Acid-etched microtexture for enhancement of bone growth into porous-coated implants

We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of bone ingrowth. Cylindrical titanium intramedullary implants were coated with titanium beads to form a porous finish using commercial sintering techniques. A control group of implants was left in the as-sintered condition. The test group was etched in a boiling acidic solution to create an irregular surface over the entire porous coating. Six experimental dogs underwent simultaneous bilateral femoral intramedullary implantation of a control implant and an acid etched implant. At 12 weeks, the implants were harvested in situ and the femora processed for undecalcified, histological examination. Eight transverse serial sections for each implant were analysed by backscattered electron microscopy and the extent of bone ingrowth was quantified by computer-aided image analysis. The extent of bone ingrowth into the control implants was 15.8% while the extent of bone ingrowth into the etched implants was 25.3%, a difference of 60% that was statistically significant. These results are consistent with other research that documents the positive effect of microtextured surfaces on bone formation at an implant surface. The acid etching process developed for this study represents a simple method for enhancing the potential of commonly available porous coatings for biological fixation.     

Hydroxyapatite-coated porous titanium for use as an orthopedic biologic attachment system

The biologic attachment characteristics of hydroxyapatite (HA)-coated porous titanium and uncoated porous titanium implants were investigated. The implants were placed transcortically in the femora of adult mongrel dogs and evaluated after periods of three, six, and 12 weeks. The HA coating was applied using a modified plasma spray process to samples with pore volume and pore size of the porous coating expanded to equal the pore morphology of uncoated porous specimens. Mechanical push-out testing revealed that the bone-porous material interface shear strength increased with time in situ for both the uncoated and HA-coated implants. The use of the HA coating on porous titanium, however, did not significantly increase attachment strength. Histologic and microradiographic sections yielded similar qualitative results in the amount of bone grown into each system. After three weeks, both systems displayed primarily woven bone occupying approximately 50% of the available porous structure. Six and 12 weeks postimplantation, each system displayed more extensive bone ingrowth, organization, and mineralization, with only limited areas of immature bone. Histologically, differences were noted at the ingrown bone-porous material interface between the two implant types. The HA coating supported mineralization directly onto its surface, and a thin osseous layer was found lining all HA-coated surfaces. An extremely thin fibrous layer was observed separating the uncoated titanium particle surface from ingrown bone. There was no extensive direct apposition or lining of the ingrown bone to the uncoated porous titanium particle surfaces.     

Bioactive glass enhances bone ingrowth into the porous titanium coating on orthopaedic implants

Purpose

The aim of the study was to verify the ability of nanoparticulate bioactive glass (BAG) to infiltrate into the porous titanium (Ti) layer on Ti-based implants to promote osseointegration.

Methods

The porous titanium layer on Ti-based implants was impregnated with nanoparticulate BAG. The implants without or with BAG were implanted bilaterally in tibial holes of ten New Zealand white rabbits. The rabbits were sacrificed after ten weeks for examinations. Beside histological examination, EDXS analysis of polished cross-sections of explanted implants was also performed with the aim to quantitatively evaluate the bone-to-pore contact and bone-in-pore ratio.

Results

After ten weeks, EDXS analyses of cross-sections of the explanted implants confirmed that bioactive glass was fully resorbed and that the pores throughout the thickness of the porous titanium layer were to a large extent filled with a new bone. In the absence of bioactive glass, only the outer part of the porous layer was filled with bone. The implants without BAG in the porous Ti-layer exhibited similar bone-to-pore contact, while significant improvement of bone ingrowth into the pores was observed for the implants with BAG (38%), as opposed to those without it (22%).

Conclusion

This study confirmed that the nanoparticulate bioactive glass within the porous titanium surface layer on implants promotes osseointegration and stimulates the formation of bone within the pores.     

