzHW. Experimental ang clinical studieson the release of gentamycin from bone cement. Chirurg,1972,43(10): 441-445.
[50] Wahiling H,Hameister W,Grieben A. Releease of gentamyicn forom potymethyl methacrylate I.Experimental in-vitro tests.Langenbecks Arch,Chir,1972,331(3): 169-192.
[51] Vidal J,Allieu Y.Utilisation de metacrylate de methyle pour comblerles cavites d’osteite entendue desmembers. Rev Chir Orthop,1969,55(6):158.
[52] Klemm K W. Antibiotic Bead Chains. Clinical Orthopaedics and Related Research,1993,295(10): 63-76.
[53] Diefenbeck M, Mückley T, Hofmann GO. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury, 2006, 37(suppl 2): 95-104.
[54] Garven KL,Hinrichs SH,Urban JA.Emerging antibiotic-resistant bacteria: their treatment in total joint arthroplasty. Clin Orthrop,1999,(369):110-123.
[55] Schmidmaier G, Wildemann B, Stemberger A, et al.Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res, Applied Biomat, 2001, 58(4): 449-455.
[56] Schmidmaier G, Wildemann B, Bail H, et al. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-?1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone, 2001, 28(4): 341-350.
[57] Hutmacher D, Hurzeler MB, Schliephake H. A review of material properties of biodegradable and bioresorbable polymers and devices for GTR and GBR applications. Int J Oral Maxillofac Implants, 1996, 11(5): 667-678.
[58]王永安,张玲,王永春. C-反应蛋白在外科感染中的应用.中华医院感染学杂志, 2000, 10(6): 440-441.
[59] DiCesare PE,ChangE, Preston CF,et al.Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty.J Bone JointSurgAm, 2005, 87(9): 1921-1927.
[60] BottnerF, WegnerA, W inkelmannW,etal.Interleukin-6, procalcitonin and TNF-alpha:markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Bt, 2007, 89:94-99.
[61]陈文彬,王友赤,王宏达,等.诊断学.人民卫生出版社,第五版,2002.
[62] Greidanus NV, Masri BA, Garbuz DS, et al. Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee arthroplasty.A prospective evaluation.J Bone JointSurgAm, 2007, 89: 1409-1416.
[63] Ochsner PE, Hailemariam S. Histology of osteosynthesis associated bone infection. Injury, Int Care Injured,2006,37(2):S49-S58.
[1] Harris LG, Geof RR. Staphylococci and implant surfaces:a review. Injury, 2006, 37(2): 3-l4.
[2] Darouiche RO. Treatment of infections associated with surgical implants. 2004,350(14): 1422-1429.
[3] Flcok JI,Brennan F. Antibodies that blcok adherence of to fibronectin. Letter,1999,7(4):140-141.
[4] Classen DC, Evans RS, Pestotnik SL,et al.The timing of prophylactic administation of antiobiotics and the risk of surgical wound infection.N Engl J med,1992,326(5):281–286.
[5] David C, Evans MD, Jonathan L, et al. Understanding the risk for infection in postoperative surgical wound.Comp Surg,1994,13(6):767.
[6] Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with palaces resins.Chirurg,1970,41(11):511-515.
[7] Vidal J, Allieu Y. Utilisation de metacrylate de methyle pour comblerles cavites d’osteite entendue desmembers. Rev Chir Orthop,1969,55(6):158.
[8] Klemm K W. Antibiotic Bead Chains. Clinical Orthopaedics and Related Research,1993,295(10): 63-76.
[9]王爱民,王子明,唐桂阳,等.万古霉素骨水泥在感染人工髋关节翻修中作用的实验研究与临床观察.中华创伤骨科杂志,2004,6(6):603-607.
[10] Radin S, El-Bassyouni G, Vresilovic EJ, et a1. In vivo tissue response to resorbable silica xerogels as controlled release materials. Biomaterials. 2005; 9(26): 1043-1052.
[11] Radin S, Ducheyne P. Controlled release of vancomycin from thin sol–gel films on titanium alloy fracture plate material. Biomaterials. 2007; 28(9):1721-1729.
[12] Thomas MT,Robert MU,Steven G,et al. Radiographic and histologic assessment of calcium sulfate in experimental animal models and clinical use as a resorbable bone-graft substitute,a bone-graft expander,and a method for local antibiotic delivery.J Bone Joint Surg, 2001,83(s2):8-17.
