Influence of porosity on mechanical properties and in vivo response of Ti6Al4V implants

Metallic biomaterials are widely used to restore the lost structure and functions of human bone. Due to the large number of joint replacements, there is a growing demand for new and improved orthopedic implants. More specifically, there is a need for novel load-bearing metallic implants with low effective modulus matching that of bone in order to reduce stress shielding and consequently increase the in vivo lifespan of the implant. In this study, we have fabricated porous Ti6Al4V alloy structures, using laser engineered net shaping (LENS?), to demonstrate that advanced manufacturing techniques such as LENS? can be used to fabricate low-modulus, tailored porosity implants with a wide variety of metals/alloys, where the porosity can be designed in areas based on the patient’s need to enhance biological fixation and achieve long-term in vivo stability. The effective modulus of Ti6Al4V alloy structures has been tailored between 7 and 60 GPa and porous Ti alloy structures containing 23–32 vol.% porosity showed modulus equivalent to human cortical bone. In vivo behavior of porous Ti6Al4V alloy samples in male Sprague–Dawley rats for 16 weeks demonstrated a significant increase in calcium within the implants, indicating excellent biological tissue ingrowth through interconnected porosity. In vivo results also showed that total amount of porosity plays an important role in tissue ingrowth.     

Hybrid bone implants: self-assembly of peptide amphiphile nanofibers within porous titanium

Over the past few decades there has been great interest in the use of orthopedic and dental implants that integrate into tissue by promoting bone ingrowth or bone adhesion, thereby eliminating the need for cement fixation. However, strategies to create bioactive implant surfaces to direct cellular activity and mineralization leading to osteointegration are lacking. We report here on a method to prepare a hybrid bone implant material consisting of a Ti-6Al-4V foam, whose 52% porosity is filled with a peptide amphiphile (PA) nanofiber matrix. These PA nanofibers can be highly bioactive by molecular design, and are used here as a strategy to transform an inert titanium foam into a potentially bioactive implant. Using scanning electron microscopy (SEM) and confocal microscopy, we show that PA molecules self-assemble into a nanofiber matrix within the pores of the metallic foam, fully occupying the foam's interconnected porosity. Furthermore, the method allows the encapsulation of cells within the bioactive matrix, and under appropriate conditions the nanofibers can nucleate mineralization of calcium phosphate phases with a Ca:P ratio that corresponds to that of hydroxyapatite. Cell encapsulation was quantified using a DNA measuring assay and qualitatively verified by SEM and confocal microscopy. An in vivo experiment was performed using a bone plug model in the diaphysis of the hind femurs of a Sprague Dawley rat and examined by histology to evaluate the performance of these hybrid systems after 4 weeks of implantation. Preliminary results demonstrate de novo bone formation around and inside the implant, vascularization around the implant, as well as the absence of a cytotoxic response. The PA-Ti hybrid strategy could be potentially tailored to initiate mineralization and direct a cellular response from the host tissue into porous implants to form new bone and thereby improve fixation, osteointegration, and long term stability of implants.     

Bone response to a novel highly porous surface in a canine implantable chamber

Long-term survival of uncemented hip components is dependent upon successful biological fixation. This study examined a new prosthetic surface treatment consisting of a highly porous open structure of commercially pure titanium, Tritanium Dimensionalized Metal; its overall porosity is approximately 65-70%. With the use of an implantable chamber in dogs, the effects of this treatment on bone ingrowth and strength of attachment were compared to both titanium (overall porosity of 30-35%) and cobalt chrome beads (overall porosity of 35-40%), with and without hydroxyapatite coating. At 6 and 12 weeks, chambers were explanted and specimens underwent high-resolution radiographic imaging and mechanical testing. At 12 weeks, Tritanium surfaces had greater bone penetration and tensile strength than remaining surface types. Over 40% of the Tritanium specimens had a tensile strength greater than 500 N, exceeding the testing capability of the servohydraulic equipment. The highly porous Tritanium surfaces allow for a far greater amount of bone ingrowth than beaded surfaces, and may create a geometry that enhances mechanical strength. Tritanium Dimensionalized Metal surface treatment may result in a clinically valuable implant fixation surface to induce rapid ingrowth and a strong bone-implant interface, contributing to increased implant survivorship.     

