Similarity of bone ingrowth in rats and goats: a bone chamber study

Bone ingrowth has been studied extensively in rats by use of bone chambers. However, it is not known whether results in small animals, with respect to bone ingrowth processes, are similar in large animals, in which more realistic models are often used. Since the metabolic rate in small animals is, in general, higher than that in larger species, we hypothesized that bone ingrowth in chambers develops more rapidly in small animals. Therefore, identical bone chambers were placed in the tibias of rats and goats. After 6 and 12 weeks, histologic and histomorphometric examinations were carried out to measure bone and tissue ingrowth distances. Bone ingrowth was higher in both species at 12, compared with 6 weeks (P < 0.01). Tissue ingrowth in general (including soft tissue) was less in rats than in goats at both time periods (P < 0.001). However, bone ingrowth did not differ between species. Thus, when differences in size of an osseous defect are corrected for, there seems to be only little influence of differences in body size.     

Epiphyseal-based designs for tibial plateau components--I. Stress analysis in the frontal plane

Two-dimensional, finite element studies were conducted of the proximal tibia before and after joint arthroplasty. Equivalent-thickness models projected onto the mid-frontal plane were created for the natural, proximal tibia and for the proximal tibia with four different types of tibial plateau components. All components simulated bony ingrowth fixation, i.e. no cement layer existed between component and bone. In addition, the interface between component and bone was assumed to be intimately connected, representing complete bony ingrowth and a rigid state of fixation. Loads consisted of bi-condylar and uni-condylar forces. Results indicated that conventional plateau designs with central posts or multiple pegs led to higher stress magnitudes in the trabecular bone near the distal ends of the post/pegs and stress shielding at more proximal locations. A design without posts or pegs whose interface geometry mimics the epiphyseal plate minimizes bone stress shielding. An implant consisting of separate components covering each condyle was found effective in limiting component tilting and the consequent tensile stresses caused by non-symmetrical, uni-condylar loading.     

Composites for bone replacement

The application of synthetic materials for bone replacement is now well established, but it is recognized that mechanical compatibility, as well as biocompatibility, of the tissue and implant is required if stress shielding and consequent bone resorption is to be avoided at areas of fixation. The development of materials analogous to the natural tissue for longer term implantation is discussed, with particular reference to hydroxyapatite reinforced polymers.     

Drug test chamber: a titanium implant for administration of biochemical agents to a standardized bone callus in situ

A titanium implant in which a conduit is gradually filled with ingrowing bone (the Bone Harvest Chamber) has been modified to allow continuous local treatment of the conduit tissue with biochemical agents. Implants were inserted bilaterally in rabbit tibiae. The tissue content of the bone ingrowth conduits was studied with histology, ^99mTc-MDP scintimetry and measurements of total calcium content. Bone was formed in the conduit by endochondral formation starting at both ends and continuing until fusion in the middle. After 2 weeks the bone had not yet met in the middle where fibrous tissue was seen. In eight animals ³H-proline was applied via one of the chambers, with the contralateral chamber as a saline-treated control. The collagen of the harvested tissue from the ³H-proline treated side had a ³H-hydroxyproline content 1000 times greater than had the control side. The ‘drug test chamber’ makes possible the study of local effects of drugs on healing of mature bone in vivo.     

Porous hydroxyapatite as a bone graft substitute in cranial reconstruction: a histometric study

To assess the potential of a porous hydroxyapatite matrix to serve as a bone graft substitute, bilateral 15 X 20 mm craniectomy defects were reconstructed in 17 dogs with blocks of implant and split-rib autografts. Specimens were retrieved at 3, 6, 12, 24, and 48 months, and undecalcified sections were prepared for microscopy and histometry. The implant and graft cross-sectional areas did not change with time, documenting their equivalent ability to maintain cranial contour. Bone ingrowth extended across the implant from one cranial shelf to the other in 15 specimens. Little apparent bone ingrowth was seen in most graft specimens. Two implants and three grafts were nonunited, possibly due to lack of fixation or the orientation of the histology sections. The implant specimens were composed of 39.3 percent hydroxyapatite matrix, 17.2 percent bone ingrowth, and 43.5 percent soft-tissue ingrowth. The graft specimens were composed of 43.7 percent bone and 56.3 percent soft tissue. This study supported the thesis that a porous hydroxyapatite matrix may function in part as a bone graft substitute. The brittle hydroxyapatite matrix undoubtedly became stronger with bone ingrowth, but the degree of cranial protection achieved was not measured in this study. The size of the cranial defect used in this study did not permit estimation of the distance over which bone ingrowth may be reliably expected. There remains a need for greater understanding of the causes of nonunion, the extent of predictable ingrowth depth, and the strength of the resultant implant-bone composite.     