A porous bioactive titanium implant for spinal interbody fusion: an experimental study using a canine model

OBJECT: Porous biomaterials with adequate pore structure and appropriate mechanical properties are expected to provide a new generation of devices for spinal interbody fusion because of their potential to eliminate bone grafting. The purpose of this study was to evaluate the fusion characteristics of porous bioactive titanium implants using a canine anterior interbody fusion model. METHODS: Porous titanium implants sintered with volatile spacer particles (porosity 50%, average pore size 303 microm, compressive strength 116.3 MPa) were subjected to chemical and thermal treatments that give a bioactive microporous titania layer on the titanium surface (BT implant). Ten adult female beagle dogs underwent anterior lumbar interbody fusion at L6-7 using either BT implants or nontreated (NT) implants, followed by posterior spinous process wiring and facet screw fixation. Radiographic evaluations were performed at 1, 2, and 3 months postoperatively using X-ray fluoroscopy. Animals were killed 3 months postoperatively, and fusion status was evaluated by manual palpation and histological examination. RESULTS: Interbody fusion was confirmed in all five dogs in the BT group and three of five dogs in the NT group. Histological examination demonstrated a large amount of new bone formation with marrowlike tissue in the BT implants and primarily fibrous tissue formation in the NT implants. CONCLUSIONS: Bioactive treatment effectively enhanced the fusion ability of the porous titanium implants. These findings, coupled with the appropriate mechanical properties in load-bearing conditions, indicate that these porous bioactive titanium implants represent a new generation of biomaterial for spinal interbody fusion.     

Spine Interbody Implants: Material Selection and Modification,Functionalization and Bioactivation of Surfaces to Improve Osseointegration

The clinical outcome of lumbar spinal fusion is correlated with achievement of bony fusion. Improving interbody implant bone on‐growth and in‐growth may enhance fusion, limiting pseudoarthrosis, stress shielding, subsidence and implant failure. Polyetheretherketone (PEEK) and titanium (Ti) are commonly selected for interbody spacer construction. Although these materials have desirable biocompatibility and mechanical properties, they require further modification to support osseointegration. Reports of extensive research on this topic are available in biomaterial‐centric published reports; however, there are few clinical studies concerning surface modification of interbody spinal implants. The current article focuses on surface modifications aimed at fostering osseointegration from a clinician's point of view. Surface modification of Ti by creating rougher surfaces, modifying its surface topography (macro and nano), physical and chemical treatment and creating a porous material with high interconnectivity can improve its osseointegrative potential and bioactivity. Coating the surface with osteoconductive materials like hydroxyapatite (HA) can improve osseointegration. Because PEEK spacers are relatively inert, creating a composite by adding Ti or osteoconductive materials like HA can improve osseointegration. In addition, PEEK may be coated with Ti, effectively bio‐activating the coating.     

Influence of disodium (1-hydroxythylidene) diphosphonate on bone ingrowth into porous,titanium fiber-mesh implants

The influence of disodium (1-hydroxythylidene) diphosphonate on the bonding between bone and porous, titanium fiber-mesh implants was studied. Rectangular, porous, titanium fiber-mesh implants (15 × 10 × 2.4 mm) were implanted into the tibial bone of mature male rabbits. The rabbits were divided into six groups. Disodium diphosphonate was administered daily by subcutaneous injection to groups 1–5. Groups 1–4 received doses of 5.0, 2.5, 1.0, and 0.1 mg per kilogram of body weight per day for 8 weeks, respectively. Group 5 received a dose of 5 mg per kilogram of body weight per day for 4 weeks. Group 6 (control group) was given saline injections. At 8 weeks after implantation, the rabbits were killed. The tibiae containing the implants were dissected out and subjected to detachment tests. The failure load, when an implant became detached from the bone or when the bone itself broke, was measured. The interface of the bone and implant was investigated by Giemsa surface staining and contact microradiography. Giemsa surface staining and contact microradiography showed that porous implant bonding to bone tissue was inhibited by a high dose of disodium diphosphonate in groups 1, 2, and 5. Soft tissue was observed at the interface. In groups 3, 4, and 6, bone tissue ingrowth was observed at the interface between the porous implant and bone tissue. Growth of bone into the porous fiber-mesh implant of a cementless prosthesis is possible if a low dose of diphosphonate below 1.0 mg per kilogram of body weight is given subcutaneously     

