An evaluation of bone growth into porous high density polyethylene.

The purpose of this investigation was to study bone growth into porous polyethylene rods as a function of time and pore structure. Previous studies have indicated the biocompatibility of solid polyethylene materials which are currently being used clinically. Porous polyethylene rods were implanted in the femurs of mongrel dogs which are sacrificed four, eight, and 16 weeks postoperatively. The implants were then sectioned and examined histologically and microadiographically. Quantitative techniques were employed to determine the amount of bone ingrowth as a function of time and pore size. The pore structures of the materials were evaluated using optical microscopy and mercury intrusion porosimetry. The results of this investigation have demonstrated that porous polyethylene is capable of accepting bone growth into pores as small as 40 mum. The optimum rate of bone ingrowth was observed in pore sizes of approximately 100 to 135 mum, with no increase in the rate of bone ingrowth observed in samples possessing larger pore sizes. No adverse tissue response was found at implant times up to 16 weeks in pore sizes of 100 mum or larger.     

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.     

Quantitative bone remodelling resulting from the use of porous dental implants

Histomorphometric analyses were used to quantitatively determine the patterns of bony ingrowth which resulted from the placement of porous-surfaced dental implants into the mandibles of Rhesus monkeys for up to 74 months utilizing a two-stage approach. Quantitative histopathologic evaluations were made using ground section microscopy. Implant stability resulting from bone remodelling and ingrowth occurred to varying degrees with all implants. Bone ingrowth occurred from medullary trabeculae and contact with the adjacent cortical plates. Quantitative histomorphometric analyses revealed that in only one case was the bone ingrowth into the available internal pores less than 45%. Minimal fibrous connective tissue ingrowth was observed in the implant crypts and was not thought to be due to micro-motion. The observed bone remodelling indicated a favorable prognosis for long-term implant performance.     

Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength.

The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability.     

Study of soft tissue ingrowth into canine porous coated femoral implants designed for osteosarcomas management

The objective of this project was to characterize soft tissue bonding to porous coated implants such as those that would be used for resection-reconstruction of osteosarcoma cases. We were interested in determining conditions which would provide both mechanical attachment of the implant to the surrounding tissue and produce a vascularized interface. In a bilateral canine implant model, both femoral mid-shafts were replaced with a porous coated cobalt-chrome segmental implant fabricated with average pore sizes of 300 microns or 900 microns. Twelve implants, six of each pore size, were used in six dogs. Two dogs were sacrificed at 2, 4, and 6 months after implantation. The soft tissue-implant interface was characterized mechanically with peel tests and histologically using light microscopy and immunohistochemistry. At all periods, a nonvascularized fibrous membrane surrounded the smaller pore size implants, without ingrowth or mechanical bonding. In contrast, a vascularized membrane developed within and around the larger pore size implants; the attachment strength increasing with implantation time. The vascularity increased in size and quantity with time. This study demonstrates the feasibility of obtaining vascularized soft tissue attachment to tumor replacement implants with appropriate porous coated implant design.     

Alkali- and heat-treated porous titanium for orthopedic implants

This study was carried out to investigate the effects of the alkali and heat treatments on the bone-bonding behavior of porous titanium implants. Porous titanium implants had a 4.6 mm solid core and a 0.7 mm thick porous outer layer using pure titanium plasma-spray technique. Three types of porous implants were prepared from these pieces: 1.control implant (CL implant) as manufactured 2.AW-glass ceramic bottom-coated implant (AW implant) in which AW-glass ceramic was coated on only the bottom of the pore of the implant 3.alkali- and heat-treated implant (AH implant), where implants were immersed in 5 mol/L NaOH solution at 60 degrees C for 24 h and subsequently heated at 600 degrees C for 1 h. The implants were inserted into bilateral femora of six dogs hemi-transcortically in a randomized manner. At 4 weeks, push-out tests revealed that the mean shear strengths of the CL, AW, and AH implants were about 10.8, 12.7, and 15.0 MPa, respectively. At 12 weeks there was no significant difference between the bonding strengths of the three types of the porous implants (16.0-16.7 MPa). Histologically and histomorphologically, direct bone contact with the implant surface was significantly higher in the AH implants than the CL and AW implants both at 4 and 12 weeks. Thus, the higher bonding strength between bone and alkali- and heat-treated titanium implants was attributed to the direct bonding between bone and titanium surface. In conclusion, alkali and heat treatments can provide porous titanium implants with earlier stable fixation.     