[13] Sasaki S , Ishii Y. Apatite cement containing antibiotics:efficacy in treating experimental osteomyelitis. J Orthop Sci,1999,4(5): 361-369.
[14] Athanasion KA, Singhal AR, Agrawal CM, et al. Degradation and release characteristics of biodegradable implants containing trypsin inhibitor. Clin Orthop, 1995, 315(6):272-281.
[15] Kevin L G, John AM, Dennis R, et al. Polylactide/polyglycolide antibiotic implants in the treatment of oseomyelitis. J Bone Joint Sur, 1994, 76 (10):1500-1506.
[16]万昌秀,段友容,吴刚,等. PEG的分子量对PPC缓释膜片体外动态释放速率影响的研究.四川大学学报(工程科学版),2000, 32(2): 51-54.
[17] Schmidmaier G, Lucke M, Wildemann B, et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury. 2006; 37(2): 105-112.
[18] Aoki H. Science and Medical Applications of Hydroxyapatite. JAAS. Printed in Tokyo, 1991: 1~20.
[19]孙梁,胡蕴玉,桑宏勋,等. RBX-庆大霉素药物释放系统的研制及体外释放实验.中国矫形外科杂志, 2000, 7(5): 448-452.
[20]俞玮,周勇,范清宇,等.阿霉素异体脱钙骨基质骨粒骨水泥的制备及体内释药实验.解放军医学杂志, 2002, 27(8): 683-684.
[21]李宝兴,张育敏,李春源,等.庆大霉素抗菌骨制备及体内外释放特性实验研究.中华创伤骨科杂志, 2004, 6(3):v293-296.
[22]韦岩.抗菌肽的研究进展和临床应用,菏泽医学专科学校学报, 2007, 19(1): 78.
[23] Warnke PH, Springer IN, Russo PAJ, et al. Innate immunity in human bone. Bone, 2006, 38(3): 400-408.
[1] Harris LG, Richards RG, Staphylococci and implant surfaces: a review. Injury, 2006, 37(2):3-14.
[2] European Antimicrobial Resistance Surveillance System Annual Report (EARSS) 2002.
[3] Maurer D J, Merkow R L, Gustilo R B. Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation. J Bone Joint Surg Am, 1989, 71(6):835-838.
[4] Checketts R, Otterburn M, MacEachern G. Pin track infection: definition, incidence and prevention. Int J Orthop Trauma. 1993; 3(3):16-18.
[5] Mahan J, Seligson D, Henry SL, et al. Factors in pin tract infections. Orthopedics.1991; 14(3):305-308.
[6] Hargreaves DG, Pajkos A, Deva AK, et al. The role of biofilm formation in percutaneous Kirschner-wire fixation of radial fractures. J Hand Surg Br. 2002; 27(4):365-368.
[7] Worlock P, Slack R, Harvey L, Mawhinney R. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury. 1994; 25(1):31-38.
[8] Darouiche RO.Treatment of infections associated with surgical implants. N Engl J Med, 2004, 350(14):1422-1429.
[9] Flcok JI, Brennan F. Antibodies that blcok adherence of to fibornectin. Letter,1999, 7(4):140-141.
[10]张德立,陈立福.骨科医院感染病原菌及药敏结果分析.中华医院感染学杂志, 2001,11(2): 147-148.
[11]王化芬,王晓军,于茜,等.骨科感染病原菌谱与抗菌谱3年报告.中华矫形外科杂志,2007, 15(4): 313-315.
[12]张俊,屠重棋.骨科感染与抗菌谱改变的相关研究.华西医学, 2005, 20(1): 61-62.
[13]唐良华,王爱民,杜全印,等,四肢骨折内固定术后感染的细菌分布,耐药分析和防治措施,四川医学,2008, 29(6): 679-682.
[14] von Eiff C, Proctor RA, Peters G. Coagulase-negative staphylococci. Pathogens have major role in nosocomial infections. Postgrad Med,2001,110(4):63-76.
[15] Barth E, Myrvik QM, Wagner W, etal.In vitro and in vivo comparative colonization of Staphylococcus aureus and Staphylococcus epidermidis on orthopaedic implant materials. Biomaterials,1989,10(5):325-328.
[16] von Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase- negative staphylococci. Lancet Infect Dis,2002, 2(11):677-685.
[17] Wilkinson BJ.Biology. Crossley KB, Archer GL (eds), The Staphylococci in Human Diseases. New York: Churchill Livingston, 1997:1-38.