Covalently‐linked hyaluronan promotes bone formation around Ti implants in a rabbit model

The goal of this study was the in vivo evaluation of nanoporous titanium (Ti) implants bearing a covalently linked surface hyaluronan (HA) layer. Implant surface topography and surface chemistry were previously evaluated by scanning electron micorscopy and X‐ray photoelectron spectroscopy. Results showed that the surface modification process did not affect surface topography, yielding a homogeneously HA‐coated nanotextured implant surface. In vivo evaluation of implants in both cortical and trabecular bone of rabbit femurs showed a significant improvement of both bone‐to‐implant contact and bone ingrowth at HA‐bearing implant interfaces at 4 weeks. The improvement in osteointegration rate was particularly evident in the marrow‐rich trabecular bone (bone‐to‐implant contact: control 22.5%; HA‐coated 69.0%, p < 0.01). Mechanical testing (push‐out test) and evaluation of interfacial bone microhardness confirmed a faster bone maturation around HA‐coated implants (Bone Maturation Index: control 79.1%; HA‐coated 90.6%, p < 0.05). Suggestions based on the biochemical role of HA are presented to account for the observed behavior. Published by Wiley Periodicals, Inc. J Orthop Res 27: 657–663, 2009     

Comparison with the osteoconductivity and bone-bonding ability of the iodine supported titanium,titanium with porous oxide layer and the titanium alloy in the rabbit model

Background

One of the serious postoperative complications associated with joint replacement is bacterial infection. In our recent investigations, iodine supported titanium implants demonstrated antibacterial activity in both in vitro and in vivo studies. The surfaces of the implants have porous anodic oxide layer with the antiseptic properties of iodine. According to the literature the titanium with porous anodic oxide have good osteoconductivity. But it is not clear whether the properties of iodine influence bone bonding of implants.

The relevance of hydroxyapatite and spongious titanium coatings in fixation of cementless stems

Pure titanium rods plasma-spray coated with hydroxyapatite (HA) or porous titanium (Ti) of controlled roughness were implanted bilaterally in the distal femur of Sprague-Dawley rats to compare the extent of bone growth on the two types of coating. The relevance of other factors, like mechanical stability and biological adaptation of the bone to the insertion of a foreign body implant, were investigated in femora which were over-reamed (absence of primary fit) or reamed without insertion of the rod. Continuous tetracycline labeling for the first 30 days and for the last 2 weeks in the 90-day group was performed; histological/histometric, fluorescence and microangiographic studies were carried out on serial sections of the implanted and control femora. In the group of stable implants, HA-coated rods showed 90% integration versus 53% with Ti-coated implants (P < 0.001); in over-reamed implants neither surface bone growth nor endosteal fixation occurred, and both types of rods were surrounded by a thick layer of connective tissue. The study documented early adhesion of osteoblasts and direct deposition of bone matrix on the substrate, while on spongious titanium osteogenesis was observed only in proximity to the surface. Remodeling of the reactive, primary bone to mature, lamellar bone took the form of a capsule surrounding the implants and radial bridges connecting the latter to the endosteal surface. The number, height and thickness of these bridges appeared to be the factors determining implant stability, rather than the extent of the bony capsule on the perimeter of the implant. Integration was a function not only of mechanical conditions and surface geometry, but also of the biological response of the whole bone to changes in the vascularization pattern. The reported phenomena can be seen more easily in experimental models involving small rodents because of their fast bone turnover and revascularization, but it is expected that they take place, even at a lower speed, in clinical situations like cementless stems of total hip replacement. Received: 22 August 1995     

Analysis of performance of root-form endosseous implants placed in the maxillary sinus

