Bone Substitution and Augmentation in Trauma Surgery with a Resorbable Calcium Phosphate Bone Cement

European Journal of Trauma and Emergency Surgery - Synthetically manufactured bone substitute materials are widely used to fill cancellous bone defects in fracture treatment. By using these...     

Bone Substitution and Augmentation in Trauma Surgery with a Resorbable Calcium Phosphate Bone Cement

Background and Purpose:  

Synthetically manufactured bone substitute materials are widely used to fill cancellous bone defects in fracture treatment. By using these materials, complications occurring with the harvesting of autologous bone such as inflammation, hemorrhage and pain are prevented. Ideally, after osteointegration, the bone substitute resorbs, and complete restoration of bone architecture is achieved. Until now, clinical experience is limited to non-fully resorbable calcium phosphates, e. g., hydroxyapatite. Previous studies have revealed a fully resorbable pure calcium phosphate, which is applied in a paste form as a bone implant and results in complete resorption and biocompatibility. The purpose of this prospective, uncontrolled clinical study was to investigate the safety and performance of this new resorbable bone substitute material.     

Adult Stem Cell Mobilization Enhances Intramembranous Bone Regeneration: A Pilot Study

Background  

Stem cell mobilization, which is defined as the forced egress of stem cells from the bone marrow to the peripheral blood (PB) using chemokine receptor agonists, is an emerging concept for enhancing tissue regeneration. However, the effect of stem cell mobilization by a single injection of the C-X-C chemokine receptor type 4 (CXCR4) antagonist AMD3100 on intramembranous bone regeneration is unclear.     

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

The small GTPase Rho and Rho-associated protein kinase (Rho kinase, ROCK) signal participates in a variety of biological functions including vascular contraction, tumor invasion, and penile erection. Evidence also suggests Rho-ROCK is involved in signaling for mesenchymal cellular differentiation. However, whether it is involved in osteoblastic differentiation is unknown. We therefore asked whether Rho-ROCK signaling participates in recombinant human bone morphogenetic protein (rhBMP-2)-induced osteogenesis both in vitro and in vivo. Continuous delivery of a specific ROCK inhibitor (Y-27632) enhanced ectopic bone formation induced by rhBMP-2 impregnated into an atelocollagen carrier in mice without affecting systemic bone metabolism. Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells. These effects were associated with increased expression of BMP-4 gene. Expression of a dominant negative mutant of ROCK in ST2 cells promoted osteoblastic differentiation, while a constitutively active mutant of ROCK attenuated osteoblastic differentiation and the ROCK inhibitor reversed this phenotype. Thus, ROCK inhibits osteogenesis, and a ROCK inhibitor in combination with the local delivery of rhBMP/collagen composite may be clinically applicable for stimulating bone formation.     

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.     

自固化磷酸钙人工骨体内植入长期实验研究

目的：自固化磷酸钙（CPC）是新型的非陶瓷型羟基磷灰石类人工骨材料。本文观察了CPC植入体内的实验结果。方法：将术中预制成形的CPC植入兔股骨髁处缺损和肌肉内，观察18个月。结果：CPC只引起一过性的炎症反应，与骨直接愈合。12个月时CPC降解约12％，18个月时约为19％，降解处由骨组织替代。CPC与骨为界面结合，CPC的降解为溶解降解，是两个重要发现。结论：CPC适合于非负重或低负重部位骨缺损的修复。     

Vitamin-D Binding Protein Does Not Enhance Healing in Rat Bone Defects: A Pilot Study

Vitamin D-binding protein (DBP) has an anabolic effect on the skeleton and reportedly enhances bone ingrowth. We used an in vivo critical bone defect model to determine whether local administration of DBP promotes bone defect healing. We created a 5-mm segmental bone defect in the radial shaft in a rat model. Forty-eight rats were assigned to eight groups: local application of 1 μg, 5 μg, 10 μg, or 50 μg DBP (DBP-1, DBP-5, DBP-10, DBP-50), autogenous bone marrow mononuclear cells with or without 10 μg DBP (BM-DBP-10, BM), 80 μg BMP-2 delivered in gelatin sponge (BMP-2), and the sham operated group. Radiographic evaluation, histological stains, and epifluorescence microscopy were performed. Grossly, all bone gaps of the BMP-2 group were solidly bridged by callus, while all those in the sham operated group remained unhealed by 9 weeks. Only one specimen of the BM-DBP-10 and DBP-50 groups and three specimens of the BM group were solidly healed; pseudarthroses occurred in all of the other specimens. Histological study and radiographs of the specimens showed similar results. We did not observe the enhanced bone healing reported in a previous study.     

Liposomal Formulation Increases Local Delivery of Amphotericin from Bone Cement: A Pilot Study

Background  

Amphotericin is a highly toxic hydrophobic antifungal. Delivery of amphotericin from antifungal-loaded bone cement (ALBC) is much lower than would be expected for an equivalent load of water-soluble antibacterials. Lipid formulations have been developed to decrease amphotericin toxicity. It is unknown how lipid formulations affect amphotericin release and compressive strength of amphotericin ALBC.     

