A biomechanical and histological evaluation of a bioresorbable lumbar interbody fusion cage

Novel spinal interbody fusion cages made of bioactive and bioresorbable composites by a unique forging process were developed. Previous in vitro study demonstrated that these cages marked excellent biomechanical values. The purpose of the present in vivo study was to evaluate the viability and advantage of this forged composite of uncalcined hydroxyapatite/poly L-Lactide (F-u-HA/PLLA) cage radiographically, biomechanically, and histologically, when compared to conventional autologous iliac bone (AIB) and carbon fiber cage (CFC). Twenty-five mature sheep underwent posterior lumbar interbody fusion at L2-3 level with pedicle screws system made of titanium. Three types of interbody fusion implants were grafted: AIB (n = 7), CFCs (n = 9), F-u-HA/PLLA cages (n = 9). Two types of cages were packed with autologous fragmented cancellous bone harvested locally. All animals were euthanized at 120 days after surgery. The fusion scoring using the coronal view CT scans was designed to three-dimensionally evaluate fusion quality within and around cages. The mean CT scores of three groups were 33.3 points, 35.0 points, and 33.6 points in AIB, CFC, and F-u-HA/PLLA cage groups, respectively (full-score: 56 points). Statistical differences were not detected among the three groups. The mean range of motion values among fused groups had no significant difference under all pure loadings. The range of motion showed strong and significant correlation with the CT fusion scores. Histologic results demonstrated that F-u-HA/PLLA cages contacted with the surrounding bone directly, and CFC was encircled with thick fibrous tissue layers without any sign of inflammation around cages. The fusion quality of fused spinal segment using F-u-HA/PLLA cages was equal to that of AIB or CFCs both radiographically and biomechanically. In the histological observation, biocompatibility of F-u-HA/PLLA cage was obviously superior to CFC. It has been confirmed that the novel bioactive and bioresorbable cages had valuable advantages over existing CFC for use in spinal reconstructive surgery.     

A polycaprolactone-tricalcium phosphate composite scaffold as an autograft-free spinal fusion cage in a sheep model

Titanium (Ti) based spinal fusion cages are frequently used in the clinics for the treatment of spinal degeneration and related diseases, however, their further clinical application is generally harassed by several drawbacks such as stress shielding, non-biodegradability and additional bone grafting procedure. Our earlier work has demonstrated the efficacy of a biodegradable macro-porous polycaprolactone-tricalcium phosphate (PCL-TCP) composite scaffold in promoting bony tissue ingrowth as well as its ability to sustain mechanical loads upon implantation into an orthotopic defect site. In this study, we investigated the use of PCL-TCP scaffold as an autograft-free spinal fusion cage in a preclinical sheep model over 12 months, and compared the fusion efficacy against Ti cages incorporated with autografts. Results showed that despite PCL-TCP scaffold as an autograft-free cage attaining a slower fusion rate at early stage (6 month), it achieved similar degree of spinal fusion efficacy as Ti cages aided with autograft at 12 month post-operation as evidenced by the radiographic and histological evaluation. PCL-TCP cages alone demonstrated better bone ingrowth with 2.6 fold higher bone/interspace ratio (B/I) and more homogeneous bone tissue distribution compared with that of the Ti cages (88.10  ±  3.63% vs. 33.74  ±  2.78%, p < 0.05) as seen from the histological and micro-CT analysis. Moreover, besides the bone tissue ingrowth, a quantitative approach was illustrated to accurately evaluate the osteointegration of fusion cage with surrounding bone tissue, and showed a 1.36 fold higher degree of osteointegration occurred in PCL-TCP cage group than Ti cage group (CS/PC: 79.31  ±  3.15% vs 58.44  ±  2.43%, p < 0.05). Furthermore, biomechanical analysis showed comparable mechanical strength of fused segments in both groups in terms of the range of motion and stiffness at 12 month (p > 0.05). The degradation profile of the PCL-TCP cages was noted to increase in tandem with new bone ingrowth into the pores, while maintaining good structural integrity necessary for supporting the spinal interbody segments. Therefore, with the better osteointegration, more bone tissue ingrowth as well as its favorable biodegradable and radiolucent properties, PCL-TCP cage has been demonstrated to be a promising candidate as an autograft-free fusion cage for clinical application.     

In vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages

The in vitro and in vivo degradation of poly-L-lactic acid cages used as an adjunct to spinal arthrodesis was investigated. In the in vitro experiments cages were subjected to aging up to 73 weeks in phosphate-buffered solution (pH 7.4) at 37 degrees C. Inherent viscosity, crystallinity, and mechanical strength were determined at different time points. In the in vivo study, the poly-L-lactic acid cages were packed with bone graft and implanted in the L3-L4 spinal motion segment of 18 Dutch milk goats. At 12, 26, and 52 weeks, the motion segments were isolated and poly-L-lactic acid samples retrieved. On evaluation, the in vivo implanted cages showed an advanced decline in inherent viscosity compared to the cages subjected to in vitro degradation experiments. At 6 months of implantation, the geometrical shape and original height of 10 mm was maintained during 6 months of follow up. This finding fits well with the observation that mechanical strength was maintained for a period of 6 months in vitro. At 12 months, the poly-L-lactic acid cage had been disintegrated into multiple fragments with signs of absorption. Despite the high-load-bearing conditions, the poly-L-lactic acid cage allowed interbody fusion to occur without collapse of the cage.     

颈椎解剖与钛质网笼生物力学研究进展

钛质网笼作为颈前路椎体次全切除减压融合术（anterior cervical corpectomy and fusion,ACCF）中使用的融合器之一,不仅能够在术中即刻重建颈椎稳定性、维持椎间高度及生理曲度,而且可以避免自体取骨造成供骨区并发症的问题,故成为ACCF术中较为常用的内植物。但传统钛笼多存在应力遮挡、钛笼下沉等问题,在一定程度上影响了手术效果,甚至导致严重术后并发症,需要行翻修手术。目前已有多种新型钛笼问世,一定程度上解决了传统钛笼带来的问题。生物力学评价及其测试方法是评判一款新型脊柱融合器能否应用于临床必不可少的过程。综述颈椎解剖相关生物力学、传统钛笼与新型钛笼生物力学特性的相关研究,为传统钛笼的改进以及新型钛笼的研发提供新思路。     

Micro-observation and characterization of bonding between bone and HA-glass-titanium functionally gradient composite

Bioactive composite implants consisting of hydroxyapatite (HA)-glass (G) ceramic layer and Ti-6AI-4V alloy, so-called HA-G-Ti functionally gradient implant, were provided for investigating the bonding behaviour of bone to the implant in vivo. The HA-G-Ti composites were implanted in femur and tibia of dog for various periods (1-12 month). Microstructural appearance of the interface between bone and the HA-G coating layer as well as the transverse sections of the HA-G coating layer and further apposition of bone to the implant have been studied in detail with SEM. The ingress of collagen fibres into the HA-G coating layer and the deposit of apatite on the collagen fibres and HA crystal grains being containing within the HA-G coating layer have been observed. Radiographical experiments indicate that the reparative process in the bone tissue surrounding the implants is markedly ahead even at one month after implantation. FT-IR measurement and X-ray diffraction were carried out for studying the characterization of the calcified bone matrix around the implants and the new bone proliferated along the HA-G-coated face (surface).     

颈椎同种异体骨笼椎间融合的组织学研究

目的：研究颈椎同种异体骨笼在颈椎融合过程中的组织学变化和融合效果。方法：采用12只绵羊行C3,4 C4,5椎间盘摘除后，分别植入自体髂骨与同种异体骨笼，于术后4、12、24周分别处死动物，行大体标本观察、光镜观察和扫描电镜观察。结果：同种骨笼植入后4周骨笼轮廓完整，周边出现吸收腔，腔壁表面有薄层新骨形成。12周，笼壁与椎体之间界线消失，大部分的骨陷窝中有骨细胞，新骨与死骨交织．成骨活动仍在进行，爬行替代尚未结束。24周时，上、下椎体完全骨性连接，骨笼被新骨代替，完成骨性融合。结论：同种异体骨笼充填自体松质骨植入颈椎间后能获得满意的脊柱融合效果，并可以逐步被新骨取代，是一种理想的椎间植人物。     