Bone growth in rapid prototyped porous titanium implants

Two porous titanium implants with a pore size diameter of 800 and 1200 microm (Ti800 and Ti1200) and an interconnected network were manufactured using rapid prototyping. Their dimensions and structure matched those of the computer assisted design. The porosity of the implants was around 60%. Their compressive strength and Young's modulus were around 80 MPa and 2.7 GPa, respectively. These values are comparable to those of cortical bone. The implants were implanted bilaterally in the femoral epiphysis of 15 New Zealand White rabbits. After 3 and 8 weeks, abundant bone formation was found inside the rapid prototyped porous titanium implants. For the Ti1200 implants, bone ingrowth was (23.9 +/- 3.5)% and (10.3 +/- 2.8)%, respectively. A significant statistical difference (p < 0.05) was found for bone ingrowth in the Ti1200 between the two delays. The percentage of bone directly apposited on titanium was (35.8 +/- 5.4)% and (30.5 +/- 5.0)%. No significant difference was found for bone-implant contact between the different time periods and pore sizes. This work demonstrates that manufacturing macroporous titanium implants with controlled shape and porosity using a rapid prototyping method is possible and that this technique is a good candidate for orthopedic and maxillofacial applications.     

Bone growth in biomimetic apatite coated porous Polyactive 1000PEGT70PBT30 implants

We recently, developed a simple one-day one-step incubation method to obtain bone-like apatite coating on flexible and biodegradable Polyactive 1000PEGT70PBT30. The present study reports a preliminary biological evaluation on the coated polymer after implantation in rabbit femurs. The porous cylindrical implants were produced from a block fabricated by injection molding and salt leaching. This technique provided the block necessary mechanical integrity to make small cylinders (diameter 3.5 x 5 mm2) that were suitable for implantation in rabbits. The coating continuously covered the surface of the polymer, preserving the porous architecture of outer contour of the cylinders. Two defects with a diameter of 3.5 or 4 mm were drilled in the proximal and distal part of femur diaphysis. The implants were inserted as press-fit or undersized into the cortex as well as in the marrow cavity. The polymer swelled after implantation due to hydration, leading to a tight contact with the surrounding bone in both defects. The adherence of the coating on the polymer proved to be sufficient to endure a steam sterilization process as well as the 15% swelling of the polymer in vivo. The coated Polyactive 1000PEGT70PBT30 has a good osteoconductive property, as manifested by abundant bone growth into marrow cavity along the implant surface during 4-week implantation. A favorable bioactive effect of the coating with an intimate bone contact and extensive bone bonding with this polymer was qualitatively confirmed. Concerning the bone ingrowth into the porous implant in the defect of 4 mm diameter, only marginal bone formation was observed up to 8 weeks with a maximal penetration depth of about 1 mm. The pore interconnectivity is important not only for producing a coating inside the porous structure but also for bone ingrowth into this biodegradable material. This preliminary study provided promising evidence for a further study using a bigger animal model.     

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.     

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.     

Tissue ingrowth of Replamineform implants.

The Replamineform process, a new technique for the fabrication of porous hard tissue implant materials which replicates the skeletal configuration of certain marine invertebrates, was used to manufacture 1 cm long by 0.5 cm diam cylinders. The inherent advantages of porous configurations obtained through this process are controlled, uniform pore size, controlled pore-microstructure ratio, and complete interconnection of pores. The specific materials studied were chrome-cobalt-molybdenum alloy, alphaA103, hydroxyapatite prepared by hydrothermal conversion, and the basic (aragonite) CaCO3 skeleton of the coral genus Porities. The implants were placed in the canellous bone of the distal femora and proximal tibiae of adult, mongrel dogs and analyzed at 8 weeks for tissue response and ingrowth. Uniformly, new bone was found to grow into the pores of these materials and become normally mineralized. These findings were determined by microradiography, scanning electron microscopy, electron microprobe analysis, and histology. No evidences of infection, rejection, or encapsulation were seen. In the case of those CaCO3 implants left in place for 1 year, there was almost complete resorption of the cylinders, with both bony trabeculae and unmineralized collagen (presumably osteoid) found at the sites of insertion.     

Effect of nitinol implant porosity on cranial bone ingrowth and apposition after 6 weeks.

