Effect of porosity on the osteointegration and bone ingrowth of a weight-bearing nickel-titanium bone graft substitute

Porous nickel-titanium (NiTi) alloy is a promising new material for a bone graft substitute with good strength properties and an elastic modulus closer to that of bone than any other metallic material. The purpose of this study was to evaluate the effect of porosity on the osteointegration of NiTi implants in rat bone. The porosities (average void volume) and the mean pore size (MPS) were 66.1% and 259+/-30 microm (group 1, n=14), 59.2% and 272+/-17 microm (group 2, n=4) and 46.6% and 505+/-136 microm (group 3, n=15), respectively. The implants were implanted in the distal femoral metaphysis of the rats for 30 weeks. The proportional bone-implant contact was best in group 1 (51%) without a significant difference compared to group 3 (39%). Group 2 had lower contact values (29%) than group 1 (p=0.038). Fibrotic tissue within the porous implant was found more often in group 1 than in group 3 (p=0.021), in which 12 samples out of 15 showed no signs of fibrosis. In conclusion, porosity of 66.1% (MPS 259+/-30 microm) showed best bone contact (51%) of the porosities tested here. However, the porosity of 46.6% (MPS 505+/-136 microm) with bone contact of 39% was not significantly inferior in this respect and showed lower incidence of fibrosis within the porous implant.     

Effects of bone ingrowth on the strength and non-invasive assessment of a coralline hydroxyapatite material

The dependence of strength on the amount of bone growth into a hydroxyapatite material made from coral was investigated. Block and granular forms of the material were implanted into cortical and trabecular regions of the skeletons of 16 dogs. The results were examined after 4, 8, 12 and 16 wk, with four dogs in each experimental group. When implanted into cortical bone, the bending strength of the implant material was found to be highly correlated with the amount of pore space which had become occupied by bone (r = 0.92, P less than 0.005 for the block form; r = 0.84, P less than 0.005 for the granular form). Multiple regression analysis showed that six histomorphometric measures of ingrowth accounted for 96% of the variability in bending strength of the block material, and there were no significant differences between block and granular forms of the material. On the other hand, when implanted into trabecular bone, the block form of the material achieved greater compressive strength than the granular form. While both strength and ingrowth increased with time, there were poor correlations between these two variables. Finally, when the material is implanted into trabecular bone, it becomes stronger in compression than the surrounding bone; when implanted in cortical bone, linear modelling suggests that resorption and replacement of the implant would be required to approximate the bending strength of the surrounding bone.     

Development of a large titanium bone chamber to study in vivo bone ingrowth

In the bone conduction chamber (BCC) various materials and factors have been tested for their effect on bone graft incorporation and bone healing. However, biomaterials often have to be crushed to fit in this small chamber. Since cellular responses to biomaterials are influenced by the size and shape of particles, research concerning the evaluation of biomaterials is limited by the dimensions of this bone chamber. We enlarged and modified the BCC in order to be able to investigate the in vivo influences of biomaterials, growth factors and bone graft processing on tissue and bone ingrowth. Seven goats received four bone chambers each, three modified models and a BCC. The first model (BCC+) had two ingrowth openings, similar to that of the BCC. The second model had two round ingrowth openings (ROU). The third model had a open bottom for bone ingrowth (BOT). After 12 weeks, bone ingrowth distances were measured on histological sections and using muCT. Bone ingrowth was significantly higher (p=0.009 and 0.008) in the ROU compared to the BCC+ and the BOT, respectively. Similar results were found using muCT. The ROU model performed most similar to the BCC (gold standard) and is considered to be a promising new tool in biomaterials research.     

Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes

Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced (23-47% and 32-42% for batches A and B, respectively). These observations suggest that differences in the volume of bone ingrowth initially depended on pore interconnectivity rather than pore size, whereas the volume or morphology of the PHA influenced the volume and morphology of bone ingrowth at later time points. Compression testing showed that bone ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a strong correlation was identified between mechanical properties and the absolute volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks, there was no significant variation in the ultimate compressive strength of integrated batch A and B implants. This similarity in ultimate mechanical properties indicated that the absolute volume of ingrowth may be mediated by the PHA structure through its impact on the dynamics of the local biomechanical environment. The results of push-out testing showed that fixation of PHA bone graft substitutes was independent of density within the range studied, with no significant difference in the interfacial shear stress between batches A and B at each time point throughout the study.     

Temporal effects of a COX-2-selective NSAID on bone ingrowth

The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.     

Calcium-deficient apatite: a first in vivo study concerning bone ingrowth

Biphasic calcium phosphate (BCP) materials are increasingly used to restore bone loss in surgery. Calcium-deficient apatites (CDA), the precursors of BCP, are closer in structure to biological apatites and can be associated with therapeutic agents to form drug-delivery systems. The purpose of this first in vivo study of CDA was to evaluate the osteoconductive properties of two composites, consisting of 40-80 microm granules carried by a cellulose-derived polymer, used to fill critical size bone defects in rabbit femoral ends. Animals were sacrificed 2 or 3 weeks after implantation. Histomorphometric analysis of scanning electron microscopy implant surface files was performed using gray level threshold that distinguish between bone or materials (white) and noncalcified tissue (black). Quantitative results for new bone formation showed no significant differences between the composites or the implantation periods. However, nearly all of the CDA disappeared early while supporting more extensive bone colonization than biphasic calcium phosphates implanted in the same conditions.     

Biomimetic nano-apatite coating capable of promoting bone ingrowth

Nano-apatite coating closely mimicking bone mineral was grown directly on titanium soaked in an aqueous solution containing all major inorganic components present in the body, mainly, HCO3(-), Ca(2+), HPO4(2-), and Mg(2+) ions. The removal of HCO3(-) ions from the solution in the form of CO2 resulted in the increase of solution pH. As a consequence of this reaction, the nano-apatite coating was formed on the surface of titanium with composition and structure equivalent to those of bone mineral. The biomimetic nano-apatite was demonstrated to be capable of conducting bone formation and promoting direct bone apposition. This bioactive coating also affected the behavior of human osteoblasts as indicated by their morphologies observed in cell culture study.     

In vitro corrosion study of porous metal fibre coatings for bone ingrowth

As a first part of a biocompatibility testing programme, in vitro corrosion tests were carried out on porous stainless steel AISI 316L and titanium compacts made of 100 microns thick fibres. The present porous metal structures are used as coatings on permanent orthopaedic implants; with osseous tissue invading the pores, the implant becomes securely anchored to the surrounding bone. The results show that no inadvertent reactions occur with porous titanium. It can probably be used with no greater risk of localized electrochemical attack than the parent bulk material.     

Improved bone ingrowth and fixation with a thin calcium phosphate coating intended for complete resorption

Bonit is claimed to be a resorbable electrochemically deposited calcium phosphate coating consisting mainly of brushite, which is a hydroxyapatite precursor. This study involved a comparison of Ti6Al4V screw-shaped implants with and without a 15 +/- 5 microm Bonit coating in rabbit tibia and femur, after 6 and 12 weeks of insertion. The biomechanical removal torque test showed significantly increased values for the coated implants after 12 weeks (p < 0.05) but not after 6 weeks of integration. Higher bone-implant contact was found for the coated implants in the tibia after 6 weeks and for both tibial and femoral screws after 12 weeks (p < 0.05). There was no difference in the inflammatory reaction around the implants, and possible grains of the coating could be detected after 6 weeks, but not after 12 weeks of follow-up. This unloaded short-term study has shown promising results for the easily applicable and resorbable coat (Bonit) compared to uncoated titanium-alloy 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.     

The rate of bone ingrowth into porous metal.

