The mechanobiological effects of periosteal surface loads

We have developed an improved mechanobiological model of bone morphogenesis and functional adaptation that includes the influences of periosteum tension and pressure on bone formation and resorption. Previous models assumed that periosteal and endosteal bone deposition and resorption rates are governed only by the local intracortical daily stress or strain stimulus caused by cyclic loading. The new model incorporates experimental findings that pressures on periosteal surfaces can impede bone formation or induce bone resorption, whereas periosteal tensile strains perpendicular to bone surfaces can impede bone resorption or induce bone formation. We propose that these effects can produce flattened or concave bone surfaces in regions of periosteal pressure and bone ridges in regions of periosteal tension. The model was implemented with computer simulations to illustrate the role of adjacent muscles on the development of the triangular cross-sectional geometry of the rat tibia. The results suggest that intracortical stresses dictate bone size, whereas periosteal pressures may work in combination with intracortical stresses and other mechanobiological factors in the development of local bone cross-sectional shapes.     

Bone surface mapping method

Bone shape is an important factor to determine the bone's structural function. For the asymmetrically shaped and anisotropically distributed bone in vivo, a surface mapping method is proposed on the bases of its geometric transformation invariance and its uniqueness of the principal axes of inertia. Using spiral CT scanning, we can make precise measurements to bone in vivo. The coordinate transformations lead to the principal axes of inertia, with which the prime meridian and the contour can be set. Methods such as tomographic reconstruction and boundary development are employed so that the surface of bone in vivo can be mapped. Experimental results show that the surface mapping method can reflect the shape features and help study the surface changes of bone in vivo. This method can be applied to research into the surface characteristics and changes of organ, tissue or cell whenever its digitalized surface is obtained.     

Multiscale modeling of bone tissue with surface and permeability control

Natural biological materials usually present a hierarchical arrangement with various structural levels. The biomechanical behavior of the complex hierarchical structure of bone is investigated with models that address the various levels corresponding to different scales. Models that simulate the bone remodeling process concurrently at different scales are in development. We present a multiscale model for bone tissue adaptation that considers the two top levels, whole bone and trabecular architecture. The bone density distribution is calculated at the macroscale (whole bone) level, and the trabecular structure at the microscale level takes into account its mechanical properties as well as surface density and permeability. The bone remodeling process is thus formulated as a material distribution problem at both scales. At the local level, the biologically driven information of surface density and permeability characterizes the trabecular structure. The model is tested by a three-dimensional simulation of bone tissue adaptation for the human femur. The density distribution of the model shows good agreement with the actual bone density distribution. Permeability at the microstructural level assures interconnectivity of pores, which mimics the interconnectivity of trabecular bone essential for vascularization and transport of nutrients. The importance of this multiscale model relays on the flexibility to control the morphometric parameters that characterize the trabecular structure. Therefore, the presented model can be a valuable tool to define bone quality, to assist with diagnosis of osteoporosis, and to support the development of bone substitutes.     

Porous surface modified bioactive bone cement for enhanced bone bonding

Background

Polymethylmethacrylate bone cement cannot provide an adhesive chemical bonding to form a stable cement-bone interface. Bioactive bone cements show bone bonding ability, but their clinical application is limited because bone resorption is observed after implantation. Porous polymethylmethacrylate can be achieved with the addition of carboxymethylcellulose, alginate and gelatin microparticles to promote bone ingrowth, but the mechanical properties are too low to be used in orthopedic applications. Bone ingrowth into cement could decrease the possibility of bone resorption and promote the formation of a stable interface. However, scarce literature is reported on bioactive bone cements that allow bone ingrowth. In this paper, we reported a porous surface modified bioactive bone cement with desired mechanical properties, which could allow for bone ingrowth.

Materials and Methods

The porous surface modified bioactive bone cement was evaluated to determine its handling characteristics, mechanical properties and behavior in a simulated body fluid. The in vitro cellular responses of the samples were also investigated in terms of cell attachment, proliferation, and osteoblastic differentiation. Furthermore, bone ingrowth was examined in a rabbit femoral condyle defect model by using micro-CT imaging and histological analysis. The strength of the implant–bone interface was also investigated by push-out tests.

Results

The modified bone cement with a low content of bioactive fillers resulted in proper handling characteristics and adequate mechanical properties, but slightly affected its bioactivity. Moreover, the degree of attachment, proliferation and osteogenic differentiation of preosteoblast cells was also increased. The results of the push-out test revealed that higher interfacial bonding strength was achieved with the modified bone cement because of the formation of the apatite layer and the osseointegration after implantation in the bony defect.

Conclusions

Our findings suggested a new bioactive bone cement for prosthetic fixation in total joint replacement.     