[18] Kloos WE, Musselwhite MS. Distributionandpersistence of Staphylococcus andMicrococcus species and other aerobic bacteria on human skin. Appl Microbiol, 1975, 30 (3): 381-385.
[19] Elek S. Experimental staphylococcal infections in the skin of man. Ann NY Acad Sci, 1956,65(3):85-90.
[20] Waldvogel FA. Staphylococcus aureus (including toxic shock syndrome). Mandell GL, Douglas RG, Bennett JE (eds), Principles and practice of infectious disease 3rd ed. New York:Churchill Livingston, 1990:1489-1510.
[21] Central Public Health Laboratory. Surveillance of surgical site infection in English hospitals, UK. 2000:1997-1999.
[22] Fukatsu K, Saito H, Matsuda T, et al. Influences of type and duration of antimicrobial prophylaxis on an outbreak of methicillin-resistant Staphylococcus aureus and on the incidence of wound infection. Arch Surg, 1997, 132(12):1320-1325.
[23] Hiramatsu K. Vancomycin-resistant Staphylococcus aureus: a new model of antibiotic resistance. Lancet Infect Dis,2001,1(3):147-155.
[24] Herrmann M, Vaudaux PE, Pittet D, et al. Fibronectin,fibrinogen, and laminin act as mediators of adherence of clinical staphylococcal isolates to foreign material, J InfectDis, 1988,158(4):693-701.
[25] Gross M, Cramton SE, Gotz F, Peschel A. Key role of teichoic acid net charge in Staphylococcus aureus colonization of artificial surfaces. Infect Immun, 2001,69(5): 3423-3426.
[26] Cramton SE, Gerke C, Schnell NF, et al.The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun,1999,67(10): 5427-5433.
[27] Gotz F. Staphylococcus and biofilms. Mol Microbiol,2002,43(6):1367-1378.
[28] Mack D, Haeder M, Siemssen N, Laufs R.Association of biofilm production of coagulase-negative staphylococci with expression of a specific polysaccharide intercellular adhesin.J Infect Dis, 1996,174(4):881-884.
[29] Heilmann C, Schweitzer O, Gerke C, et al. Molecular basis of intercellular adhesion in the biofilm-forming Staphylococcus epidermidis. Mol Microbiol, 1996.20(5):1083-1091.
[30] Mack D, Riedewald J, Rohde H, et al. Essential functional role of the polysaccharide 108intercellular adhesin of Staphylococcus epidermidis in hemagglutination. Infect Immun,1999,67(2):1004-1008.
[31] Vuong C, Kocianova S, Voyich JM, et al. A crucial role for exopolysaccharide modification in bacterial biofilm formation, immune evasion, and virulence. J Biol Chem,2004,279(52):54881-54886.
[32] Hussain M, Becker K, von Eiff C, et al. Identification and characterization of a novel 38.5-Kilodalton cell surface protein of Staphylococcus aureus with extended-spectrum binding activity for extracellular matrix and plasma proteins.J Bacteriol, 2001.183(23):6778-6786.
[33] Trampuz A, ZimmerliW. Diagnosis and treatment of infections associated with fracture-fixation devices. Injury, Int. J. Care Injured,2006, 37(2):59-66.
[34] Periti P, Stringa G, Mini E. Comparative multicentertrial of teicoplanin versus cefazolin for antimicrobial prophylaxis in prosthetic joint implant surgery. Italian Study Group for Antimicrobial Prophylaxis in Orthopedic Surgery. Eur J Clin Microbiol Infect Dis. 1999,18(2):113-119.
[35] Anwar H,Costerton J W. Enhanced activity of combination of tobramycin and piperacillin
[36] Donlan RM. Biofilms: Microbial life on surfaces. Emerg Infect Dis, 2002, 8(9): 881-890.
[37] Stewart PS Costerton JW.Antibiotic resistance of bacteria in biofilms. Lancet,2001, 358(9276):135-138.
[38] Marc H, Gregor R. Microbial Biofilms: Their development and significance for medical device-related infections. J Clin Pharmacol, 1999, 39(9):887-898.
[39] Costerton JW,Cheung W,Geesey GG,et al. Bacterial biofilm in nature and disease. Ann Rev Microbiol,1987,41:435-464.
[40]小林宏行.细菌菌膜的基础与临床.中国临床药理学杂志, 1999, 15(4): 299-307.