矿化胶原型椎间融合器在山羊颈椎椎间融合中的初步效果观察

目的 初步评价矿化胶原型椎间融合器对活体羊颈椎的融合效果.方法 选取12只2年龄山羊,经颈椎前路分别在每只羊C2/3和C3/4节段植入矿化胶原(MC)型椎间融合器(实验组)及聚醚醚酮(PEEK)型椎间融合器(对照组),两组融合器内均填塞自体骨,并常规使用颈椎前路钛板和螺钉系统固定.术后3个月随机处死6只羊,取颈椎标本行...     

Experimental and clinical performance of porous tantalum in orthopedic surgery

Porous tantalum, a new low modulus metal with a characteristic appearance similar to cancellous bone, is currently available for use in several orthopedic applications (hip and knee arthroplasty, spine surgery, and bone graft substitute). The open-cell structure of repeating dodecahedrons is produced via carbon vapor deposition/infiltration of commercially pure tantalum onto a vitreous carbon scaffolding. This transition metal maintains several interesting biomaterial properties, including: a high volumetric porosity (70-80%), low modulus of elasticity (3MPa), and high frictional characteristics. Tantalum has excellent biocompatibility and is safe to use in vivo as evidenced by its historical and current use in pacemaker electrodes, cranioplasty plates and as radiopaque markers. The bioactivity and biocompatibility of porous tantalum stems from its ability to form a self-passivating surface oxide layer. This surface layer leads to the formation of a bone-like apatite coating in vivo and affords excellent bone and fibrous in-growth properties allowing for rapid and substantial bone and soft tissue attachment. Tantalum-chondrocyte composites have yielded successful early results in vitro and may afford an option for joint resurfacing in the future. The development of porous tantalum is in its early stages of evolution and the following represents a review of its biomaterial properties and applications in orthopedic surgery.     

Surface engineering of stainless steel materials by covalent collagen immobilization to improve implant biocompatibility

It was shown recently that the deposition of thin films of tantalum and tantalum oxide enhanced the long-term biocompatibility of stainless steel biomaterials due to an increase in their corrosion resistance. In this study, we used this tantalum oxide coating as a basis for covalent immobilization of a collagen layer, which should result in a further improvement of implant tissue integration. Because of the high degradation rate of natural collagen in vivo, covalent immobilization as well as carbodiimide induced cross-linking of the protein was performed. It was found that the combination of the silane-coupling agent aminopropyl triethoxysilane and the linker molecule N,N'-disulphosuccinimidyl suberate was a very effective system for collagen immobilizing. Mechanical and enzymatic stability testing revealed a higher stability of covalent bound collagen layers compared to physically adsorbed collagen layers. The biological response induced by the surface modifications was evaluated by in vitro cell culture with human mesenchymal stem cells as well as by in vivo subcutaneous implantation into nude mice. The presence of collagen clearly improved the cytocompatibility of the stainless steel implants which, nevertheless, significantly depended on the cross-linking degree of the collagen layer.     

Biomimetic coating of compound titania and hydroxyapatite on titanium

The modification on the titanium implant surface is an effective method to improve the biocompatibility of titanium. This article describes efforts to improve implant biocompatibility by applying titania and hydroxyapatite to form a three-layer coating on the titanium surface. This three-layer coating is made up of HA as the top layer (formed by hydrothermal treatment), porous TiO2 as the middle layer (formed by micro-arc oxidation) and a dense TiO2 film as the inner layer (formed by preanodic oxidation). The physicochemical characteristics, cell behavior and in vivo studies were assessed. The physicochemical characteristics were investigated using scanning electron micoscopy observation, fibronectin and laminin adsorption, corrosion test and X-ray diffraction analysis. Cell behavior included morphology observation with scanning electron microscopy (SEM), number count with methylthiazol tetrazolium (MTT) assay and Alkaline phosphatase (ALP, a representative enzyme of osteoblastic differentiation) activity of osteoblast-like MC3T3-E1 cells. In study in vivo the specimens were embedded in skull wound for repair. By the analysis of experiments, the titanium coated with this three-layer coating has been proved to have excellent corrosion resistance and good biocompatibility, which can promote cell proliferation and bone formation. So this modified titanium is an improved alternative to untreated titanium for bone repair applications.     