Tissue ingrowth and degradation of two biodegradable porous polymers with different porosities and pore sizes

Commonly, spontaneous repair of lesions in the avascular zone of the knee meniscus does not occur. By implanting a porous polymer scaffold in a knee meniscus defect, the lesion is connected with the abundantly vascularized knee capsule and healing can be realized. Ingrowth of fibrovascular tissue and thus healing capacity depended on porosity, pore sizes and compression modulus of the implant. To study the lesion healing potential, two series of porous polyurethanes based on 50/50 epsilon-caprolactone/L-lactide with different porosities and pore sizes were implanted subcutaneously in rats. Also, in vitro degradation of the polymer was evaluated. The porous polymers with the higher porosity, more interconnected macropores, and interconnecting micropores of at least 30 microm showed complete ingrowth of tissue before degradation had started. In implants with the lower macro-porosity and micropores of 10-15 microm degradation of the polymer occurred before ingrowth was completed. Directly after implantation and later during degradation of the polymer, PMN cells infiltrated the implant. In between these phases the foreign body reaction remained restricted to macrophages and giant cells. We can conclude that both foams seemed not suited for implantation in meniscal reconstruction while either full ingrowth of tissue was not realized before polymer degradation started or the compression modulus was too low. Therefore, foams must be developed with a higher compression modulus and more connections with sufficient diameter between the macropores.     

Stress distribution in porous surfaced medullary implants

Finite element stress analysis has been applied to examine the stress patterns in a prosthesis requiring fixation in the medullary shaft of a long bone. No specific prosthesis is considered but rather a generally applicable geometry has been chosen. This consists of a cylindrical section of cortical bone within which is implanted a prosthesis composed of a solid central rod surrounded by a porous coating. The finite element analysis utilized an axisymmetric model to determine the distribution of stresses throughout the system. The effect of changes in length of prosthesis, thickness of porous coating, depth and type of tissue ingrowth, and type of porous coating material were studied under conditions of axisymmetric loading. The results indicate that with complete bone ingrowth, the maximum shear stress and the distance necessary for load transfer are both independent of implant length. However, with incomplete ingrowth, increasing implant length reduces shear. Incomplete growth also produces lower shear stresses but higher shear strains in areas without ingrowth. In addition, a porous polyethylene coating gives a more even load transfer and lower shear than a porous coating of a high modulus material.     

Cellular Ti-6Al-4V structures with interconnected macro porosity for bone implants fabricated by selective electron beam melting

Selective electron beam melting (SEBM) was successfully used to fabricate novel cellular Ti-6Al-4V structures for orthopaedic applications. Micro computer tomography (muCT) analysis demonstrated the capability to fabricate three-dimensional structures with an interconnected porosity and pore sizes suitable for tissue ingrowth and vascularization. Mechanical properties, such as compressive strength and elastic modulus, of the tested structures were similar to those of human bone. Thus, stress-shielding effects after implantation might be avoided due to a reduced stiffness mismatch between implant and bone. A chemical surface modification using HCl and NaOH induced apatite formation during in vitro bioactivity tests in simulated body fluid under dynamic conditions. The modified bioactive surface is expected to enhance the fixation of the implant in the surrounding bone as well as to improve its long-term stability.     

Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures

Calcium phosphate cement (CPC) is highly promising for clinical uses due to its in situ-setting ability, excellent osteoconductivity and bone-replacement capability. However, the low strength limits its use to non-load-bearing applications. The objectives of this study were to develop a layered CPC structure by combining a macroporous CPC layer with a strong CPC layer, and to investigate the effects of porosity and layer thickness ratios. The rationale was for the macroporous layer to accept tissue ingrowth, while the fiber-reinforced strong layer would provide the needed early-strength. A biopolymer chitosan was incorporated to strengthen both layers. Flexural strength, S (mean+/-sd; n=6) of CPC-scaffold decreased from (9.7+/-1.2) to (1.8+/-0.3) MPa (p<0.05), when the porosity increased from 44.6% to 66.2%. However, with a strong-layer reinforcement, S increased to (25.2+/-6.7) and (10.0+/-1.4) MPa, respectively, at these two porosities. These strengths matched/exceeded the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. Relationships were established between S and the ratio of strong layer thickness/specimen thickness, a/h:S=(17.6 a/h+3.2) MPa. The scaffold contained macropores with a macropore length (mean+/-sd; n=147) of (183+/-73) microm, suitable for cell infiltration and tissue ingrowth. Nano-sized hydroxyapatite crystals were observed to form the scaffold matrix of CPC with chitosan. In summary, a layered CPC implant, combining a macroporous CPC with a strong CPC, was developed. Mechanical strength and macroporosity are conflicting requirements. However, the novel functionally graded CPC enabled a relatively high strength and macroporosity to be simultaneously achieved. Such an in situ-hardening nano-apatite may be useful in moderate stress-bearing applications, with macroporosity to enhance tissue ingrowth and implant resorption.     

Mechanical and in vivo performance of hydroxyapatite implants with controlled architectures.

Internal architecture has a direct impact on the mechanical and biological behaviors of porous hydroxyapatite (HA) implant. However, traditional processing methods provide minimal control in this regard. To address the issue, we developed a new processing method combining image-based design and solid free-form fabrication. We have previously published the processing method showing fabricated HA implants and their chemical properties. This study characterized the mechanical and the in vivo performance of designed HA implants. Thirteen HA implants with orthogonal channels at 40% porosity were tested on an Instron machine. The compressive strength and compressive modulus measured were 30+/-8 MPa and 1.4+/-0.4 GPa, comparable to coralline porous HA. Twenty-four cylindrical HA implants with two architecture designs, orthogonal and radial channels, were implanted in the mandibles of four Yucatan minipigs for 5 and 9 weeks. Normal bone regeneration occurred in both groups. At 9 weeks, bone penetrated 1.4mm into both scaffold designs. The percent bone ingrowth in the penetration zone was higher in the orthogonal channel design but not statistically different due to the low number of samples. However, the overall shape of the regenerated bone tissue was significantly different. In the orthogonal design, bone and HA formed an interpenetrating matrix, while in the radial design, the regenerated bone formed an intact piece at the center of the implant. These preliminary results showed that controlling the overall geometry of the regenerated bone tissue is possible through the internal architectural design of the scaffolds.     

基于SLM成形的下颌骨植入物固定板力学性能

目的 利用拓扑优化确定最优下颌骨植入物固定板的布局,并设计高承载能力的个性化下颌骨植入物固定板。 方法 以典型的下颌骨缺损模型为例,构建考虑骨骼和支架材料特性的下颌骨有限元模型。 对模型进行拓扑优化分析,设计个性化下颌骨植入物固定板。 通过模拟分析常规固定板系统与个性化固定板系统下颌骨、固定板、 螺钉的应力分布,评估个性化下颌骨植入物固定板的力学特性。 并结合 Gibson-Ashby 模型,设计弹性模量与皮质骨相当的多孔面心立方晶格结构假体,最终确定最终支架方案。 结果 通过安装个性化下颌骨植入物固定板,下颌骨、接骨板、螺钉的峰值应力分别 55. 86、291. 1、122. 53 MPa,分别比安装常规固定板降低 9. 8% 、32. 0% 和14. 6% 。 结合个性化下颌骨植入物固定板与多孔结构的设计方案,得到最优孔隙率为 71. 6% 的三维多孔支架模型。 结论 本研究设计的个性化下颌骨植入物固定板显著降低假体的峰值应力,提高支架的可靠性。 并且结合激光选区熔化(selective laser melting, SLM)技术,可以快速制造出性能优异的个性化假体,以满足紧迫的时间需求。     

Bone apposition to plasma-sprayed cobalt-chromium alloy.