[41] Gristina AG. Implant failure and the immuno-incompetent fibro-inflammatory zone. Clin Orthop,1994,(298):106-118.
[42] Garvin KL, Hanssen AD. Infection after total hip arthroplasty: past,present, and future. J Bone Joint Surg Am ,1995, 77(10):1576-1588.
[43] Gristina AG, Costerton JW. Bacterial adherence and the glycoalyx and their role inmusculoskeletal infection.Orthop Clin \ North Am,1984,15(3):517-535.
[44] Mack D. The intercellular adhesion involved in biofilm accumulation of staphylococcus epidermidis is a linear beta-1,6-linked glucosaminoglycan;purification and structuralanalysis. J Bacterial,1996,178(2):175-181.
[45] YasudaH,Ajiki Y,Aoyama J, et al. Interaction between human polymorphonuclesr leucocytes and bacterial action of glycopeptide antibiotics. J Infect Dis, 1990, 161: 37.
[46] Blaser J, Vergeres P, Widmer Af,et al. In Vivo verification of in vitro model of antibiotic treatment of device related infection.Antimicrob Agent Chemother, 1995,39(5):1134-1139.
[47] Dietz FR,Koontz FP,Found EM, et al. The importance of positive bacterial cultures of specimens obtained during clean orthopaedic operations. J Bone Joint surg(Am),1991,73(8):1200-1207.
[48]吴宇黎,李晓华,钱齐荣,等.感染性人工关节生物膜中细胞外多粘质物质对抗生素的影响.中国矫形外科杂志,2002,10(10):980-981.
[49] Vikram HR,Buencamino RB,Aronin SL.Primary meningococcal arthritis in a prosthetic knee joint.J Infect,2001,42(4):279-281.
[50]黄云超,张良,林兴,等.胞外黏质物在心血管材料表面细菌生物膜形成中的作用.中华医院感染学杂志,2006,16(3):292-295.
[51] Zych GA,Hutson JJJ. Diagnosis and management of infection after tibial intramedullary nailing. Clin Orthop,1995,(315):153?162.
[52] Gustilo RB, Merkow RL, Templeman D. The management of open fractures. J Bone Joint Surg Am,1990,72(2):299?304.
[53] Tunney MM, Patrick S, Curran MD, et al. Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J Clin Microbiol, 1999,37(10):3281-3290.
[54] Trampuz A, Piper KE, Hanssen AD, et al. Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint infection is associated with risk of contamination. J Clin Microbiol,2006 ,44(2):628-631.
[55] Trampuz A, Osmon DR, Hanssen AD, et al. Molecular and antibiofilm approaches to prosthetic joint infection. ClinOrthop, 2003, 414:69-88.
[56] Gristina AG, Costerton JW. Bacterial adherence to biomaterials and tissue. The 110significance of its role in clinical sepsis. J Bone Joint Surg Am, 1985, 67(2):264-273.
[57] Gristina AG, Oga M, Webb LX et al. Adherent bacterial colonization in the pathogenesis of osteomyelitis. Science, 1985,228(4702):990-993.
[58] Stemberger A, Grimm H, Bader F et al.Local treatment of bone and soft tissue infections with the collagengentamicin sponge. Eur J Surg.1997, 578 (Suppl):17-26.
[59] Hettfleisch J, Schottle H.Local preventive antibiotic treatment in intramedullary nailing with gentamycin impregnated biomaterials.Aktuelle Traumatol, 1993,23(2):68-71.
[60] Bagnoa A, Genovesea M, Luchinia A,et al. Contact prolometry and correspondence analysis to correlate surface properties and cell adhesion in vitro of uncoated and coated Ti and Ti6Al4V disks. Biomaterials, 2004, 25(12): 2437-2445.
[61] Jansen B, Peters G.Foreign body associated infection. J Antimicrob Chemother, 1993,32(Suppl A):69-75.
[62]中华人民共和国卫生部医发[2004]285号,抗菌药物临床应用指导原则,北京:中华人民共和国卫生部,2004.
[63] Zimmerli W, Trampuz A, Ochsner PE.Prosthetic-joint infections. N Engl J Med, 2004,351(16):1645-1654.
[64] Trebse R, Pisot V, Trampuz A.Treatment of infected retained implants. J Bone Joint Surg Br, 2005,87(2):249-256.
[65] Patzakis MJ. Management of open fracture wounds. Instr Course Lect,1987,36:367-369.