Bone ingrowth into a porous coated implant predicted by a mechano-regulatory tissue differentiation algorithm

Bone ingrowth into a porous surface is one of the primary methods for fixation of orthopaedic implants. Improved understanding of bone formation and fixation of these devices should improve their performance and longevity. In this study predictions of bone ingrowth into an implant porous coating were investigated using mechano-reculatory models. The mechano-regulatory tissue differentiation algorithm proposed by Lacroix et al., and a modified version that enforces a tissue differentiation pathway by transitioning from differentiation to bone adaptation were investigated. The modified algorithm resulted in nearly the same behavior as the original algorithm when applied to a fracture-healing model. The algorithms were further compared using micromechanical finite element model of a beaded porous scaffold. Predictions of bone and fibrous tissue formation were compared between the two algorithms and to clinically observed phenomena. Under loading conditions corresponding to a press-fit hip stem, the modified algorithm predicted bone ingrowth into approximately 25% of the pore space, which is similar to that reported in experimental studies, while the original algorithm was unstable. When micromotion at the bone-implant interface was simulated, 20 mum of transverse displacement resulted in soft tissue formation at the bone-implant interface and minimal bone ingrowth. In contrast, 10 and 5 mum of micromotion resulted in bone filling 40% of the pore space and a stable interface, again consistent with clinical and experimental observations.     

Influence of ingrowth regions on bone remodelling around a cementless hip resurfacing femoral implant

Hip resurfacing arthroplasty is an alternative to traditional hip replacement that can conserve proximal bone stock and has gained popularity but bone resorption may limit implant survival and remains a clinical concern. The goal of this study was to analyze bone remodelling patterns around an uncemented resurfacing implant and the influence of ingrowth regions on resorption. A computed tomography-derived finite element model of a proximal femur with a virtually implanted resurfacing component was simulated under peak walking loads. Bone ingrowth was simulated by six interface conditions: fully bonded; fully friction; bonded cap with friction stem; a small bonded region at the stem-cup intersection with the remaining surface friction; fully frictional, except for a bonded band along the distal end of the cap and superior half of the cap bonded with the rest frictional. Interface condition had a large influence on remodelling patterns. Bone resorption was minimized when no ingrowth occurred at the bone-implant interface. Bonding only the superior half of the cap increased bone resorption slightly but allowed for a large ingrowth region to improve secondary stability.     

Stiffness gradients in vascular bundles of the palm Washingtonia robusta

Palms can grow at sites exposed to high winds experiencing large dynamic wind and gust loads. Their stems represent a system of stiff fibrous elements embedded in the soft parenchymatous tissue. The proper design of the interface of the stiffening elements and the parenchyma is crucial for the functioning of the stem. The strategy of the palm to compromise between stiff fibre caps and the soft parenchymatous tissue may serve as a model system for avoiding stress discontinuities in inhomogeneous and anisotropic fibre-reinforced composite materials. We investigated the mechanical, structural and biochemical properties of the fibre caps of the palm Washingtonia robusta at different levels of hierarchy with high spatial resolution. A gradual decrease in stiffness across the fibre cap towards the surrounding parenchymatous tissue was observed. Structural adaptations at the tissue level were found in terms of changes in cell cross sections and cell wall thickness. At the cell wall level, gradients across the fibre cap were found in the degree of orientation of the microfibrils and in the lignin level and composition. The impact of these structural variations in the local material stiffness distribution is discussed.     