To evaluate the long-term effect on metal-bone interface of the perforation of the maxillary antral floor by root-form titanium implants, a study was undertaken in five mature Macaca fascicularis monkeys. One root-form titanium implant was placed bilaterally in the maxillary sinus perforating the sinus 5 mm and a second implant was placed completely in bone tissue. The protruding implant in the right antrum was grafted with autogenous cancellous bone and porous bone mineral (Bio-Oss) and the contralateral antral implant protruding in the antrum was left without grafting. The bilateral implants were used to support "free-standing" fixed prostheses, which were in full function for 14 months, during which time there was excellent clinical function and no mobility of the implants. Histomorphometric analysis of specimens revealed that there was no difference in the trabecular pattern or the amount of calcified matrix vs. marrow vascular spaces along the titanium implant interface. New reparative bone partially restored the osseous surface along the implant on the ungrafted side. Implants in the grafted antrum demonstrated bone regeneration over the implant surface ranging from 2 cm to complete regeneration. Histomorphometric analysis revealed the peri-implant bone to contain some particles of the Bio-Oss, although most of the implant bone interface exhibited only vital bone and marrow vascular spaces. The study indicates that the protrusion of implants maximally into the sinus floor does not necessarily require a bone graft to produce functional abutments for fixed prostheses and that implants can function well with 5 mm of protrusion into the antrum with excellent bone-metal interface.     

Influence of biomaterial structure and hardness on its osseo-integration: histomorphometric evaluation of porous nitinol and titanium implants

The aim of this research was to evaluate and compare the bone integration and apposition capacities of two metallic intervertebral fusion implants, porous nitinol (PNT: porous Nickel Titanium Naval Ordonance Laboratory) and titanium intervertebral cage, in the sheep lumbar spine. Sixteen sheep received two implants each at L2–L3 and L4–L5 lumbar levels so as to subject both the implants to the same mechanical loads. The sheep were then sacrificed at 3, 6 and 12 months post-implantation periods. Lumbar segments were then harvested. A qualitative (macroscopic and microscopic observation) and quantitative (histomorphometric) analysis of bone integration and apposition was carried out on histological slides. The results indicated that the PNT obtained the better bone integration and apposition compared to titanium cage. The osseo-integration of each implant seemed to be influenced by its structure and its hardness. However, the biocompatibility of two implants seemed comparable.     

Hydroxyapatite coating modifies implant membrane formation. Controlled micromotion studied in dogs.

We studied the influence of controlled micromovements between bone and porous titanium alloy implants with and without hydroxyapatite coating. A dynamically loaded unstable device producing approximately 150-microns axial translation of knee implants during each gait cycle was developed. Stable implants served as controls. Matched stable and unstable implants with either porous titanium (Ti) or hydroxyapatite (HA) coating surrounded by a gap of 0.75 mm were inserted into the weight-bearing regions of the medial femoral condyles in 14 mature dogs. Histologic analysis after 4 weeks showed a fibrous membrane surrounding both types of implants subjected to micromovements, whereas various amounts of bone ingrowth was obtained in the stable implants. The membrane around unstable HA implants was thinner than that around unstable Ti implants. Islands of fibrocartilaginous tissue characterized the membrane around unstable HA implants, whereas fibrous connective tissue surrounded unstable Ti implants. The collagen concentration of the fibrous membranes was higher around unstable HA implants compared with Ti implants. Instability reduced the shear strength of the implants. However, the shear strength of unstable HA implants exceeded that of the Ti implants, both unstable and stable. The greatest shear strength was obtained by stable HA implants, i.e., tenfold greater than that of stable Ti implants. The gap-healing capacity around stable HA implants increased toward the HA surface, and was greater than that around Ti implants. Our study demonstrates that micromovements between bone and implant inhibit bone ingrowth and lead to the development of a fibrous membrane. The superior fixation of unstable HA implants compared with unstable Ti implants may be ascribed to the presence of fibrocartilage, a higher collagen concentration, and radiating orientation of collagen fibers in the membrane. The strongest mechanical anchorage and the greatest amount of bone ingrowth was obtained by stable implants coated with hydroxyapatite.     