Experiments have been devised to study the rate of ingrowth of bone into porous metal with pore sizes up to 100 mu and to study the significance of a gap between the porous metal surface and bone. When the porous coat was in direct apposition with bone, the implant was firmly locked in place after a three week period and the plateau value of implant-tissue shear strength was reached at four weeks. A gap of 1.5 mm between the bone and the implant was bridged by new bone within four weeks.     

Ontogenetic structural and material variations in ovine calcanei: A model for interpreting bone adaptation

Experimental models are needed for resolving relative influences of genetic, epigenetic, and nonheritable functionally induced (extragenetic) factors in the emergence of developmental adaptations in limb bones of larger mammals. We examined regional/ontogenetic morphologic variations in sheep calcanei, which exhibit marked heterogeneity in structural and material organization by skeletal maturity. Cross‐sections and lateral radiographs of an ontogenetic series of domesticated sheep calcanei (fetal to adult) were examined for variations in biomechanically important structural (cortical thickness and trabecular architecture) and material (percent ash and predominant collagen fiber orientation) characteristics. Results showed delayed development of variations in cortical thickness and collagen fiber orientation, which correlate with extragenetic factors, including compression/tension strains of habitual bending in respective dorsal/plantar cortices and load‐related thresholds for modeling/remodeling activities. In contrast, the appearance of trabecular arches in utero suggests strong genetic/epigenetic influences. These stark spatial/temporal variations in sheep calcanei provide a compelling model for investigating causal mechanisms that mediate this construction. In view of these findings, it is also suggested that the conventional distinction between genetic and epigenetic factors in limb bone development be expanded into three categories: genetic, epigenetic, and extragenetic factors. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc.     

Assessment of bone ingrowth into porous biomaterials using MICRO-CT

The three-dimensional (3D) structure and architecture of biomaterial scaffolds play a critical role in bone formation as they affect the functionality of the tissue-engineered constructs. Assessment techniques for scaffold design and their efficacy in bone ingrowth studies require an ability to accurately quantify the 3D structure of the scaffold and an ability to visualize the bone regenerative processes within the scaffold structure. In this paper, a 3D micro-CT imaging and analysis study of bone ingrowth into tissue-engineered scaffold materials is described. Seven specimens are studied in this paper; a set of three specimens with a cellular structure, varying pore size and implant material, and a set of four scaffolds with two different scaffold designs investigated at early (4 weeks) and late (12 weeks) explantation times. The difficulty in accurately phase separating the multiple phases within a scaffold undergoing bone regeneration is first highlighted. A sophisticated three-phase segmentation approach is implemented to develop high-quality phase separation with minimal artifacts. A number of structural characteristics and bone ingrowth characteristics of the scaffolds are quantitatively measured on the phase separated images. Porosity, pore size distributions, pore constriction sizes, and pore topology are measured on the original pore phase of the scaffold volumes. The distribution of bone ingrowth into the scaffold pore volume is also measured. For early explanted specimens we observe that bone ingrowth occurs primarily at the periphery of the scaffold with a constant decrease in bone mineralization into the scaffold volume. Pore size distributions defined by both the local pore geometry and by the largest accessible pore show distinctly different behavior. The accessible pore size is strongly correlated to bone ingrowth. In the specimens studied a strong enhancement of bone ingrowth is observed for pore diameters>100 microm. Little difference in bone ingrowth is measured with different scaffold design. This result illustrates the benefits of microtomography for analyzing the 3D structure of scaffolds and the resultant bone ingrowth.     