Structural and mechanical evaluations of a topology optimized titanium interbody fusion cage fabricated by selective laser melting process

A topology optimized lumbar interbody fusion cage was made of Ti-Al6-V4 alloy by the rapid prototyping process of selective laser melting (SLM) to reproduce designed microstructure features. Radiographic characterizations and the mechanical properties were investigated to determine how the structural characteristics of the fabricated cage were reproduced from design characteristics using micro-computed tomography scanning. The mechanical modulus of the designed cage was also measured to compare with tantalum, a widely used porous metal. The designed microstructures can be clearly seen in the micrographs of the micro-CT and scanning electron microscopy examinations, showing the SLM process can reproduce intricate microscopic features from the original designs. No imaging artifacts from micro-CT were found. The average compressive modulus of the tested caged was 2.97+/-0.90 GPa, which is comparable with the reported porous tantalum modulus of 3 GPa and falls between that of cortical bone (15 GPa) and trabecular bone (0.1-0.5 GPa). The new porous Ti-6Al-4V optimal-structure cage fabricated by SLM process gave consistent mechanical properties without artifactual distortion in the imaging modalities and thus it can be a promising alternative as a porous implant for spine fusion.     

Carbon fiber-reinforced carbon as a potential implant material

A carbon fiber-reinforced carbon is being evaluated as a promising implant material. In a unidirectional composite, high strengths (1200 MN/m2 longitudinal flexural strength) and high modulus (140 GN/m2 flexural modulus) may be obtained with an interlaminar shear strength of 18 MN/m2. Alternatively, layers of fibers may be laid in two directions to give more isotopic properties. The compatibility of the material with bone has been studied by implanting specimens in holes drilled in rat femora. For a period of up to 8 weeks, a thin layer of fibrous tissue bridged the gap between bone and implant; but this tissue mineralizes and by 10 weeks, bone can be observed adjacent to the implant, giving firm fixation. Potential applications include endosseous dental implants where a greater strength in the neck than that provided by unreinforced carbon would be advantageous.     

面向个性化椎间融合器生物力学评价的有限元建模因素影响分析

目的有限元分析已广泛应用于个性化椎间融合器生物力学的评价和优化。针对有限元建模过程中存在的耗时长、计算要求高、参数选择依赖主观经验的问题,本文研究有限元建模因素对仿真结果的影响,为提高个性化椎间融合器生物力学评价中有限元建模效率提供科学依据。方法以L3、L4节段腰椎融合器设计与优化为例,选择韧带模拟方式、模型网格大小、椎体皮质骨厚度、椎体松质骨材料赋值、椎体小关节摩擦系数、融合器与椎体连接方式六种不同建模因素作为分析对象,根据相关文献中对不同因素的处理方法,采用正交实验设计建立18个有限元模型,比较不同因素对计算结果影响。结果采用融合器上的最大von Mises应力为分析指标时,韧带模拟方法、椎体小关节摩擦系数、融合器与椎体连接方式对计算结果有显著影响;采用椎间融合器最大沉降位移为分析指标时,韧带模拟方式、融合器与椎体连接方式对计算结果有显著影响;在满足一定条件下,网格大小、皮质骨厚度、松质骨材料属性对上述两种指标的影响不显著。结论在本文所研究的腰椎融合器有限元建模的6个因素中,韧带的模拟类型、椎体小关节间摩擦系数、融合器与椎体连接方式是需要重点考虑的因素。本文提出的基于正交实验设计的评价建模因素影响的方法,可以为个性化植入介入器械有限元建模过程的参数优化选择提供参考。     

Preparation of a bonelike apatite-polymer fiber composite using a simple biomimetic process

