磷酸钙与聚甲基丙烯酸甲酯制备复合型骨水泥的生物安全性研究

目的探讨磷酸钙(CPC)和聚甲基丙烯酸甲酯(PMMA)按不同比例混合而制备复合型骨水泥(CPC/PMMA)的方法及评价其生物安全性。方法制备CPC/PMMA复合型骨水泥试件并分组,共分为CPC(100%)组、CPC/PMMA(75%、67%、50%、33%、16.7%、9.1%、6.25%、4.8%)组、PMMA(100%)组;通过急性毒性实验、全身亚急性毒性实验、热源实验、致敏实验、溶血实验检测CPC/PMMA复合型骨水泥的生物安全性。结果 CPC(100%)组、CPC/PMMA(75%)组、CPC/PMMA(67%)组、CPC/PMMA(50%)组OD值两两比较差异无统计学意义(P0.05),细胞毒分级为1级,无细胞毒性。CPC/PMMA(50%)组与对照组、CPC(100%)组、PMMA(100%)组小鼠的血常规检、生化检查、脏器湿重、体重变化差异无统计学意义(P0.05)。实验组的组织病理学检查、热源实验、致敏实验、溶血实验未出现异常。结论复合型骨水泥CPC/PMMA制备过程简便可靠,具有良好的生物安全性、血液与组织相容性,无毒性及致敏性。     

复合磷酸钙骨水泥的研究进展

磷酸钙骨水泥(Calcium phosphate cement，CPC)，或羟基磷灰石骨水泥(Hydroxyapatite cement，HAC)，是一种非陶瓷型羟基磷灰石类(HAP)人工骨替代材料，具有良好的生物相容性、可降解性和骨传导能力。由于其克服了陶瓷型HAP修整困难、不易降解等缺点，具有可自固化、随意塑形、使用方便等优点。所以，自1985年研制出来后，已广泛应用于骨科、整形外科、牙科等领域，是比较好的骨替代材料。     

磷酸钙骨水泥的研究进展综述

磷酸钙骨水泥的研究进展综述林立波曾维权骨缺损的修复重建是骨科的一个重要课题。虽然新鲜自体骨是修复重建的一种有效材料，但因供骨来源有限，且增加手术创伤，使其临床应用受到很大限制。寻求合适的骨替代材料用于骨缺损的生物性重建是其出路所在。近几十年来，着...     

磷酸钙骨水泥在骨折治疗中的应用研究与进展

磷酸钙骨水泥（calcium phosphate cement，CPC）又称羟基磷灰石骨水泥（hydroxyaptite cement，HAC）是Brown和Chow于1985年研制成功的一种新型自固化非陶瓷型羟基磷灰石人工骨材料，它克服了钙磷陶瓷脆性大、塑型困难、不能降解等缺点，具有良好的生物相容性、生物活性、可降解性和骨传导能力，且具有随意塑型、使用方便、固化不产热等优点，已广泛应用于骨科、口腔科和整形外科等领域，是近年来国内外研究的热点。本文就CPC在骨科特别是在骨折治疗中的应用研究与进展作一综述。     

磷酸钙骨水泥的研究进展

磷酸钙骨水泥(CPC或CPBC)是一种自固型非陶瓷型羟基磷灰石类材料,1985年由Brown和Chow首先研制出用于骨移植和修复。它是一类以各种磷酸盐为主要成份,在生理条件下具有自固化能力及降解活性、成骨活性的无机材料。它还具有高度的生物相容性,可任意塑型,固化过程等温性等特点,是目前唯一既能自行固化又能产生骨传导效果的骨修复材料。     