Numerical simulation of tissue differentiation around loaded titanium implants in a bone chamber

The application of a bone chamber provides a controlled environment for the study of tissue differentiation and bone adaptation. The influence of different mechanical and biological factors on the processes can be measured experimentally. The goal of the present work is to numerically model the process of peri-implant tissue differentiation inside a bone chamber, placed in a rabbit tibia. 2D and 3D models were created of the tissue inside the chamber. A number of loading conditions, corresponding to those applied in the rabbit experiments, were simulated. Fluid velocity and maximal distortional strain were considered as the stimuli that guide the differentiation process of mesenchymal cells into fibroblasts, chondrocytes and osteoblasts. Mesenchymal cells migrate through the chamber from the perforations in the chamber wall. This process is modelled by the diffusion equation. The predicted tissue phenotypes as well as the process of tissue ingrowth into the chamber show a qualitative agreement with the results of the rabbit experiments. Due to the limited number of animal experiments (four) and the observed inter-animal differences, no quantitative comparison could be made. These results however are a strong indication of the feasibility of the implemented theory to predict the mechano-regulation of the differentiation process inside the bone chamber.     

The early revascularization of membranous bone

The experimental finding that membranous onlay bone grafts maintain volume and viability to a greater extent than do endochondral grafts may be related to the more rapid vascularization of membranous bone. Microangiographic techniques were used to study the rates of vascularization of membranous and endochondral bone grafts in adult white New Zealand rabbits at 1, 3, 7, 14, and 21 days after bone grafting. Vascularization patterns were quantified microscopically using a modified point-counting technique. At 3 days, membranous bone grafts demonstrated vessel ingrowth from both soft tissue and host bone. Little ingrowth was seen in endochondral grafts. By day 7, 2.5 vessels per square were identified entering membranous grafts, while an average of 0.6 vessels per square were counted for endochondral bone grafts. At day 14, there was an average of greater than 20 vessels per square for membranous grafts versus 1.8 for their endochondral counterparts. At 21 days, the endochondral grafts demonstrated persistent avascular central areas not seen in membranous grafts. Membranous onlay bone grafts in the rabbit are more rapidly vascularized than endochondral grafts. This factor may affect the greater volume maintenance seen in experimental membranous grafts.     

Bone ingrowth simulation for a concept glenoid component design

Glenoid component loosening is the major problem of total shoulder arthroplasty. It is possible that uncemented component may be able to achieve superior fixation relative to cemented component. One option for uncemented glenoid is to use porous tantalum backing. Bone ingrowth into the porous backing requires a degree of stability to be achieved directly post-operatively. This paper investigates the feasibility of bone ingrowth with respect to the influence of primary fixation, elastic properties of the backing and friction at the bone prosthesis interface. Finite element models of three glenoid components with different primary fixation configurations are created. Bone ingrowth into the porous backing is modelled based on the magnitude of the relative interface micromotions and mechanoregulation of the mesenchymal stem cells that migrated via the bonded part of the interface. Primary fixation had the most influence on bone ingrowth. The simulation showed that its major role was not to firmly interlock the prosthesis, but rather provide such a distribution of load, that would result in reduction of the peak interface micromotions. Should primary fixation be provided, friction has a secondary importance with respect to bone ingrowth while the influence of stiffness was counter intuitive: a less stiff backing material inhibits bone ingrowth by higher interface micromotions and stimulation of fibrous tissue formation within the backing.     

Interstitial bone stress distributions accompanying ingrowth of a screen-like prosthesis anchorage layer

Recent development of screen-like bonded weaves of titanium wire for orthopaedic implant anchorage affords a unique opportunity for analytic studies of porous ingrowth micromechanics. The regular geometry of individual wires and the periodicity of the mesh weave are exploited in a series of two-dimensional finite element models, mapping interstitial bone stress fields as a function of ingrowth depth and wire size, shape, and spacing.

When the depth of bone ingrowth was less than one wire diameter, peak bone stresses always occurred at the leading (i.e. deepest) edge of bone ingrowth, immediately adjacent to the wire. As ingrowth depth approached a full wire diameter, peak local bone stresses were 2–9 times the nominal applied host bone stress, with greater stresses occurring for lower screen weave densities. Within multiple screen layers, the top layer consistently experienced the peak stress and transmitted most of the applied load, regardless of the number of underlying screen layers surrounded by bone. Neither wire size variations nor partial wire flattening substantially affected general trends in stress predictions.     