The use of porous metallic coatings for fixation of total joint prostheses by bone ingrowth has become a widespread alternative to fixation with PMMA bone cement. However, concerns about such coatings include long-term effects of metal ion release, potential coating loss, and decreased substrate fatigue strength. The biological fixation capability of a nonporous, high-integrity plasma-sprayed CoCr coating with low surface area was compared to a conventional sintered bead coating in goat cortical and cancellous bone sites after 8 and 16 weeks of implantation. Histological evaluation showed substantial variations in fixation quality between individual animals and between surgical sites with no consistent difference between implant types. Shear testing of bone/implant interfaces showed that although conventional porous coating exhibited higher overall average shear strengths in cortical bone sites at both time periods, the differences were not statistically significant. In cancellous sites, the average shear strengths achieved with conventional porous and plasma-sprayed coatings were essentially equal. Analysis using average paired differences, however, revealed that when porous and plasma-coated implants are placed in identical sites of contralateral limbs, the plasma coatings consistently yielded higher shear strengths in cancellous bone sites at the later time period. Since current design theory for biological fixation favors metaphysical fixation, this surface may offer potential advantages over conventional porous coatings.     

The structure of the bond between bone and porous silicon-substituted hydroxyapatite bioceramic implants

The significance of micrometer-sized strut porosity in promoting bone ingrowth into porous hydroxyapatite (HA) scaffolds has only recently been noted. In this study, silicon-substituted HA (0.8 wt % Si-HA) with approximately 8.5% of the total porosity present as microporosity within the struts of the implant was prepared for high-resolution transmission electron microscopy (HR-TEM) via both ultramicrotomy and focused ion beam milling. Between the struts of the porous Si-HA, pores with varying shapes and sizes (1-10 microm in diameter) were characterized. Within the struts, the Si-HA contained features such as grain boundaries and triple-junction grain boundaries. Bone ingrowth and dissolution from a Si-HA implant were studied using HR-TEM after 6 weeks in vivo. Minor local dissolution occurred within several pores within the struts. Organized, mineralized collagen fibrils had grown into the strut porosity at the interface between the porous Si-HA implant and the surface of the surrounding bone. In comparison, deeper within the implant, disorganized and poorly mineralized fibers were observed within the strut porosity. These findings provide valuable insight into the development of bone around porous Si-HA implants.     

Preliminary observations of bone ingrowth into porous materials.

A preliminary investigation has been performed (a) to determine the kinetics of bone ingrowth into porous materials and to determine if this ingrowth could be catalyzed by the presence of a foreign substrate; and (b) to measure the bonding capability of bone with a porous-surfaced metallic implant. Tests on porous-surfaced implants corroborate the work of other investigators in showing that bony tissue will grow into a porous substance that has pores large enough to support tissue nourishment. The shear strength of the bone-implant interface appears to increase with pore size and time of healing. Furthermore, it may be possible to catalyze this tissue ingrowth by the introduction into the fracture site of a foreign substance; in this experiment, glass beads 200-290mu in diameter were used.     

Orthopedic prosthesis fixation

The fixation of orthopedic implants has been one of the most difficult and challenging problems. The fixation can be achieved via: (a) direct mechanical fixation using screws, pins, wires, etc.; (b) passive or interference mechanical fixation where the implants are allowed to move or merely positioned onto the tissue surfaces; (c) bone cement fixation which is actually a grouting material; (d) biological fixation by allowing tissues to grow into the interstices of pores or textured surfaces of implants; (e) direct chemical bonding between implant and tissues; or (f) any combination of the above techniques. This article is concerned with various fixation techniques including the potential use of electrical, pulsed electromagnetic field chemical stimulation using calcium phosphates for the enhancement of tissue ingrowth, direct bonding with bone by glass-ceramics and resorbable particle impregnated bone cement to take advantages of both the immediate fixation offered by the bone cement and long term fixation due to tissue ingrowth.     