[66] Cooney WP 3rd, Fitzgerald RH Jr, Dobyns JH, et al. Quantitative wound cultures in upper extremity trauma. J Trauma, 1982,22(2):112-117.
[67] Robson MC, Duke WF, Krizek TJ. Rapid bacterial screening in the treatment of civilian wounds. J Surg Res,1973,14(5):426-430.
[68] Patzakis MJ, Harvey JP Jr, Ivler D. The role of antibiotics in the management of open fractures. J Bone Joint Surg Am,1974,56(3):532-541.
[69] Braun R, Enzler MA, Rittmann WW. A double-blind clinical trial of prophylactic cloxacillin in open fractures. J Orthop Trauma,1987,1(1):12-17.
[70] Sorger JI, Kirk PG, Ruhnke CJ, et al. Once daily, high dose versus divided, low dose gentamicin for open fractures. Clin Orthop,1999,366:197-204.
[71] Gustillo RB, Management of Open Fractures and Their Complications. Instr CourseLect,1982,31:18-29.
[72] Tetsworth K, Cierny G 3rd. Osteomyelitis debridement techniques. Clin Orthop,1999,360:87-96.
[73] Edlich RF, Rodeheaver GT, Morgan RF, et al. Principles of emergency wound management. Ann Emerg Med,1988,17(12):1284-1302.
[74] Olson SA. Open fractures of the tibial shaft. J Bone Joint Surg Am ,1996,78:1428-1437.
[75] Edwards CC, Simmons SC, Browner BD, et al.Severe open tibial fractures: results treating 202 injuries with external fixation. Clin Orthop,1988,230:98-115.
[76] Darouiche RO.Treatment of infections associated with surgical implants. N Engl J Med, 2004, 350(14):1422-1429.
[77] Zimmerli W, Widmer AF, Blatter M, et al.Role of rifampin for treatment of orthopedic implant-related staphylo Coccalinfections, arandomizedcontrolledtrial. Foreign-Body Infection (FBI) Study Group. JAMA, 1998,279(19):1537-1541.
[78] Tsukayama DT. Pathophysiology of posttraumatic osteomyelitis. Clin Orthop Relat Res,1999,(360):22-29.
[79] Bach AW, Hansen ST.Plates versus external fixation in severe open tibial shaft fractures. A randomized trial. ClinOrthop Relat Res, 1989,241:89-94.
[80] Worlock P, Slack R, Harvey L, et al. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury, 1994, 25(1):31-38.
[81] Ochsner PE, Baumgart F, Kohler G. Heat-induced segmental necrosis after reaming of one humeral and two tibial fractures with a narrow medullary canal. Injury, 1998,29(Suppl 2):1-10.
[82] Ochsner PE, GoseleA, Buess P.The value of intramedullary reaming in the treatment of chronic osteomyelitis of long bones. Arch Orthop Trauma Surg, 1990,109(6):341-347.
[83] Court-Brown CM, Keating JF, McQueen MM. Infection after intramedullary nailing of the tibia. J Bone Joint SurgBr, 1992,74(5):770-774.
[84] Checketts R, Otterburn M, MacEachern G. Pin track infection: definition, incidence and prevention. Int J Orthop Trauma, 1993, 3(3):16-18.
[85] Grant AD, Atar D, Lehman WB. Pin care using the Ilizarov apparatus: recommended treatment plan in Kurgan,Russia. Bull Hosp Jt Dis, 1992,52(1):18-20. 112
[86] Green SA. Complications of external skeletal fixation.Clin Orthop Relat Res, 1983,180:109-116.
[87] Matthews LS, Green CA, Goldstein SA.The thermal effects of skeletal fixation-pin insertion in bone. J Bone Joint Surg Am, 1984,66(7):1077-1083.
[88] Burny F.The pin as a percutaneous implant. Orthopedics, 1984,7:610-615.
[89] Paley D, Jackson RW .Surgical scrub sponges as part of the traction apparatus: an alternative to pin site care to reduce pin track infections. Injury, 1985,16(9):605-606.
[90] Clifford RP, Lyons TJ, Webb JK.Complications of external fixation of open fractures of the tibia. Injury,1987,18(3):174-176.
[91] Hargreaves DG, Pajkos A, Deva AK, et al. The role of biofilm formation in percutaneous Kirschner-wire fixation of radial fractures. J Hand Surg Br, 2002, 27(4):365-368.