脱钙骨基质/磷酸钙复合骨水泥骨诱导活性观察

目的：观察磷酸钙骨水泥（CPC）中加入脱钙骨基质（DBM）后形成的复合骨水泥的成骨诱导活性。方法：将DBM/CPC复合骨水泥分别植入兔背肌肌袋内，于不同时间取材，通过组织学切片、ALP等手段观察异位诱导成骨情况。结果：术后2周，DBM/CPC复合骨水泥组可见间充质细胞增殖、聚集并包绕DBM骨粒。4周时，DBM已有部分吸收，并软骨样细胞和软骨样组织包裹。8周，DBM进一步吸收，软骨细胞和软骨组织逐渐成熟，新骨形成。12周，DBM吸收并被新骨组织部分或大部分代替且相互连接成片。ALP测定结果与组织学观察的新骨形成情况基本一致。结论：DBM/CPC复合骨水泥有较强的异位诱导成骨能力，诱导新骨的形成伴随着材料的降解，可以有效弥补单纯使用CPC时降解速度太慢和无骨诱导能力的不足。     

复合型磷酸钙骨水泥研究进展

磷酸钙骨水泥(CPC)是一种自固化型羟基磷灰石类人工骨替代材料,具有良好的生物相容性和骨传导能力,已成为组织工程支架的一个重要分支.复合型CPC研究还处于初级阶段,添加剂对CPC的性能会有影响,并能不同程度地克服其缺点;对CPC进行成分改性可拓展其应用领域.该文对复合型CPC及其添加剂在骨水泥中的行为、作用疗效、原理的最新研究结果作一综述.     

磷酸钙骨水泥复合微小颗粒骨的体外实验研究

[目的]进行磷酸钙骨水泥复合微小颗粒骨的实验,探讨磷酸钙骨水泥(calcium phosphate cement,CPC)和微小颗粒骨最佳混合比例。[方法]取大耳白兔双侧股骨制作颗粒骨,实验组为颗粒骨和CPC分别以1∶1、1∶2、1∶3、1∶4、1∶5混合固化的材料;对照组为CPC固化的材料。测定两组的固化时间及最大抗压强度;间充质干细胞培养于材料浸提液中,MTT检测细胞增殖;间充质干细胞与各材料共培养5 d后,电镜观察材料表面的细胞量及形态。[结果]MTT检测:比例为1∶2和1∶3组明显促进细胞的增殖,优于其他组,有统计学意义(P0.05)。电镜扫描:1∶2、1∶3组材料表面的细胞生长良好,其他组材料表面的细胞量明显少于这两组。1∶3组材料的固化时间及最大抗压强度适中,与CPC组比较,有统计学意义(P0.05)。[结论]1∶3在可操作性、生物力学、细胞相容性方面是最合适的混合比例。     

磷酸钙骨水泥复合微小颗粒骨修复兔桡骨缺损

[目的]证实磷酸钙骨水泥复合少量自体颗粒骨修复骨缺损的效果,为临床使用提供依据。[方法]手术造成日本大耳白兔双侧桡骨中段15 mm缺损,一侧植入磷酸钙骨水泥与自体颗粒骨以3∶1复合的材料,做为实验组;另一侧植入单纯的磷酸钙骨水泥,做为对照组。在不同的时间点行X线、骨密度、最大扭矩检测,分析实验组及对照组的成骨性能和材料降解程度。[结果]X线检查发现:实验组材料明显促进成骨,8周时材料周围有明显的骨痂,16周时缺损完全修复、材料完全降解,优于对照组;8、16周时,实验组单位面积的骨矿盐含量均高于对照组,统计学检测,P0.01;16周时实验组和对照组的最大扭矩分别为:(0.843±0.016)mN、(0.540±0.029)mN,统计学检验P0.01。[结论]磷酸钙骨水泥与自体颗粒骨以3∶1复合后明显促进了缺损修复和材料降解。     