Novel production method and in-vitro cell compatibility of porous Ti-6Al-4V alloy disk for hard tissue engineering

Porous metals are attractive due to its unique physical, mechanical, and new bone tissue ingrowth properties. In the present study, the production of highly porous Ti-6Al-4V parts by powder metallurgical technology and subsequently it's uses in in vitro bone tissue engineering is described. A space-holder method using carbamide with different particle size to produce parts with porosities between 35 and 70% were applied. The compressive strength and Young's modulus of porous Ti-6Al-4V were determined. Results indicated that stress and Young's modulus decrease with increasing porosity and pore size. The porous parts are characterized by scanning electron microscopy. Furthermore, study was to investigate the effects of three different porosities of porous Ti-6Al-4V (35, 50, and 70%) on proliferation, differentiation, and cell-matrix interaction of mouse osteoblast-like cells, MC-3T3. Results showed that the cell proliferation was significantly (p < 0.05) higher on 70% porous Ti-6Al-4V. However, synthesis of different types of extra cellular matrix proteins was also more abundant on 70% porous Ti-6Al-4V than 35 and 50% porous Ti-6Al-4V disk except some specific proteins. An increase in alkaline phosphate activity was significantly (p < 0.05) higher on 70 and 50% porous Ti-6Al-4V disk after 12 days of MC-3T3 cells incubation. Above all, results indicated that porosity (nearly 70%) of porous Ti-6Al-4V topography affects proliferation and differentiation of osteoblast-like MC-3T3 cells. The results showed that this novel process is a promise to fabricate porous biomaterials for bone implants.     

No effect of a type I collagen gel coating in uncemented implant fixation

Uncemented joint replacement with a variety of substrate materials, structures, and coatings are commonplace in arthroplasty. Even with specialized surgical preparation of bone, intimate contact between the implant and host bone may not always be achieved. This study evaluated the in vivo effect of fibrillar atelopeptide and PEG crosslinked collagens coatings placed directly into porous sintered bead structures on bone ingrowth using a skeletally mature bicortical, bilateral ovine tibia model. Bone ingrowth into the implants increased with time, although differences were not significant. At 4 weeks woven bone was present within the pores that remodeled with time. Significantly lower levels of ingrowth were observed in the intramedullary region of the implants when compared with the cortical region. Implant metal type did not affect ingrowth in both regions analyzed. Both fibrillar and crosslinked forms of dermal type I collagen did not significantly alter bone ingrowth.     

Preliminary studies on the effects of direct current on the bone/porous implant interfaces

The effect of small direct current (∼8μA) upon the tensile strength of the interfacial union between porous metal and polymer implants (100–200 μm diam pores) and bone was studied in the femur of dogs. The present results show that the electrical stimulation accelerates the rate of bony tissue growth into pores of the implants regardless of the nature of the materials tested. It is particularly exciting to find that the porous metal can be used as an electrode as well as an implant. This implies that an ordinary prosthesis made of metal can be made porous and the fixation time period can be shortened by the electrical stimulation. This has an enormous potential for all the direct fixation prostheses for rapid achievement of fixation.     