[92] Parameswaran AD, Roberts CS, Seligson D, et al.Pintract infection with contemporary external fixation: how much of a problem? J Orthop Trauma,2003,17(7):503-507.
[93] Moroni A, Vannini F, Mosca M, et al.State of the art review: techniques to avoid pin loosening and infection in external fixation. J Orthop Trauma, 2002,16(3):189-195.
[94] Parnham MJ.Immunomolulatory effects of antimicrobials in the therapy respiralory tract infection. Curr Opin Infect Dis, 2005,18(2):125-131.
[95]董荔,何礼贤,胡必杰,等.阿奇霉素对生物膜铜绿假单胞菌的头孢他啶敏感性的作用.中国抗生素杂态,2004,29(6):366-370.
[96]李建华,宋丰贵.细菌生物膜形成与细菌耐药机制研究进展.中国新药与临床杂志,2008,27(1):70-73.
[97] Jones MN.Use of liposomes to deliver to bacterial biofilms. Methods Enzymol, 2005, 391:211-218.
[98] Loiselle M, Andrson KW.The use of cellulase in inhibiting biofilm formlation from organisms commonly found on medical implants. Biofouling. 2003,19(2):77-85.
[99]贾鸣,胡晓梅,胡福泉.细菌生物被膜的耐药机制及控制策略.生命的化学,2008, 28(3):315-317.
[100] Lange R, Luthen F, Beck U, et al.Cell-extracellular matrix interaction and physico-chemical characteristics of titanium surfaces depend on the roughness of the material.Biomol Eng, 2002,19(2-6):255-261.
[101] Harris LG, Tosatti S, Wieland M, et al.Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(L-lysine)-grafted-poly(ethylene glycol) copolymers. Biomaterials, 2004, 25(18): 4135-4148.
[102] Quirynen M, Bollen CM.The influence of surface roughness and surface-free energy on supra- and subgingival plaque formation in man. A review of the literature. J Clin Periodontol, 1995,22(1):1-14.
[103] Meredith DO, Eschbach L, Wood MA, et al.Human fibroblast reactions to standard and electropolished titanium and electropolished stainless steel. J Biomed Mater Res A, 2005,75(3): 541-555.
[104] Harris LG, Richards RG.Staphylococcus aureus adhesion to different treated titanium surfaces. J Mater Sci MaterMed, 2004,15(4):311-314.
[105] Nagaoka S, Kawakami H. Inhibition of bacterial adhesion and biofilm formation by a heparinized hydrophilic polymer. ASAIO J, 1995,41(3):M365.
[106] Kinnari TJ, Peltonen LI, Kuusela P, et al. Bacterial adherence to titanium surface coated with human serum albumin. Otol Neurotol, 2005,26(3):380-384.
[107] Mori Y, Nagaoka S, Takiuchi H, et al. A new antithrombogenic material with long polyethyleneoxide chains. TransAm Soc Artif Intern Organs, 1982, 28:459-63.
[108] Ruiz L, Fine E, Voros J, et al.Phosphorylcholine-containing polyurethanes for the control of protein adsorption and cell. J Biomater Sci Polym Ed, 1999,10(9):931-55.
[109] Galliani S, Viot M, Cremieux A,et al.Early adhesion of bacteremic strains of Staphylococcus epidermidis to polystyrene: influence of hydrophobicity, slime production, plasma, albumin, fibrinogen, and fibronectin.J Lab Clin Med, 1994,123(5): 685-692.
[110] Pascual A, Fleer A, Westerdaal N, et al. Modulation of adherence of coagulase-negative staphylococci to Teflon catheters in vitro. Eur J Clin Microbiol, 1986,5(5):518-522.
[111] Dexter SJ, Pearson RG, Davies MC, et al. A comparison of the adhesion of mammalian cells and Staphylococcus epidermidis on fibronectin-modified polymer surfaces.J Biomed Mater Res, 2001,56(2):222-227.
[112] PavesioA, Renier D, Cassinelli C, et al.Anti-adhesive surfaces through hyaluronancoatings. Med Device Technol, 1997,8(7):20-27.
[113] Radin S, El-Bassyouni G, Vresilovic EJ, et a1. In vivo tissue response to resorbable silica xerogels as controlled release materials. Biomaterials. 2005; 9(26): 1043-1052.
[114] Schmidmaier G, Lucke M, Wildemann B, et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury. 2006; 37(2): 105-112.