新型可注射可降解磷酸钙骨水泥对成骨作用影响的实验研究

目的比较单纯的、添加锌锶等元素及复合rhBMP-2的新型可注射可降解磷酸钙骨水泥(CPC)植入机体后的降解及成骨作用,检验材料及其改进剂型在临床应用的可能性。方法将24只雄性新西兰白兔随机分为A,B,C三组,分别为9、9和6只,制备双侧胫骨结节骨缺损模型；于骨缺损处分别置入：A组为单纯新型可注射可降解CPC材料,B组为含锌锶等微量元素的该CPC材料,C组为该CPC材料与rhBMP-2的复合物。观察其全身及植入局部反应,术后4、8、16周取材CT扫描、肉眼及光学显微镜观察材料植入后的局部反应情况并对比观察该三种材料的降解及骨生长情况。组织切片摄像后,每组每时间点各取5幅相片用软件进行图文处理,求得术后骨组织切片中骨组织含量百分比。结果CT扫描、肉眼及光学显微镜观察发现单纯的和含锌锶等微量元素的CPC材料可引导新骨形成,但新骨形成少且慢,与材料降解不同步；复合rhBMP-2的CPC材料组新生骨形成多而早,基本与材料降解同步。术后骨组织含量百分比测定,A组为(41．7±16．6)%,B组为(31．2±12．2)%,C组为(71．7±21．0)%,复合BMP的CPC材料组术后骨组织切片中骨组织含量显著高于另外两组(P＜0．01)。结论复合rhBMP-2的可注射可降解CPC材料可较早地诱导新生骨生成,与单纯的及含锌锶等微量元素的可注射可降解CPC材料相比,更适合于临床使用。     

聚磷酸钙纤维/磷酸钙骨水泥/微小颗粒骨修复骨缺损的实验研究

目的探讨聚磷酸钙纤维(calcium polyphosphate fibers,CPPF)、磷酸钙骨水泥(calcium phosphate cement,CPC)、自体微小颗粒骨复合材料修复骨缺损的能力。方法选用新西兰大白兔72只,双侧桡骨制成1.5cm骨缺损模型,随机分成6组分别植入。A组:CPPF/CPC/微小颗粒骨复合材料;B组:CPC/微小颗粒骨复合材料;C组:单纯微小颗粒骨;D组:CPPF/CPC复合材料;E组:单纯CPC;F组:空白对照组,不植入任何物质。在2、4、8、12周各时相点,分别进行大体观察、X线照片、组织学切片、扫描电镜观察及力学测试。结果A组在12周可使骨缺损修复,在骨缺损修复各时期,其成骨速度及成骨量均好于其他各组。结论CPPF/CPC/微小颗粒骨复合材料有良好的成骨能力、力学特性和生物相容性,有望成为骨组织工程中修复骨缺损的理想材料。     

可吸收骨水泥对椎弓根螺钉稳定性的生物力学影响

目的：验证椎弓根螺钉植入时添加可吸收骨水泥α-BSM^TM对螺钉初始稳定性的影响。方法：采用6具人体新鲜腰椎标本,共16个椎体（L3－L5）,将椎弓根螺钉分别置入两侧椎弓根,随机在一侧加α-BSM^TM,测试螺钉最大轴向拔出力（F－max）和螺钉拔出过程中达到最大轴向拔出力时的能量吸收（E－F－max）及螺钉拔出一个螺距（2．0mm)旦的能量吸收（E－2mm)。结果：同未加α－BSM^TM组相比较,椎弓根螺钉最大轴向拔出力F－max在加入α-BSM^TM后,由370N提高到665N,增加了80％。E－F－max和E－2mm也分别增加了83％和68％,差别有统计学显著意义（Wilcoxon's检验,P＜0．01）。最大轴向拔出力F－max（加和不加α-BSM^TM)与椎体松质骨的骨密度（BMD）紧密相关（r=0.9585,0.9056,P＜0．05）。结论：在椎弓根螺钉植入时添加α-BSM^TM能显著提高其初始稳定性。     

注射式磷酸钙骨水泥在胫骨平台骨折中的应用

目的采用回顾性分析方法,对注射式β-磷酸三钙骨水泥作为植骨材料在胫骨平台骨折中的临床疗效进行评估。方法对23例胫骨平台骨折复位后骨缺损区采用可注射式磷酸钙骨水泥进行填充。结果全部病例平均随访15.4个月,均获得骨性愈合,无骨不连和感染情况发生,内固定无松动及脱落现象。注射式β-磷酸三钙骨水泥术后10～12周开始出现吸收,20～24周大部分吸收,28～32周基本全部吸收。术后6个月和1年膝关节功能良好。结论注射式β-磷酸三钙骨水泥具有安全、方便、副作用小、填充效果确实等优点。固化后具有较强的支撑作用,可提高患者膝关节早期功能锻炼的安全性,促进了骨折的愈合过程,是治疗和填充胫骨骨折骨缺损区的较佳方法之一。     