The present study addresses two aspects of the use of nitinol in cranial bone defect repair. The first is to verify that there is substantial bone ingrowth into the implant after 6 weeks; the second is to determine the effect of pore size on the ability of bone to grow into the implant during the early (6-week) postoperative period. Porous equiatomic (equal atomic masses of titanium and nickel) nickel-titanium (nitinol) implants with three different morphologies (differing in pore size and percent porosity) were implanted for 6 weeks in the parietal bones of New Zealand White rabbits. Ingrowth of bone into the implants and apposition of bone along the exterior and interior implant surfaces were calculated. The mean pore size (MPS) of implant type #1 (353 +/- 74 microm) differed considerably from implant types #2 (218 +/- 28 microm) and #3 (178 +/- 31 microm). There was no significant difference among implant types in the percentages of bone and void/soft tissue composition of the aggregate implants. The amount of bone ingrowth also was not significantly different among the implant types. Implant #1 was significantly higher in pore volume and thus had a significantly higher volume of ingrown bone (2.59 +/- 0.60 mm3) than implant #3 (1. 52 +/- 0.66 mm3) and a greater amount, but not significantly greater, than implant #2 (1.76 +/- 0.47 mm3). Pore size does not appear to affect bone ingrowth during the cartilaginous period of bone growth in the implant. This implies that within the commonly accepted range of implant porosities (150-400 microm), at 6 weeks bone ingrowth near the interface of nitinol implants is similar.     

The effect of surface modification of a porous TiO2/perlite composite on the ingrowth of bone tissue in vivo

The porous TiO2/perlite composite Ecopore is a synthetic biomaterial with possible clinical application in bone substitution. In our previous work, we demonstrated that surface modification of Ecopore with fibronectin (FN) enhanced spreading and growth of human osteoblasts in vitro. In the present study, we implanted untreated, alkaline-etched and FN-coated Ecopore cylinders into critical size defects of rabbit femora and applied pulsed polychrome sequence staining. After 6 weeks, sections of the implants were investigated via conventional and fluorescence microscopy. A partial ingrowth of bone matrix into the pore system of the Ecopore implants was observed. At the contact zones, the bone appeared to be directly connected to the implant without detectable gaps. Defect healing was complete within 6 weeks, while fibrous tissue generation or inflammation were absent in the implant modification groups, demonstrating basic Ecopore biocompatibility. The mean bone apposition rates within the implant cross-section were 4.1+/-0.6 microm/day (p<0.001) in the FN-coated group and 3.3+/-0.5 microm/day (p<0.05) in the NaOH-etched group. In both treated Ecopore modification groups, the apposition rates were significantly higher than in the non-modified control (2.9+/-0.6 microm/day), indicating bone growth stimulation by pre-treatment. Energy-dispersive X-ray analysis confirmed that significantly more bone tissue was formed inside the pores of the FN-coated implants compared to the unmodified control. The cross-sectional areas identified as ingrown bone amounted to 18.5+/-6.1% (p<0.05) in the FN group, 13.4+/-5.1% (p>0.05) in the NaOH-etched group and 10.2+/-5.5% in the unmodified group. In summary, we conclude that bone tissue tolerates Ecopore well and that tissue ingrowth can be enhanced by etching and coating with FN.     

Characteristics of tissue growth into Proplast and porous polyethylene implants in bone.

(1) Bone does not form within internal pores of undistorted Proplast implants because of the small interconnecting pore size of the material; (2) the nonosseous, fibrous tissue which exists in the pores of Proplast implants in bone is not attached to the surrounding bone (i.e., Sharpey's fibers are not present). The load-bearing support which can be afforded by Proplast implants is limited by the incomplete bone ingrowth along the margins of the material and the tensile strength of Proplast.     

Osteoconduction at porous hydroxyapatite with various pore configurations

To assess the histological response and the reinforcing effects of bone ingrowth within porous hydroxyapatite (HA) implants depending on pore geometry, four kinds of cylindrical-type with parallel linear pores phi50, 100, 300, 500 microm), one kind of sponge-type with irregular interconnecting pores (phi250 microm) and one cross-type with crossing linear pores (phi100 x 120 microm) of porous HA were prepared. Eighty-four rabbits were divided into six groups, and a 5 x 5 x 7 mm sized porous HA block was inserted through the medial cortical window of the proximal tibia. Histomorphological changes were examined using light and scanning electron microscopy. A biomechanical compression test was performed using material test machines. After implantation, the implants showed different histological changes depending on pore geometry. Active osteoconduction was also found in the phi50 microm sized cylindrical-type porous HA. Evidence of remodeling of new bone and bone marrow formation within porous HA was found in the larger cylindrical-types (phi300, 500 microm), and the sponge- and cross-types. The biomechanical test showed that the ultimate compressive strength increased significantly in the phi300 microm sized cylindrical-type, and in the sponge- and cross-types eight weeks after implantation. Porous HA with cylindrical pores could be a useful graft material due to its strength, osteoconductivity and the ease with which its pore geometry can be controlled.     