[115] Radin S, Ducheyne P. Controlled release of vancomycin from thin sol–gel films on titanium alloy fracture plate material. Biomaterials. 2007; 28(9):1721-1729.
[116] Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg, 1970,41(11):511-515.
[117] Wahiling H,BuchholzHW. Experimental ang clinical studieson the release of gentamycin from bone cement. Chirurg,1972,43(10): 441-445.
[118] Wahiling H,Hameister W,Grieben A. Releease of gentamyicn forom potymethyl methacrylate I.Experimental in-vitro tests.Langenbecks Arch,Chir,1972,331(3): 169-192.
[119] Vidal J,Allieu Y.Utilisation de metacrylate de methyle pour comblerles cavites d’osteite entendue desmembers. Rev Chir Orthop,1969,55(6):158.
[120] Klemm K W. Antibiotic Bead Chains. Clinical Orthopaedics and Related Research,1993,295(10): 63-76.
[121] Diefenbeck M, Mückley T, Hofmann GO. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury, 2006, 37(suppl 2): 95-104.
[122] Gollwitzer H,Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. JAC, 2003, 51(3):585-591.
[123]王爱民,王子明,唐桂阳,等.万古霉素骨水泥在感染人工髋关节翻修中作用的实验研究与临床观察.中华创伤骨科杂志,2004,6(6):603-607.
[124] Ostermann PA, Henry SL, Seligson D. The role of local antibiotic therapy in the management of compound fractures.Clin Orthop Relat Res, 1993,295:102-111.
[125] Eklund AM, Valtonen M, Werkkala KA. Prophylaxis of sternal wound infections with gentamicin-collagen implant:randomized controlled study in cardiac surgery. J HospInfect, 2005,59(2):108-112.
[126] Friberg O, Svedjeholm R, Soderquist B,et al. Local gentamicin reduces sternal wound infections after cardiac surgery: a randomised controlled trial. Ann Thorac Surg, 2005,79(1):153-162.
[127] SteinerH, HultmarkD, Engstrom A,et al. Sequence and specificity of two antibacteria.l proteins in sect immunity.Nature, 1981,292(5820): 246-251.
[128] Textor M, Tosatti S, Wieland M,et al. Use of molecular assembly techniques for tailoring the chemical properties on smooth and rough titanium surfaces. Ellingson JE, Lyngstadaas SP (eds), Bio-implant interface: improving biomaterials and tissue reaction, CRC Press, 2003,341-366.
[129] VandeVondele S, Voros J, Hubbell JA. RGD-grafted poly-L- lysine-graft- (polyethylene glycol) copolymers block non-specific protein adsorption while promoting cell adhesion. Biotechnol Bioeng, 2003, 82(7):784-790.
[130] PavesioA, Renier D, Cassinelli C, et al.Anti-adhesive surfaces through hyaluronan coatings. Med Device Technol, 1997,8(7):20-27.
[1] Bauer TW, Schils J. The pathology of total joint arthroplasty.I. Mechanisms of implant fixation. Skeletal Radiol. 1999; 28(8):423-432.
[2] Bauer TW, Schils J. The pathology of total joint arthroplasty.II. Mechanisms of implant failure. Skeletal Radiol. 1999; 28(9):483-497.
[3] Periti P, Mini E, Mosconi G. Antimicrobial prophylaxis in orthopaedic surgery: the role of teicoplanin. J Antimicrob Chemother. 1998; 41(3):329-340.
[4] Periti P, Stringa G, Mini E. Comparative multicenter trial of teicoplanin versus cefazolin for antimicrobial prophylaxis in prosthetic joint implant surgery. Italian Study Group for Antimicrobial Prophylaxis in Orthopedic Surgery. Eur J Clin Microbiol Infect Dis. 1999; 18(2):113-119.
[5] Sugarman B, Young EJ. Infections associated with prosthetic devices: magnitude of the problem. Infect Dis Clin North Am. 1989; 3(2):187-198.
[6] Mader JT, Landon GC, Calhoun J. Antimicrobial treatment of osteomyelitis. Clin Orthop. 1993; 295:87-95.
[7] Ostermann PA, Henry SL, Seligson D. Timing of wound closure in severe compound fractures. Orthopedics. 1994; 17(5):397-399.
[8] Price JS, Tencer AF, Arm DM et al. Controlled release of antibiotics from coated orthopedic implants. J Biomed Mater Res. 1996; 30(3):281-286.