The Use of Fibrin Glue in the Treatment of Fistula-In-Ano: A Prospective Study

Purpose This prospective study was done to analyze the efficacy of commercial fibrin glue application in the healing of patients with fistulas-in-ano. Methods This clinical trial of 36 patients was performed during the period from November 2003 to May 2004. Thirty men and six women were treated for a fistula-in-ano with commercial fibrin glue application. None of the patients had undergone prior attempts to correct fistulas-in-ano surgically. All patients received preoperative mechanical bowel preparation and prophylactic intravenous antibiotics. In the operating room, the patients underwent an anorectal examination under spinal anesthesia. The external and internal fistula tract openings were then identified. The fistula tract was curetted. Fibrin glue was injected into the external fistula opening until fibrin glue could be seen coming from the internal opening. No dressing was applied over the external opening. Thereafter, the patient was discharged. A 1-week course of oral antibiotics was prescribed. The patients were followed up for 70 weeks with a mean of 54 weeks (range 40–70 weeks). Results The cause of the fistula-in-ano was cryptoglandular in all patients. The overall initial success rate was 77.8% (28/36). No complications were encountered related to the application. Two patients underwent a reapplication with fibrin glue and the fistulas of these patients were all closed. The overall success rate was 83.3% (30/36). Conclusion Fibrin glue application was thus found to be an easy, safe, effective, and useful alternative treatment in the management of fistulas-in-ano. However, our findings need substantiation by increasing the number of patients and prolonging the follow-up duration, as well as carrying out comparative studies.     

脱钙骨基质/磷酸钙复合骨水泥骨诱导活性观察

目的:观察磷酸钙骨水泥(CPC)中加入脱钙骨基质(DBM)后形成的复合骨水泥的成骨诱导活性。方法:将DBM/CPC复合骨水泥分别植入兔背肌肌袋内,于不同时间取材,通过组织学切片、ALP等手段观察异位诱导成骨情况。结果:术后2周,DBM/CPC复合骨水泥组可见间充质细胞增殖、聚集并包绕DBM骨粒。4周时,DBM已有部分吸收,并软骨样细胞和软骨样组织包裹。8周,DBM进一步吸收,软骨细胞和软骨组织逐渐成熟,新骨形成。12周,DBM吸收并被新骨组织部分或大部分代替且相互连接成片。ALP测定结果与组织学观察的新骨形成情况基本一致。结论:DBM/CPC复合骨水泥有较强的异位诱导成骨能力,诱导新骨的形成伴随着材料的降解,可以有效弥补单纯使用CPC时降解速度太慢和无骨诱导能力的不足。     

Effects of Pore Size on the Osteoconductivity and Mechanical Properties of Calcium Phosphate Cement in a Rabbit Model

Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200–300 µm, Group B: 300–450 µm, Group C: 450–600 µm, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo.     

纤维蛋白凝胶复合骨形态发生蛋白和庆大霉素缓释药物治疗感染性骨缺损的实验研究

目的 探讨将纤维蛋白凝胶(FG)作为骨形态发生蛋白(BMP)及庆大霉素的共同载体,一期治疗感染性骨缺损。方法 48只青紫兰兔,制作慢性骨髓炎模型,清创后造成胫骨干骺端内侧1.5 cm长半环形骨缺损,采用三种方法进行处理:A组,植入FG、BMP和庆大霉素复合物;B组植入FG/BMP复合物;C组作为空白对照。术后观察动物一般情况,作骨细菌培养及其计数,X线摄片及组织学检查。结果 A组感染控制及骨修复均良好,感染控制率、再生骨量明显优于B组;B、C两组在感染控制率上无显著差异;C组动物骨修复差。结论 FG、BMP及庆大霉素复合物具有抗感染及促进成骨的双重作用,可用于感染性骨缺损的治疗,也可用于污染严重的开放性损伤造成的骨缺损的治疗,方法简便、易行。     