Comparison of 3D-printed titanium-alloy,standard titanium-alloy,and PEEK interbody spacers in an ovine model

BACKGROUND CONTEXTOsseointegration is a pivotal process in achieving a rigid fusion and ultimately a successful clinical outcome following interbody fusion surgery. Advancements in 3D printing technology permit commonly used titanium interbody spacers to be designed with unique architectures, such as a highly interconnected and specific porous structure that mimics the architecture of trabecular bone. Interbody implants with a microscale surface roughness and biomimetic porosity may improve bony ongrowth and ingrowth compared to traditional materials.PURPOSEThe purpose of this study was to compare the osseointegration of lumbar interbody fusion devices composed of surgical-grade polyetheretherketone (PEEK), titanium-alloy (TAV), and 3D-printed porous, biomimetic TAV (3DP) using an in vivo ovine model.STUDY DESIGNIn Vivo Preclinical Animal StudyMETHODSEighteen sheep underwent two-level lateral lumbar interbody fusion randomized with either 3DP, PEEK, or TAV interbody spacers (n=6 levels for each spacer per time point). Postoperative time points were 6 and 12 weeks. Microcomputed tomography and histomorphometry were used to quantify bone volume (BV) within the spacers (ingrowth) and the surface bone apposition ratio (BAR) (ongrowth), respectively.RESULTSThe 3DP-treatment group demonstrated significantly higher BV than the PEEK and TAV groups at 6 weeks (77.3±44.1 mm³, 116.9±43.0 mm³, and 108.7±15.2 mm³, respectively) (p<.05). At 12 weeks, there were no BV differences between groups (p>.05). BV increased in all groups from the 6- to 12-week time points (p<.05). At both time points, the 3DP-treated group (6w: 23.6±10.9%; 12w: 36.5±10.9%) had significantly greater BAR than the PEEK (6w: 8.6±2.1%; 12w: 14.0±5.0%) and TAV (6w: 6.0±5.7%; 12w: 4.1±3.3%) groups (p<.05).CONCLUSIONS3DP interbody spacers facilitated greater total bony ingrowth at 6 weeks, and greater bony ongrowth postoperatively at both 6 and 12 weeks, in comparison to solid PEEK and TAV implants.CLINICAL SIGNIFICANCEBased on these findings, the 3DP spacers may be a reasonable alternative to traditional PEEK and TAV spacers in various clinical applications of interbody fusion.     

Metallic Biomaterials in Skeletal Repair

Abstract Metallic biomaterials are becoming increasingly important in skeletal repair. The goal of this review article is to present an overview of metallic implant materials currently used in trauma and orthopedic surgery. Further, new research trends and future clinical concepts are described and discussed. Titanium, titanium alloys, stainless steels and CoCr alloys are used as bone implants in orthopedic and trauma surgery. Especially titanium and its alloys currently constitute the most highly favoured implant materials for joint replacement and osteosynthesis. In comparison to other metallic implant materials, titanium is characterized by a high biocompatibility, a good workability and corrosion resistance with suitable mechanical properties (low Young’s modulus—high strength). To improve orthopedic implants, there is a trend in current research towards the development of new titanium alloys with improved biological and biomechanical properties. To achieve a fast and safe bone fixation of the implants, optimized surface characteristics and surface structures are applied. Biomimetic coatings with and without the ability to release growth factors and cell coatings even including the development of stem-cell-coated titanium implants for the partial surface replacement of joints are under investigation.     

Healing in peri‐implant gap with BMP‐2 and systemic bisphosphonate is dependent on BMP‐2 dose—A canine study

The bone–implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone–implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone morphogenetic protein 2 (BMP‐2) stimulates osteoblast formation to increase new bone formation but also indirectly stimulates osteoclast activity. In this experiment, we investigate the hypothesis that osseointegration, defined as mechanical push‐out and histomorphometry, depends on the dose of BMP‐2 when delivered as an anabolic agent with systemic administration of the anti‐resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface‐applied BMP‐2 (15 µg; 60 µg; 240 µg) and untreated) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered 10 days into the observation period of 4 weeks. Bone–implant specimens were evaluated by mechanical push‐out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg implants. The results in a canine implant model demonstrated that a narrow range of BMP‐2 doses have opposite effects in bridging an empty peri‐implant gap with bone, when combined with systemic zoledronate. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406–1414, 2018.