[9] Seligson D, Klemm K. Adult posttraumatic osteomyelitis of the tibial diaphysis of the tibial shaft. Clin Orthop Relat Res. 1999; 360:30-36.
[10] Maurer D J, Merkow R L, Gustilo R B. Infection after intramedullary nailing of severe open tibial fractures initially treated with external fixation. J Bone Joint Surg Am.1989; 71(6):835-838.
[11] Schierholz JM, Beuth J. Implant infections: a haven for opportunistic bacteria. J Hosp Infect. 2001; 49(2): 87-93.
[12] Green SA. Complications of external skeletal fixation. Clin Orthop. 1983; 180 (11): 109-116.
[13] Ahlborg HG, Josefsson PO. Pin-tract complications in external fixation of fractures of the distal radius. Acta Ortho Scand. 1999; 70(2): 116-118.
[14] Garberina MJ, Fitch RD, Hoffmann, ED, et al. Knee arthrodesis with circular external fixation. Clin Ortho Relat Res. 2001; 382: 168-178.
[15] Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med. 2004; 350(14): 1422.
[16] Flock JI, Brennan F. Antibodies that block adherence of to fibronectin [letter]. 1999; 7(4): 140-141.
[17] Schmidmaier G, Wildemann B, Stemberger A, et al. Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res, Applied Biomat. 2001; 58(4): 449-455.
[18] Schmidmaier G, Wildemann B, Bail H, et al. Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-?1) from a biodegradable poly(D,L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone. 2001; 28(4): 341-350.
[19] Hutmacher D, Hurzeler MB, Schliephake H. A review of material properties of 128biodegradable and bioresorbable polymers and devices for GTR and GBR applications. Int J Oral Maxillofac Implants. 1996; 11(5): 667-678.
[20] Kulkarni RK, Moore EG, Hegyeli AF, et al. Biodegradable poly(lactic acid) polymers. J Biomed Mater Res. 1971; 5(3): 169-181.
[21] Kulkarni RK, Pani KC, Neuman C, et al. Polylactic acid for surgical implants. Arch Surg. 1966; 93(5):839-843.
[22] Gollwitzer H,Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. JAC. 2003; 51(3):585-591.
[23] Acar JF, Goldstein GW. Antibiotics in laboratory medecine. 3rd ed. Baltimore, USA: Williams, Wilkins; 1991: 17-52.
[24] Harris LG, Richards RG. Staphylococci and implant surfaces: a review. Injury. 2006; 37(2)(suppl 2): S3-S14.
[25] Checketts R, Otterburn M, MacEachern G. Pin track infection: definition, incidence and prevention. Int J Orthop Trauma. 1993; 3(3):16-18.
[26] Mahan J, Seligson D, Henry SL, et al. Factors in pin tract infections. Orthopedics.1991; 14(3):305-308.
[27] Hargreaves DG, Pajkos A, Deva AK, et al. The role of biofilm formation in percutaneous Kirschner-wire fixation of radial fractures. J Hand Surg Br. 2002; 27(4):365-368.
[28] Worlock P, Slack R, Harvey L, Mawhinney R. The prevention of infection in open fractures: an experimental study of the effect of fracture stability. Injury. 1994; 25(1):31-38.
[29] Bagnoa A, Genovesea M, Luchinia A,et al. Contact prolometry and correspondence analysis to correlate surface properties and cell adhesion in vitro of uncoated and coated Ti and Ti6Al4V disks. Biomaterials. 2004; 25(12): 2437-2445.
[30] Barth E, Myrvik QM, Wagner W, Gristina AG. In vitro and in vivo comparative colonization of Staphylococcus aureus and Staphylococcus epidermidis on orthopaedic implant materials. Biomaterials. 1989; 10(5): 325-328.
[31] Von Eiff C, Proctor RA, Peters G. Coagulase-negative staphylococci. Pathogens have major role in nosocomial infections. Postgrad Med. 2001; 110(4): 63-76.
[32] Richards RG, Harris LG, Schneider E, et al. Antiseptics and antibiotics on implants. Injury. 2006; 37(2)(suppl 1): S113-S116.
[33] Schmidmaier G, Lucke M, Wildemann B,et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury. 2006; 37(suppl 2): S105-112.
[34] Kalicke T,Schierholz J,Schlegel U, et al. Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants: an in vitro and in vivo study. J Orthop Res . 2006; 24(8): 1622.