Calvaria bone chamber--a new model for intravital assessment of osseous angiogenesis

The faith of tissue engineered bone replacing constructs depends on their early supply with oxygen and nutrients, and thus on a rapid vascularization. Although some models for direct observation of angiogenesis are described, none of them allows the observation of new vessel formation in desmal bone. Therefore, we developed a new chamber model suitable for quantitative in vivo assessment of the vascularization of bone substitutes by intravital fluorescence microscopy. In the parietal calvaria of 32 balb/c mice a critical size defect was set. Porous 3D-poly(L-lactide-co-glycolide) (PLGA)-blocks were inserted into 16 osseous defects (groups 3 and 4) while other 16 osseous defects remained unequipped (groups 1 and 2). By placing a polyethylene membrane onto the dura mater, the angiogenesis was mainly restricted to the osseous margins (groups 2 and 4). Microvascular density, angiogenesis, and microcirculatory parameters were evaluated repetitively during 22 days. In all animals, only a mild inflammatory reaction was observed with a climax after 2 weeks. The implantation of PLGA scaffolds resulted in a vascular growth directed towards the center of the defect as demonstrated by the significantly (p < 0.05) enhanced central microvascular densitiy from day 3 to day 22 when compared with unequipped chambers. The additional application of polyethylene membrane was found to reduce significantly the microvessel density mainly in the center of both scaffolds and defects. The present calvaria bone chamber allows for the first time to assess quantitatively the angiogenesis arising from desmal bone directly in vivo. Therefore, this chronic model may support the future research in the biological adequacy of bone substitutes.     

Use of stereolithography to manufacture critical-sized 3D biodegradable scaffolds for bone ingrowth

A novel approach to the manufacture of biodegradable polymeric scaffolds for tissue-engineering utilizing stereolithography (SLA) is presented. SLA is a three-dimensional (3D) printing method that uses an ultraviolet laser to photo-crosslink a liquid polymer substrate. The current generation of SLA devices provide a 3D printing resolution of 0.1 mm. The experiments utilized a biodegradable resin mixture of diethyl fumarate (DEF), poly(propylene fumarate) (PPF), and a photoinitiator, bisacylphosphine oxide (BAPO). The PPF is crosslinked with the use of the SLA's UV laser (325-nm wavelength). An SLA device was retrofitted with a custom fixture build tank enclosing an elevator-driven build table. A 3D prototype model testing the manufacturing control this device provides was created in a computer-aided-design package. The resulting geometric data were used to drive the SLA process, and a DEF/PPF prototype part was successfully manufactured. These scaffolds have application in the tissue engineering of bony substrates.     

Balancing incompatible endoprosthetic design goals: a combined ingrowth and bone remodeling simulation

In order to design a good cementless femoral implant many requirements need to be fulfilled. For instance, the range of micromotions at the bone-implant interface should not exceed a certain threshold and a good ratio between implant-bone stiffness that does not cause bone resorption, needs to be ensured. Stiff implants are known to evoke lower interface micromotions but at the same time they may cause extensive resorption of the surrounding bone. Composite stems with reduced stiffness give good remodeling results but implant flexibility is likely to evoke high micromotions proximally. Finding a good balance between these incompatible design goals is very challenging. The current study proposes a finite element methodology that employs subsequent ingrowth and remodeling simulations and can be of assistance when designing new implants. The results of our simulations for the Epoch stem were in a good agreement with the clinical data. The proposed implant design made of porous tantalum with an inner CoCrMo core performed slightly better with respect to the Epoch stem and considerably better with respect to a Ti alloy stem. Our combined ingrowth and remodeling simulation can be a useful tool when designing a new implant that well balances mentioned incompatible design goals.     