The influence of tibial component fixation techniques on resorption of supporting bone stock after total knee replacement

Periprosthetic bone resorption after tibial prosthesis implantation remains a concern for long-term fixation performance. The fixation techniques may inherently aggravate the "stress-shielding" effect of the implant, leading to weakened bone foundation. In this study, two cemented tibial fixation cases (fully cemented and hybrid cementing with cement applied under the tibial tray leaving the stem uncemented) and three cementless cases relying on bony ingrowth (no, partial and fully ingrown) were modelled using the finite element method with a strain-adaptive remodelling theory incorporated to predict the change in the bone apparent density after prosthesis implantation. When the models were loaded with physiological knee joint loads, the predicted patterns of bone resorption correlated well with reported densitometry results. The modelling results showed that the firm anchorage fixation formed between the prosthesis and the bone for the fully cemented and fully ingrown cases greatly increased the amount of proximal bone resorption. Bone resorption in tibial fixations with a less secure anchorage (hybrid cementing, partial and no ingrowth) occurred at almost half the rate of the changes around the fixations with a firm anchorage. The results suggested that the hybrid cementing fixation or the cementless fixation with partial bony ingrowth (into the porous-coated prosthesis surface) is preferred for preserving proximal tibial bone stock, which should help to maintain post-operative fixation stability. Specifically, the hybrid cementing fixation induced the least amount of bone resorption.     

Effect of tissue properties,shape and orientation of microcalcifications on vulnerable cap stability using different hyperelastic constitutive models

Approximately half of all cardiovascular deaths associated with acute coronary syndrome occur when the thin fibrous cap tissue overlying the necrotic core in a coronary vessel is torn, ripped or fissured under the action of high blood pressure. From a biomechanics point of view, the rupture of an atheroma is due to increased mechanical stresses in the lesion, in which the ultimate stress (i.e. peak circumferential stress (PCS) at failure) of the tissue is exceeded. Several factors including the cap thickness, morphology, residual stresses and tissue composition of the atheroma have been shown to affect the PCS. Also important, we recently demonstrated that microcalcifications (μCalcs>5 µm are a common feature in human atheroma caps, which behave as local stress concentrators, increasing the local tissue stress by at least a factor of two surpassing the ultimate stress threshold for cap tissue rupture. In the present study, we used both idealized µCalcs with spherical shape and actual µCalcs from human coronary atherosclerotic caps, to determine their effect on increasing the circumferential stress in the fibroatheroma cap using different hyperelastic constitutive models. We have found that the stress concentration factor (SCF) produced by μCalcs in the fibroatheroma cap is affected by the material tissue properties, μCalcs spacing, aspect ratio and their alignment relative to the tensile axis of the cap.     

A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture

The role of microcalcifications (μCalcs) in the biomechanics of vulnerable plaque rupture is examined. Our laboratory previously proposed (Ref. 44), using a very limited tissue sample, that μCalcs embedded in the fibrous cap proper could significantly increase cap instability. This study has been greatly expanded. Ninety-two human coronary arteries containing 62 fibroatheroma were examined using high-resolution microcomputed tomography at 6.7-μm resolution and undecalcified histology with special emphasis on calcified particles <50 μm in diameter. Our results reveal the presence of thousands of μCalcs, the vast majority in lipid pools where they are not dangerous. However, 81 μCalcs were also observed in the fibrous caps of nine of the fibroatheroma. All 81 of these μCalcs were analyzed using three-dimensional finite-element analysis, and the results were used to develop important new clinical criteria for cap stability. These criteria include variation of the Young's modulus of the μCalc and surrounding tissue, μCalc size, and clustering. We found that local tissue stress could be increased fivefold when μCalcs were closely spaced, and the peak circumferential stress in the thinnest nonruptured cap (66 μm) if no μCalcs were present was only 107 kPa, far less than the proposed minimum rupture threshold of 300 kPa. These results and histology suggest that there are numerous μCalcs < 15 μm in the caps, not visible at 6.7-μm resolution, and that our failure to find any nonruptured caps between 30 and 66 μm is a strong indication that many of these caps contained μCalcs.     