A bonelike apatite-polymer fiber composite may be useful as an implant material to replace bone, the enthesis of a tendon, and the joint part of a ligament. We treated an ethylene-vinyl alcohol copolymer (EVOH) plate and knitted EVOH fibers with an oxygen plasma to produce oxygen-containing functional groups on their surfaces. The plasma-treated samples were alternately dipped in alcoholic calcium and phosphate ion solutions three times to deposit apatite precursors onto their surfaces. The surface-modified samples formed a dense and uniform bonelike surface apatite layer after immersion for 24 h in a simulated body fluid with ion concentrations approximately equal to those of human blood plasma. The adhesive strength between the apatite layer and the sample's surface increased with increasing power density of the oxygen plasma. The apatite-EVOH fiber composite obtained by our process has similarities to natural bone in that apatite crystals are deposited on organic polymer fibers. The resulting composite would possess osteoconductivity due to the apatite phase. With proper polymer selection and optimized synthesis techniques, a composite could be made that would have bonelike mechanical properties. Hence, the present surface modification and coating process would be a promising route to obtain new implant materials with bonelike mechanical properties and osteoconductivity.     

可吸收性脊柱椎间融合器的理论研究与临床应用

背景：生物可吸收椎间融合器材料具有与骨组织相似的强度及弹性模量,具有射线可透过性,且能随着时间推移逐渐被人体组织吸收替代并更易于融合。 目的：介绍各种可吸收性椎间融合器材料的特点、动物实验以及临床应用效果。 方法：主要选择被PubMed收录的外文文献和在国内核心杂志上发表的有关可吸收性椎间融合器的文献,就其内容进行分析、分类、归纳及总结。 结果与结论：尽管可吸收材料椎间融合器相对于传统椎间融合器来说具有许多优点,目前的实验研究和临床使用也取得了比较满意的结果,但其材料本身属性所致的风险仍然不可忽视,比如pH值降低、存在产生无菌性炎症反应和局部骨吸收的危险等。另外大多数聚合物材料脆性高,由其加工制成的融合器置入人体后可能出现融合器断裂,导致融合失败,尚需逐步发展完善。     

In vivo evaluation of plasma-sprayed wollastonite coating

Wollastonite coatings were prepared by plasma spraying. The bioactivity of wollastonite coatings was investigated in vivo by implanting in dog's muscle, cortical bone and marrow, respectively. The behaviour of bone tissue around wollastonite coatings were examined by histological and SEM observation. After 1 month in the muscle, a bone-like apatite layer was found to form on the surface of the wollastonite coating. When implanted in cortical bone, histological observation demonstrated that bone tissue could extend and grow along the surface of the wollastonite coating. The coating bonded directly to the bone without any fibrous tissue, indicating good biocompatibility and bone conductivity. SEM and EDS analysis revealed that bone did not bond to wollastonite coating directly, but through a Ca/P layer. This suggested that the formation of bone-like apatite layer was very important for bonding to the bone tissue. The amount of bone-implant contact was also measured. Wollastonite coating was shown to stimulate more bone formation on its surface than titanium coating after implantation for 1 month, enhancing the short-term osseointegration properties of implant. The test in marrow indicated that wollastonite coatings could induce new bone formation on their surface showing good bone inductivity property.     

Biomechanical analysis of cages for posterior lumbar interbody fusion

Interbody fusions using intervertebral cages have become increasingly common in spinal surgery. Computational simulations were conducted in order to compare different cage designs in terms of their biomechanical interaction with the spinal structures. Differences in cage design and surgical technique may significantly affect the biomechanics of the fused spine segment, but little knowledge is available on this topic. In the present study, four 3D finite element models were developed, reproducing the human L4-L5 spinal unit in intact condition and after implantation of three different cage models. The intact model consisted of two vertebral bodies and relevant laminae, facet joints, main ligaments and disc. The instrumented models reproduced the post-operative conditions resulting after implant of the different cages. The three considered devices were hollow threaded titanium cages, the BAK (Zimmer Centerpulse, Warsaw, IN, USA), the Interfix and the Interfix Fly (both by Medtronic Sofamor Danek, Memphis, TN, USA). Simulations were run imposing various loading conditions, under a constant compressive preload. A great increase in the stiffness induced on the spinal segment by all cages was observed in all the considered loading cases. Stress distributions on the bony surface were evaluated and discussed. The differences observed between the biomechanics of the instrumented models were associated with the geometrical and surgical features of the devices.     