Use of tricalcium phosphate or electrical stimulation to enhance the bone-porous implant interface

Implant stabilization by biologic ingrowth into a porous surface offers a durable method of prosthetic fixation. These systems, however, lack the immediate stability offered by the use of acrylic bone cement. The interface strength of porous coated Co--Cr--Mo in a canine model does not approach that of acrylic bone cement until two weeks postoperatively. It is expected that this would be a minimum time period in clinical applications. Both chemical and electrical means have been advocated as methods to affect tissue ingrowth. A study using a canine model was undertaken to determine tissue ingrowth rates utilizing examples of these two methods: (1) impregnation of the porous structures with tricalcium phosphate powder (TCP); or (2) the application of an electrical stimulator to the implant with the implant itself serving as the cathode. Ten implants were coated with TCP, two each at weekly intervals from 1 to 5 weeks. Plain porous rods were likewise implanted, serving as the controls. While histology did reveal a slightly more dense bony structure, the interface bond strength was not affected by TCP. Electrical stimulation of the implant was similarly investigated with an additional time period of 10 weeks. Compared to the controls, the electrically stimulated implants reveal no statistically demonstratable difference in interface strength. Histologic specimens indicate larger areas of calcification than are observed in the controls.     

A percutaneous implant using a porous metal surface coating for adhesion to bone and a velour covering for soft tissue attachment: results of trials in pigs.

A percutaneous implant for the attachment of an artificial limb has been designed and tested in 14 pigs. Firm fixation to bone was achieved with the porous-surface layered metal intramedullary stem design in some cases. Dacron velour was used at the soft tissue interface. Evidence of soft tissue ingrowth was seen. However, the velour was unable to maintain adequate epithelial adhesion to form an anatomical seal and a barrier to bacteria.     

Processing and biocompatibility evaluation of laser processed porous titanium

The Laser Engineered Net Shaping (LENS™) method was used to fabricate porous Ti implants. Porous Ti structures with controlled porosity in the range of 17–58 vol.% and pore size up to 800 μm were produced by controlling LENS™ parameters, which showed a broad range of mechanical strength of 24–463 MPa and a low Young’s modulus of 2.6–44 GPa. The effects of porous structure on bone cell responses were evaluated in vitro with human osteoblast cells (OPC1). The results showed that cells spread well on the surface of porous Ti and formed strong local adhesion. MTT assay indicated LENS™ processed porous Ti provides a preferential surface for bone cell proliferation. Porous Ti samples also stimulated faster OPC1 cell differentiation compared with polished Ti sheet, which could be due to the change in cell morphology within the pores of Ti samples. More extracellular matrix and a higher level of alkaline phosphatase expression were found on the porous samples than on the Ti sheet. This can be beneficial for faster integration of porous implant with host bone tissue. The results obtained also indicated that a critical pore size of 200 μm or higher is needed for cell ingrowth into the pores, below which OPC1 cells bridged the pore surface without any growth in the pores.     

Characteristics of hydroxyapatite coated titanium porous coatings on Ti-6Al-4V substrates by plasma sprayed method

A porous metal coating applied to solid substrate implants has been shown, in vivo, to anchor implants by bone ingrowth. Calcium phosphate ceramics, in particular hydroxyapatite [Ca(10)(PO(4))(6)(OH)(2), HA], are bioactive ceramics, which are known to be biocompatible and osteoconductive, and these ceramics deposited on to porous-coated devices may enhance bone ingrowth and implant fixation. In this study, bi-feedstock of the titanium powder and composite (Na(2)CO(3)/HA) powder were simultaneously deposited on a Ti-6Al-4V substrate by a plasma sprayed method. At high temperature of plasma torch, the solid state of Na(2)CO(3) would decompose to release CO(2) gas and then eject the molten Ti powder to induce the interconnected pores in the coatings. After cleaning and soaking in deionized water, the residual Na(2)CO(3) in the coating would dissolve to form the open pores, and the HA would exist at the surface of pores in the inner coatings. By varying the particle size of the composite powder, the porosity of porous coating could be varied from 25.0 to 34.0%, and the average pore size of the porous coating could be varied to range between 158.5 and 202.0 microm. Using a standard adhesive test (ASTM C-633), the bonding strength of the coating is between 27.3 and 38.2 MPa. By SEM, the HA was observed at the surface of inner pore in the porous coating. These results suggest that the method exhibits the potential to manufacture the bioactive ceramics on to porous-coated specimen to achieve bone ingrowth fixation for biomedical applications.