Experimental evaluation of ceramic calcium phosphate as a substitute for bone grafts.

Tricalcium phosphate (Synthos) is a bioceramic material which can be carved with a scalpel and wired into place as a bone graft would be. The process of bone replacement of the prosthesis begins with an ingrowth of cellular loose connective tissue, which is replaced later by dense connective tissue. Around the periphery of this dense fibrous connective tissue, osteoid tissue becomes evident and on later specimens this mixture seems to be converted to bone--which at first is in the form of spicules but later takes on the characteristics of lamellar bone (with tricalcium phosphate particles seen within its lacunae). The progressive replacement occurs in a circumferential pattern, but most heavily at the bone-prosthesis interface. Although the periosteum is beneficial, we do not feel that the major source of bone formation is as the soft tissue or subperiosteal area. The replacement of the tricalcium phosphate prosthesis is slower than we originally thought, or than reported by others. We have noted pockets of tricalcium phosphate, incompletely replaced, in dogs up to 18 months after implantation. We believe this may be related to the larger sized prostheses we used (2 x 2 cm blocks) with, therefore, longer distances that the ingrowth and calcification had to traverse.     

Polarized microtubule deposition coincides with wall ingrowth formation in transfer cells ofVicia faba L. cotyledons

Summary The epidermal transfer cells in developingVicia faba L. cotyledons are highly polarized. Extensive wall ingrowths occur on their outer periclinal walls and extend part way down both anticlinal walls. This ingrowth development serves to increase the surface area of the plasma membrane and thus maximize porter-dependent uptake of sugars from the seed apoplasm. In contrast, the inner periclinal walls of these transfer cells do not form wall ingrowths. We have commenced a study of the mechanisms responsible for establishing this polarity by first analysing the microtubule (MT) cytoskeleton in developing transfer cells. Thin sections of fixed cotyledons embedded in methacrylate resin were processed for immunofluorescence microscopy using monoclonal anti--tubulin and counterstained with Calcofluor White to visualize wall ingrowths. In epidermal cells of young cotyledons where wall ingrowths were yet to develop, MT labelling was detected around all cortical regions of the cell. However, in cells where wall ingrowths were clearly established, MT labelling was detected almost exclusively in cortical regions adjacent to the wall ingrowths. Little, if any, MT labelling was detected on the anticlinal or inner periclinal walls of these cells. This distribution of MTs was most prominent in cells with well developed wall ingrowths. In these cells, a subpopulation of MTs were also detected emanating from the subcortex and extending towards the wall ingrowth region. The possible role of MT distribution in establishing transfer cell polarity and wall ingrowth formation is discussed.Abbreviations MT microtubule     

Cortical bone viscoelasticity and fixation strength of press-fit femoral stems: finite element model

Many cementless implant designs rely upon a diaphyseal press-fit in conjunction with a porous coated implant surface to achieve primary or short term fixation, thereby constraining interface micromotion to such a level that bone ingrowth and consequent secondary or long-term fixation, i.e., osseointegration, can occur. Bone viscoelasticity, however, has been found to affect stem primary stability by reducing push-out load. In this investigation, an axisymmetric finite element model of a cylindrical stem and diaphyseal cortical bone section was created in order to parametrically evaluate the effect of bone viscoelasticity on stem push-out while controlling coefficient of friction (mu = 0.15, 0.40, and 1.00) and stem-bone diametral interference (delta = 0.01, 0.05, 0.10, and 0.50 mm). Based on results from a previous study, it was hypothesized that stem-bone interference (i.e., press-fit) would elicit a bone viscoelastic response which would reduce the initial fixation of the stem as measured by push-out load. Results indicate that for all examined combinations of mu and delta, bone viscoelastic behavior reduced the push-out load by a range of 2.6-82.6% due to stress relaxation of the bone. It was found that the push-out load increased with mu for each value of delta, but minimal increases in the push-out load (2.9-4.9%) were observed as delta was increased beyond 0.10 mm. Within the range of variables reported for this study, it was concluded that bone viscoelastic behavior, namely stress relaxation, has an asymptotic affect on stem contact pressure, which reduces stem push-out load. It was also found that higher levels of coefficient of friction are beneficial to primary fixation, and that an interference "threshold" exists beyond which no additional gains in push-out load are achieved.     