磷酸钙骨水泥强化骨质疏松绵羊腰椎力学强度的动态观察

目的观察磷酸钙骨水泥（calcium phosphate cement,CPC）强化骨质疏松绵羊腰椎生物力学强度的体内动态变化。方法成年雌性绵羊12只行去势手术后饲养1年,测量去势前后腰椎骨密度。取L2~L5为实验对象,空白组不给予任何处理,CPC组中,经椎弓根向椎体内注射CPC 2.0 mL。于术后1 d、6周、12周和24周四个时间点各随机处死3只绵羊,对椎体行压缩实验,分别测量各组中椎体的最大压缩应力（ultimate compressive stress,σult）和能量吸收值（energy absorption value,EAV）,对比分析同一时间点不同方法之间和同一方法的不同时间点之间的力学指标。结果去势1年后绵羊腰椎骨密度显著下降,差异具有统计学意义（P〈0.05）,骨质疏松绵羊模型建立成功。空白组中各时间点之间的σult和EAV均无显著性差异（P〉0.05）,而CPC组中各时间点之间的σult和EAV也均无显著性差异（P〉0.05）;在同一时间点,CPC组螺钉的σult和EAV均显著高于对照组（P〈0.05）。结论 CPC对骨质疏松椎体的即时强度和远期强度均有显著的强化效果,它对椎体的强化效果在体内是动态稳定的,为脊柱达到坚强骨性融合提供了良好的力学环境。CPC作为一种生物相容性好、可降解吸收、可促骨生成和机械强度好的材料具有广阔临床应用前景。     

Influence of Gender and Fixation Stability on Bone Defect Healing in Middle-aged Rats: A Pilot Study

Background  

Gender and stability of fixation independently influence bone regeneration but their combined effects are unclear.     

Bone Morphogenetic Protein 2 (BMP-2) Enhances BMP-3, BMP-4, and Bone Cell Differentiation Marker Gene Expression During the Induction of Mineralized Bone Matrix Formation in Culturesof Fetal Rat Calvarial Osteoblasts

Normal bone formation is a prolonged process that is carefully regulated and involves sequential expression of growth regulatory factors by osteoblasts as they proliferate and ultimately differentiate. Since this orderly sequence of gene expression by osteoblasts suggests a cascade effect, and BMP-2 is capable of initiating and maintaining this effect, we examined the effects of BMP-2 on expression of other BMPs and compared these effects with the expression pattern of bone cell differentiation marker genes in primary cultures of fetal rat calvarial (FRC) osteoblasts. To examine the gene expression profile during bone cell differentiation and bone formation, we also examined the effects of rBMP-2 on bone formation in vivo and in vitro. rBMP-2 stimulated bone formation on the periosteal surface of mice when 500 ng/day rBMP-2 was injected subcutaneously. When rBMP-2 was added to primary cultures of FRC osteoblasts, it accelerated mineralized nodule formation in a time and concentration-dependent manner (10–40 ng/ml). rBMP-2 (40 ng/ml) enhanced BMP-3 and -4 mRNA expression during the mineralization phase of primary cultures of FRC osteoblasts. Enhancement of BMP-3 and -4 mRNA expression by rBMP-2 was associated with increased expression of bone cell differentiation marker genes, alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), osteopontin (OP), and bone sialoprotein (BSP). These results suggest that BMP-2 enhances expression of other BMP genes during bone cell differentiation. BMP-2 may act in a paracrine fashion in concert with other BMPs it induces to stimulate bone cell differentiation and bone formation during remodeling. Received: 27 November 1995 / Accepted: 19 July 1996     

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     

可注射磷酸钙骨水泥联合骨形态发生蛋白-2治疗老年肱骨近端骨折疗效分析

目的采用回顾性分析方法,观察可注射磷酸钙骨水泥(calcium phosphate cement,CPC)联合重组骨形态发生蛋白(recombinant human bone morphogenetic protein,rh BMP-2)作为植骨材料在老年肱骨近端骨折中的临床疗效和安全性。方法对59例老年肱骨近端骨折手术复位后的骨缺损分别采用可注射rh BMP-2/CPC(实验组)和单纯CPC(对照组)进行充填,并用PHILOS接骨板进行内固定。比较两组患者术后Lane-Sandhu X线评分和肩关节功能的差异。结果全部病例经过平均14.2个月随访。切口局部无搔痒感或疼痛。随访发现实验组术后平均20.8周获得骨性愈合,优于对照组的25.8周。通过Lane-Sandhu评分结果显示:实验组与对照组的X线评分比较差异有统计学意义(P0.05)。而实验组和对照组对比术后关节功能评分提示:运用可注射rh BMP-2/CPC人工骨患者在术后1年的Neer关节功能评分表结果优于单纯运用CPC人工骨患者(P0.05)。结论可注射rh BMP-2/CPC具有安全、方便、副作用小、充填效果确实等优点,能有效避免复位后骨量的再丢失,可促进骨折的愈合过程,是充填老年肱骨近端骨折骨缺损的较佳方法之一。     