Dual hydroxyapatite composite with porous and solid parts: experimental study using canine lumbar interbody fusion model

Hydroxyapatite (HA) has been evaluated for use in a variety of applications in bone reconstruction surgery because of its high affinity with host bone and biocompatibility. However, because of the difficulty in combining porosity (for bone ingrowth) and strength in HA, it is generally considered inappropriate to use HA for high-load applications such as spinal interbody fusion. In the present study, we constructed a HA implant for spinal interbody fusion, composed of a dual HA composite (DHC) that combines two HA materials with different porosities: HA with 75% porosity, for bone ingrowth; and HA with 0% porosity, for load bearing. We used a canine lumbar interbody fusion model to evaluate bone conduction of the implant and its efficacy for bony fusion. Six months after the operation, DHC exhibited almost the same efficacy for bony fusion as iliac bone grafts. Moreover, pores of the porous part of the DHC were completely filled with newly formed bone and bone marrow cells. The present findings indicate that DHC is suitable for use as an implant material for spinal interbody fusion as a substitute for iliac bone grafts, which could eliminate the disadvantages associated with autograft harvesting.     

Development of FRP composite structural biomaterials: ultimate strength of the fiber/matrix interfacial bond in in vivo simulated environments.

Fiber reinforced polymer (FRP) composites are being developed as alternatives to metals for structural orthopedic implant applications. FRP composite fracture behavior and environmental interactions are distinctly different from those which occur in metals. These differences must be accounted for in the design and evaluation of implant performance. Fiber/matrix interfacial bond strength in a FRP composite is known to strongly influence fracture behavior. The interfacial bond strength of four candidate fiber/matrix combinations (carbon fiber/polycarbonate, carbon fiber/polysulfone, polyaramid fiber/polycarbonate, polyaramid fiber/polysulfone) were investigated at 37 degrees C in dry and in vivo simulated (saline, exudate) environments. Ultimate bond strength was measured by a single fiber-microdroplet pull-out test. Dry bond strengths were significantly decreased following exposure to either saline or exudate with bond strength loss being approximately equal in both the saline and exudate. Bond strength loss is attributed to the diffusion of water and/or salt ions into the sample and their interaction with interfacial bonding. Because bond degradation is dependent upon diffusion, diffusional equilibrium must be obtained in composite test samples before the full effect of the test environment upon composite mechanical behavior can be determined.     

Porous titanium-nickel for intervertebral fusion in a sheep model: part 1. Histomorphometric and radiological analysis

Porous titanium-nickel (PTN) implants represent an alternative to traditional intervertebral fusion cages. Indeed, PTN materials possess interconnecting pores with cell capillarity properties that may promote bone ingrowth and intervertebral fusion without the need for bone grafting. In this study, a PTN intervertebral fusion device was compared to a conventional TiAlV cage packed with autologous bone in a sheep model. The two devices were implanted at two noncontiguous intervertebral lumbar sites for 3, 6, and 12 months. PTN osseointegration showed a time-dependent trend increasing from 21.4% to 37.6% (3-12 months), whereas TiAlV cages remained at the same level of bone ingrowth (22.7%-25.4%; 3-12 months). Furthermore, PTN bone apposition (10.9%-24.2%; 3-12 months) was significantly higher than that of TiAlV implants (1.1%-5.1%; 3-12 months; p < 0.001, ANOVA). Radiological fusion scores increased with postsurgery time regardless of material type, but were consistently superior for PTN (12.5-18.5; 3-12 months) than for TiAlV cages (2.0-15.0; 3-12 months; p < 0.001, ANOVA). Implant materials were not significantly different according to the radiological interbody index based on preoperative disc height: Interbody index began at 132.6% (PTN) and 123.5% (TiAlV) immediately after surgery, then declined to 80.8% (PTN) and 91.0% (TiAlV) after 12 months. Nevertheless, ungrafted PTN constituted an excellent substrate for osteogenic cell integration and represents a new osteoconductive biomaterial with improved fusion characteristics in comparison to conventional TiAlV cages.