In vivo bone response to porous calcium phosphate cement

We conducted an in vivo experiment to evaluate the resorption rate of a calcium phosphate cement (CPC) with macropores larger than 100 microm, using the CPC called Biocement D (Merck Biomaterial, Darmstadt, Germany), which after setting only shows pores smaller than 1 microm. The gas bubble method used during the setting process created macroporosity. Preset nonporous and porous cement implants were inserted into the trabecular bone of the tibial metaphysis of goats. The size of the preset implants was 6 mm and the diameter of the drill hole was 6.3 mm, leaving a gap of 0.3 mm between implant surface and drill wall. After 2 and 10 weeks, the animals were euthanized and cement implants with surrounding bone were retrieved for histologic evaluation. Light microscopy at 2 weeks revealed that the nonporous implants were surrounded by connective tissue. On the cement surface, we observed a monolayer of multinucleated cells. Ten weeks after implantation, the nonporous implants were still surrounded by connective tissue. However, a thin layer of bone now covered the implant surface. No sign of cement resorption was observed. In contrast, the porous cement evoked a completely different bone response. At 2 weeks, bone formation had already occurred inside the implant porosity. Bone formation even appeared to occur as a result of osteoinduction. Also, at their outer surface, the porous implants were completely surrounded by bone. At 2 weeks, about 31% of the initial cement was resorbed. After 10 weeks, 81% of the initial phosphate cement was resorbed and new bone was deposited. On the basis of these observations, we conclude that the creation of macropores can significantly improve the resorption rate of CPC. This increased degradation is associated with almost complete bone replacement.     

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.     

The effect of sol-gel-formed calcium phosphate coatings on bone ingrowth and osteoconductivity of porous-surfaced Ti alloy implants

Ti-6Al-4V implants formed with a sintered porous surface for implant fixation by bone ingrowth were prepared with or without the addition of a thin surface layer of calcium phosphate (Ca-P) formed using a sol-gel coating technique over the porous surface. The implants were placed transversely across the tibiae of 17 rabbits. Implanted sites were allowed to heal for 2 weeks, after which specimens were retrieved for morphometric assessment using backscattered scanning electron microscopy and quantitative image analysis. Bone formation along the porous-structured implant surface, was measured in relation to the medial and lateral cortices as an indication of implant surface osteoconductivity. The Absolute Contact Length measurements of endosteal bone growth along the porous-surfaced zone were greater with the Ca-P-coated implants compared to the non-Ca-P-coated implants. The Ca-P-coated implants also displayed a trend towards a significant increase in the area of bone ingrowth (Bone Ingrowth Fraction). Finally, there was significantly greater bone-to-implant contact within the sinter neck regions of the Ca-P-coated implants.     

Enhancement of bone regeneration using resorbable ceramics and a polymer-ceramic composite material

The aim of this experimental study was to evaluate the use of resorbable implants for the repair of nonloaded skeletal defects. Porous ceramic implants of alpha-TCP, of glass-ceramic, and of solid composite implants of glass-ceramic/polylactic acid 8 mm in diameter and 2 mm in thickness were fabricated and implanted pressfit into biparietal, full-thickness defects of the calvaria of 60 adult rats. Twenty rats received unfilled defects and served as controls. Fluorochrome labeling of bone formation was performed during the observation period. Five animals from each group were evaluated after 6, 13, 26, and 52 weeks. The control defects showed incomplete regeneration, with bone formation extending 1.66 mm, on average, into the defect after 52 weeks. In the group of alpha-TCP implants, histologic evaluation indicated that the bone formed during initial stages had undergone resorption later on, so that bone repair after 52 weeks was not significantly enhanced, with an average depth of 1.83 mm of bone ingrowth. The glass-ceramic implants exhibited extensive bone formation and nearly complete repair of the calvarial defect, with 3.90 mm of bone ingrowth into the implant pores. Degradation of the ceramic was nearly complete, with a few remaining particles surrounded by soft tissue. The composite implants showed a negligible bone ingrowth of 0.63 mm, on average. Soft tissue had invaded the polylactic acid implant body, but no bone formation had taken place at the surface of the embedded ceramic particles. Degradation of the polymer was not complete after 52 weeks. It is concluded that the balance between degradation and bone formation is delicate and that chemical events and cellular reaction during degradation may counteract complementary bone ingrowth.