微小颗粒骨磷酸钙复合物作为骨组织工程支架材料的实验研究

目的探讨使用同种异体微小颗粒骨磷酸钙骨水泥（CPC）复合物作为骨组织工程支架材料的方法。方法采用同种异体微小颗粒骨CPC复合物作为支架材料，将rh—BMP与CPC液相混合，再与兔骨膜成骨细胞及毛细血管内皮细胞复合培养，制成组织工程化人工骨。将人工骨移植到兔骶棘肌肌袋内，于术后4、8、12周进行Masson三色法组织学观察、扫描及透射电镜观察，观察其骨化及血管化情况。再将兔的桡骨制成骨缺损模型，用组织工程人工骨进行修复，于术后4、8、12周摄X线片检查、苏木精-伊红染色，观察骨缺损修复情况。结果肌袋内成骨实验，除4周时A组与B组的新骨形成面积百分比无显著性差异（P〉0．05）外，其余时间段两组的新生骨面积及新生血管面积相比具有显著性差异（P〈0．05）。修复骨缺损实验，A组新骨形成的速度、质量均明显优于B组。结论同种异体微小颗粒骨CPC复合物是一种良好的骨组织工程支架材料，有利于组织工程骨快速完成骨化及血管化。     

Bone Fracture Healing with Umbilico-Placental Mononuclear Cells: A Controlled Animal Study

Background:   

Fracture healing is a significant process in orthopedics. In this controlled animal study, our aimis to expose the healing effects of cord blood umbilico-placental mononuclear cells (UPMNCs) on bone fractures.     

胸腰椎骨质疏松骨折行CPC灌注成形的力学实验

目的探讨磷酸钙骨水泥(calcium phosphate cement,CPC)注射椎体成形术后对胸腰椎骨质疏松骨折椎体的力学影响。方法建立前屈方向加载单椎体骨折模型,对胸腰椎骨质疏松骨折标本行CPC成形强化,骨折前、成形后分别行屈曲压缩力学实验。结果椎体内注射CPC能明显恢复骨质疏松骨折椎体的力学性质。骨质疏松性胸腰椎标本行CPC灌注成形可以恢复椎体的强度和刚度,分别增加16.92%(P<0.05)和22.31%(P<0.05)。结论椎体内注射CPC能明显恢复骨质疏松骨折椎体的力学性质。     

磷酸钙骨水泥强化椎弓根螺钉对骨质疏松性椎体骨折的临床意义

目的 :评价磷酸钙骨水泥 (calciumphosphatecement ,CPC)强化和修复椎弓根螺钉的生物力学效果。方法 :6具新鲜老人骨质疏松的脊柱标本 ,从T11～L4 共 36个椎体 ,随机选取其中 32个 ,分为 4组 ,每组 8个。A组 :随机选择一侧椎弓根放置直径为 6 .5mm的椎弓根螺钉 ,另一侧以直径为 3.5mm的钻头导孔。向两侧椎弓根孔道注入配制好的磷酸钙骨水泥 (CPC) 3～ 5ml ,体温下 ( 37℃ )放置 2 4h后 ,再行前述拔出实验。B组 :应用PMMA进行修复和强化 ,作为对照 ,操作方法同A组。C组 :植入椎弓根螺钉 ,添加或不添加CPC ,进行周期抗屈实验。D组 :相同方法 ,应用PMMA作为对照。结果 :CPC骨水泥强化组和修复组拔出力明显高于对照组 ,差异有显著性意义 (P <0 .0 5)。结论 :在植入椎弓根螺钉时添加具有生物活性的磷酸钙 (CPC)骨水泥可显著提高其初始稳定性     

Bone Vascularization and Bone Healing in the Amputation Stump: An Experimental Study

The osseous healing process of the amputation stump was investigated in adult rabbits. Histological investigation showed that the medullary cavity was closed after 2-3 weeks, chiefly by endosteal callus. After closure of the cavity there was a gradual spongious change in the bone tip and simultaneously the cortex atrophied and the medullary cavity dilated. After amputation on the crus bone rebuilding dominated, whereas after amputation on the femur deterioration of bone was most noticeable. A combination of amputation and medullary plugging caused a change in the course of healing. The medullary cavity did not close until 7-10 weeks after operation and there was distinct periostea] callus formation.

The microangiographic investigation showed a transient hyper-vascularization in the cortex 3-4 weeks after amputation; whereas after simultaneous plugging of the medullary cavity the hypervasculari-zation continued for up to 7 weeks after operation. Following amputation proximally on the crus the arterial supply of the cortex came mainly from the periost, whereas the cortex after distal amputation was vascularized from the medullary cavity. This finding can be due to an interruption of the arterial supply from the nutrient artery associated with proximal amputation, whereas this artery remains intact with amputation distally on the crus.