The Initiation, Development and Removal of Embryo Sac Wall Ingrowths in the Developing Seeds of Solanum nigrum L. An Ultrastructural Study

In developing seeds of Solanum nigrum L., wall ingrowths developedat the extreme micropylar and chalazal ends of the embryo sac.In the micropylar region, the wall ingrowths were initiatedat the three-celled endosperm stage starting at the base ofthe zygote then progressing for a short distance chalazalwards.They developed quickly with the most elaborate around the baseof the suspensor. The chalazal wall ingrowths developed alongthe surfaces of the chalazal cup, the antipodal cup and thehypostase. Those along the hypostase were initiated at the four-celled,those in the chalazal and antipodal cups at the 20-celled endospermstages. The most elaborate developed along the base of the antipodalcup; the most simple were along the base of the chalazal cup.Small electron-lucent invaginations of the plasmalemma whichlater became filled with fibrillar material, were the earliestindication of wall ingrowth formation. Removal of the wall ingrowthscommenced at the mid-globular stage of embryo development andwas completed by the mid-heart-shaped stage. In the micropylarregion, wall ingrowth removal was rapid, starting with the lossof the fibrillar component followed by the thinning of the cellwall. However, along the hypostase and antipodal cup, a heterogeneouslayer of varying electron densities and a thinner, more electrondense layer was laid down over the ingrowths. This was followedby the removal of the fibrillar component. The initiation, removaland location of the embryo sac wall ingrowths is discussed inconnection with understanding the nutritional relationshipsbetween maternal tissue, endosperm and embryo.Copyright 1995,1999 Academic Press Wall ingrowths, Solanum nigrum, transfer cells, zone of separation and secretion, hypostase     

Nucellar projection transfer cells in the developing wheat grain

Summary Transfer cells in the nucellar projection of wheat grains at 25 ±3 days after anthesis have been examined using light and electron microscopy. Within the nucellar tissue, a sequential increase in non-polarized wall ingrowth differentiation and cytoplasmic density was evident. Cells located near the pigment strand were the least differentiated. The degree of differentiation increased progressively in cells further removed from the pigment strand and the cells bordering the endosperm cavity had degenerated. Four stages of transfer cell development were identified at the light microscope level. Wall ingrowth differentiation followed a sequence from a papillate form through increased branching (antler-shaped ingrowths) which ultimately anastomosed to form a complex labyrinth. The final stage of wall ingrowth differentiation was compression which resulted in massive ingrowths. In parallel with wall ingrowth deposition cytoplasmic density increased. During wall deposition, paramural and multivesicular bodies were prominent and were in close association with the wall ingrowths. The degeneration phase involved infilling of cytoplasmic islets within the wall ingrowths. This was accompanied by complete loss of the protoplast. The significance of this transfer cell development for sucrose efflux to the endosperm cavity was assessed by computing potential sucrose fluxes across the plasma membrane surface areas of the nucellar projection cells. Transfer cell development amplified the total plasma membrane surface area by 22 fold. The potential sucrose flux, when compared with maximal rates of facilitated membrane transport of sugars, indicated spare capacity for sucrose efflux to the endosperm cavity. Indeed, when the total flux was partitioned between the nucellar projection cells at the three stages of transfer cell development, the fully differentiated stage III cells located proximally to the endosperm cavity alone exhibited spare transport capacity. Stage II cells could accommodate the total rate of sucrose transfer, but stage I cells could not. It is concluded that the nucellar projection tissue of wheat provides a unique opportunity to study transfer cell development and the functional role of these cells in supporting sucrose transport.Abbreviations CSPMSA cross sectional plasma membrane surface area - LPMSA longitudinal plasma membrane surface area - PTS tri-sodium 3-hydroxy-5,8,10-pyrenetrisulfonate