The Wound-Healing Effect of Fibrin Glue for Tracheal Anastomosis in Experimental Pulmonary Surgery

The leakage of tracheal anastomoses is one of the major complications that occurs after tracheal reconstruction. Improved reinforcing methods for anastomoses would thus be clinically useful. To find a better technique, we examined the postoperative would-healing effect of fibrin glue on tracheal anastomosis in the rat. Experimental rats were divided into two groups. In the control group (n = 21), the trachea was anastomosed by interrupted absorbable sutures. In the fibrin glue group (n = 21), the trachea was anastomosed in the same manner as the control group, with the addition of fibrin glue around the area of anastomosis. In the two groups, we studied the amount of hydroxyproline and histological findings on the seventh, 14th, and 21st postoperative day. The amount of hydroxyproline and collagen fibers in the fibrin glue group was more than in the control group on the seventh postoperative day. These results suggest that fibrin glue has a promotive effect in the healing of tracheal anastomosis. Received: August 24, 2000 / Accepted: May 15, 2001     

Defect Reconstruction in Articular Calcaneus Fractures with a Novel Calcium Phosphate Cement

Background: Major osseous defects in trauma or tumor patients require surgical reconstruction. While transplantation of autogenous or allogenous bone is still regarded as the standard, a multitude of alternative substitute materials has been developed in the recent years. Currently, the majority of commercially available products is based on calcium phospate minerals which are known to be osteoconductive, but in which resorption occurs slowly, if at all. A new class of calcium phosphate cements has recently been introduced that may offer better resorbability due to their nanocrystalline structure. Patients and Methods: In a prospective study of eleven patients with twelve joint depression calcaneal fractures requiring open reduction and internal stabilization, the subchondral defects were filled with a novel nanocrystalline calcium phosphate cement (Biobon^?). Nine patients with ten fractures underwent a 1-year clinical and radiologic follow-up. Results: The postoperative course was uneventful except for one postoperative infection. On follow-up X-rays, the contours of the cement material became blurred and its size decreased. Biopsies taken after 6–8 months during plate removal demonstrated residual cement with intense osseointegration. Signs of inflammatory tissue response were absent, and part of the material had been replaced by new bone. Conclusions: The substitute material investigated in this study has a high biocompatibility and may represent an interesting alternative to bone grafts. Compared to sintered calcium phosphates, the resorbability of the new cement appears superior due to its nanocrystalline structure. The low compressive strength, however, does not permit early weight bearing and requires additional stabilization with osteosynthetic implants. Received: October 12, 2001; revision accepted: November 8, 2002 Correspondence Address Michael R. Sarkar, MD, Department of Trauma, Hand and Reconstructive Surgery, University of Ulm, 89070 Ulm, Germany, Phone /+49/731) 500-1, Fax -27349, e-mail: michael.sarkar@medizin.uni-ulm.de     

Evaluation of Antibiotic-loaded Calcium Phosphate Bone Cement in a Cranium-infected Experimental Model

Treatment of calvarial defects has remained a challenge in reconstruction surgery, especially because of infection at these sites. We produced a bactericidal biomaterial for treating infected bone defects by using calcium phosphate bone cement mixed with antibiotics. We evaluated the usefulness of this material mixed with the antibiotic vancomycin in a cranium-infected rat model. The concentration of vancomycin used was 5.0 wt%, as reported in our previous study. In order to establish the rat model, a cranium defect (diameter, 5 mm) was made that was infected with methicillin-resistant Staphylococcus aureus (MRSA). Thirty-six rats were divided into 6 groups depending on whether an autologous graft or bone cement with or without antibiotic was used for the defect. After 1 and 4 weeks, abscess formation was checked, tissue bacterial counts were determined, and pathological examination was performed. At both 1 and 4 weeks, no MRSA was detected on tissue bacterial culture or pathological examination in groups that received bone cement with antibiotics. In groups that received bone cement without antibiotic, MRSA was detected, and the bone cement had compromised and disintegrated into several slices. In conclusion, bone cement that contains antibiotics appears to be effective not only for reconstruction in cases of cranial defect, but also in terms of preventing infection.