3D打印钛合金孔隙支架骨长入影响因素的分析

BACKGROUND: With the development of three-dimensional (3D) printing technology, 3D printed porous titanium scaffolds as bone substitutes have become a research hotspot. OBJECTIVE: To introduce and discuss the effects of each parameter of 3D printed porous titanium scaffolds on bone ingrowth, and to sum out the optimal parameters for bone ingrowth. METHODS: The first author retrieved PubMed, Springerlink and Medline databases with “three-dimensional (3D) printing, scaffold, titanium, bone ingrowth” as keywords for relevant articles published from 2006 to 2016. 125 articles were retrieved initially, and finally 42 eligible articles were included for analysis. RESULTS AND CONCLUSION: Pore size, porosity, pore structures and surface modifications of 3D printed porous titanium scaffolds all make effects on bone ingrowth or osteoblasts in scaffolds. Scaffolds with appropriate pore size and porosity can promote the vascularization and provide adequate nutrition and oxygen supplement, to ensure high cell viability. Regulations of cell performances, such as cell attachment, proliferation and differentiation, are also affected by pore structures and nano-scale surface modification. Herein, a detailed combination of the parameters, as mentioned above, can create a better porous scaffold for better bone ingrowth. Hence, the high-stability interface between bone and scaffolds may be obtained through the parameter adjustment.     

Effects of periosteal activation agent on bone repair and ingrowth

A substance that activates the resting periosteum (PAA) was applied to the periosteal surface in two different healing models using the femurs of 2-kg male rabbits. The activation agent was applied to the periosteal surface over the sites of circular defects drilled through the lateral cortex in one model and over the sites of porous polyethylene implants placed in the lateral cortex and the medullary canal in the other model. Results failed to show that the agent either enhanced bone ingrowth into the porous implants or accelerated bony filling of the circular defects. However, there was indication of enhanced mineralization and periosteal callus formation as early as 24 h after application.     

An ovine model to evaluate the biologic properties of impacted morselized bone graft substitutes

The objectives of this study were to develop and evaluate a bone-defect model to study the biologic behavior of biomaterials being considered for impaction grafting in revision hip arthroplasty. A miniature impactor was designed to produce pellets of aggregates at a standard compactive effort. In Phase 1, 22 sheep underwent implantation of pellets into six metaphyseal defects in both rear limbs. In Phase 2, eight sheep underwent surgical implantation of four pellets in metaphyseal defects. Defects were sealed with polymethylmethacrylate in both phases. Healing of the defects was evaluated at 7 weeks (Phase 1, n = 11) and 14 weeks (n =19) with computed tomography, histology, and histomorphometry. Complications in Phase 1 included four femoral fractures and migration of cement seals (18/102 defects). No complications occurred in Phase 2. Whereas no difference was found between left and right limbs, osteogenesis and incorporation of biomaterials varied among implantation sites. For comparison of grafting materials, treatment site allocations were randomized according to a Latin square design. This model allows evaluation of several impacted aggregates (including large particles) in the same animal. It is particularly suitable for analyzing the biologic properties of grafting materials prior to evaluation under loading conditions.     

Effect of weight-bearing on bone-bonding behavior of strontium-containing hydroxyapatite bone cement

The purpose of this study was to investigate and compare the chemical composition and nanomechanical properties at the bone-cement interface under non-weight-bearing and weight-bearing conditions, in order to understand the effect of weight-bearing on the bone-bonding behavior of strontium-containing hydroxyapatite (Sr-HA) cement. In one group, Sr-HA cement was injected into rabbit ilium (under non-weight-bearing conditions). Unilateral hip replacement was performed with Sr-HA cement (under weight-bearing conditions) in the other group. Six months later, scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) analysis and nanoindentation tests were conducted on the interfaces between cancellous bone and the Sr-HA cement. The nanoindentation results revealed two different transitional behaviors under different conditions. nder weight-bearing conditions, both the Young modulus and hardness at the interface were considerably higher than those at either the Sr-HA cement or cancellous bone. On the contrary, under non-weight-bearing conditions, both the Young modulus and hardness values at the interface were lower than those at the cancellous bone, but were higher than the Sr-HA cement. In addition, EDX results showed that the calcium and phosphorus contents at the interface under weight-bearing conditions were considerably higher than those under non-weight-bearing conditions. The differences in chemical composition and nanomechanical properties at the cement-bone interface under two different conditions indicate that weight-bearing produces significant effects on the bone-bonding behavior of the Sr-HA cement.