     

Effects of surface roughness of titanium implants on bone remodeling activity of femur in rabbits

We investigated the bone remodeling activity on titanium implants with different surface roughnesses using a confocal laser scanning microscope (CLSM). Two kinds of implants were used, the machined smooth-surfaced titanium and the plasma-sprayed rough-surfaced titanium. These implants were randomly inserted in a rabbit's femur from the lateral aspect of the diaphysis bicortically. Rabbits were killed at 6, 16, and 42 weeks after surgery. The implant-bone blocks were embedded in polyester resin, and were prepared to make undecalcified ground sections. Histomorphometric analyses were performed at the cortical bone-implant interface using the image obtained by CLSM. Percentages of direct bone-implant contact and bone volume (BV/TV) around the implant was greater in rough-surfaced titanium compared with the smooth-surfaced titanium at 42 weeks after implantation. On the contrary, the eroded surface (ES/BS) appeared to be less in the rough-surfaced titanium than in the smooth-surfaced titanium at 6 weeks after implantation, but thereafter, no difference was found between the two kinds of implants. Mineralizing surface (MS/BS) and mineral apposition rate (MAR) showed no significant differences throughtout the experimental period. These results indicate that increased bone volume in the rabbits of rough-surfaced titanium implants is due to less remodeling activity during the early stage after implantation compared with the smooth-surfaced implants. The surface roughness of titanium is one factor which helps in determining the balance between bone formation and resorption of remodeling at the interface of the bone implants.     

五种多孔生物陶瓷支架的肌肉植入实验研究

 目的 观察多孔生物玻璃(Bioglass)、β-磷酸三钙(β-tricalcium phosphate, β-TCP)、羟基 磷灰石(hydroxyapatite, HA)、β-硅酸钙(β-calcium silicate, β-CS)、α-硅酸钙(α-CS)五种生物陶瓷支架 植入家兔肌肉的生物学表现。 方法应用添加造孔剂工艺烧结制备得到多孔Bioglass、β-TCP、HA、β-CS 和α-CS 支架, 通过X 线衍射、孔隙率测定、生物力学测定进行特征分析。将五种支架植入家兔背部肌肉 中, 4、8、12、16 周取材, 通过X线、Micro-CT、组织学、扫描电镜和能谱分析进行观察分析, 并取材与支架 接触肌肉进行聚合酶链式反应(polymerase chain reaction, PCR)分析骨形态发生蛋白-2 (bone morphogenetic protein-2, BMP-2)和BMP-7 含量。 结果 五种支架特征分析表明, 抗压强度:Bioglass>α-CS>βCS>β-TCP>HA;弹性模量:α-CS α-CS>β-TCP>Bioglass> HA。组织学观察五种支架中均未出现新生骨组织。Bioglass、α-CS、β-CS 表面有钙磷层形成, 说明具有体 内生物活性。16 周时, 只有β-CS 出现BMP-2和BMP-7 表达。 结论 多孔硅酸钙支架具有良好体内生 物活性、可降解性, 但无体内骨诱导性。     

Ectopic bone formation by composites of BMP and metal implants in rats

Disc-shaped implants of titanium alloy (Ti-6AI-4V) were treated on one side by corundum-blasting (CB) or by coating with hydroxyapatite (HA) or pure titanium (Ti) using plasma spraying. Half of the implants were additionally coated with purified swine BMP-3. The composites and the uncoated controls were implanted into abdominal wall-muscle pouches of rats. 25 days after implantation, ectopic bone formation could be observed macroscopically and histologically in a high frequency in all 3 groups of BMP-coated implants, whereas the controls were constantly inactive. The volumes of induced bone were similar for BMP-3-coated pure Ti and HA implants, while CB implants were significantly less active. Our findings indicate that the bone formation process is influenced by the chemical composition and by the structure of the implant surface.