Strain driven transport for bone modeling at the periosteal surface

Bone modeling and remodeling has been the subject of extensive experimental studies. There have been several mathematical models proposed to explain the observed behavior, as well. A different approach is taken here in which the bone is treated from a macroscopic view point. In this investigation, a one-dimensional analytical model is used to shed light on the factors which play the greatest role in modeling or growth of cortical bone at the periosteal surface. It is presumed that bone growth is promoted when increased amounts of bone nutrients, such as nitric oxide synthase (NOS) or messenger molecules, such as prostaglandin E₂ (PGE₂), seep out to the periosteal surface of cortical bone and are absorbed by osteoblasts. The transport of the bone nutrients is assumed to be a strain controlled process. Equations for the flux of these nutrients are written for a one-dimensional model of a long bone. The obtained partial differential equation is linearized and solved analytically. Based upon the seepage of nutrients out of the bone, the effect of loading frequency, number of cycles and strain level is examined for several experiments that were found in the literature. It is seen that bone nutrient seepage is greatest on the tensile side of the bone; this location coincides with the greatest amount of bone modeling.     

A method to estimate in vivo dynamic articular surface interaction

This paper describes a method to calculate and visualize the proximity of subchondral bone surfaces during dynamic movement. This method combines high-speed biplane radiographic image data and three-dimensional (3D) bone surface information derived from computed tomography to determine subchondral bone motion during dynamic activities. Knowledge of in vivo subchondral bone motion may be useful in the study of osteoarthritis, in biomechanical modeling, and in identifying normal and pathological joint mechanics. This method can be used to identify the regions of close contact during dynamic motion, to calculate the surface area of subchondral bone within close contact, and to determine the changing position of the close contact area during dynamic activities. None of this informations can be obtained using other currently available 3D motion analysis techniques. Example applications showing dynamic in vivo tibio-femoral bone surface motion during canine gait and human one-legged hopping are presented.     

Ligand-modified aminobisphosphonate for linking proteins to hydroxyapatite and bone surface

An increase in bone resorption is one of the main symptoms of osteoporosis, a disease that affects more and more individuals every day. Bisphosphonates are known to inhibit bone resorption and thus are being used as a treatment for osteoporosis. Aminobisphosphonates present a functionality that can be easily used for conjugation to other molecules, such as peptides, proteins, and ligands for protein recognition. In this study, an aminobisphosphonate conjugated with biotin was used as a model linker for protein attachment to bone. With this system, the interaction of biotinylated aminobisphosphonate with hydroxyapatite, a major mineral component of bone, was investigated. Quantification of the binding of aminobisphosphonate to hydroxyapatite was performed using a fluorescently labeled antibody for biotin. Additionally, the interaction of the biotinylated aminobisphosphonate with multiple treatments of cortical bone from the midshaft of a cow femur was studied. It was demonstrated that modified aminobisphosphonate reagents can bind hydroxyapatite and bone at high levels, while the biotin functionality is free to be recognized by the fluorescently labeled antibiotin antibody, suggesting that modified aminobisphosphonates could be used to link other peptides or proteins to the bone surface.     

Rapid activation of the medullary bone osteoclast cell surface by parathyroid hormone

Quantitative transmission electron microscope methods were used to determine the response of functionally inactive avian medullary bone osteoclasts to parathyroid hormone (PTH). Egg-lying Japanese quail were used during a period of the egg cycle when medullary bone was not being resorbed for egg shell calcification and when medullary bone osteoclasts were functionally inactive. Ruffled borders adjacent to bone surfaces were rarely, if ever, found on these cells. 20 min after the administration of PTH, over 70% of the osteoclast profiles had ruffled borders adjacent to bone surfaces. These ruffled borders were bounded by filamentous-rich "clear zones" and resembled ruffled borders found on functionally active cells. There was also a marked increase in plasma calcium levels after PTH administration. This study demonstrates that PTH stimulates the de novo generation of ruffled borders on osteoclasts in vivo and suggests that osteoclasts may be involved in the acute regulation of calcium metabolism by exogenous PTH.     

Propagation of surface fatigue cracks in human cortical bone

An understanding of how fatigue cracks grow in bone is of importance as fatigue is thought to be the main cause of clinical stress fractures. This study presents new results on the fatigue-crack growth behavior of small surface cracks (approximately 75-1000 microm in size) in human cortical bone, and compares their growth rates with data from other published studies on the behavior of both surface cracks and many millimeter, through-thickness large cracks. Results are obtained with a cyclically loaded cantilever-beam geometry using optical microscopy to examine for crack growth after every 100-500 cycles. Based on the current and previous results, small fatigue cracks appear to become more resistant to fatigue-crack growth with crack extension, analogous to the way the fracture resistance of cortical bone increases with crack growth. Mechanistically, a theory attributing such behavior to the development of bridges in the wake of the crack with crack growth is presented. The existence of such bridges is directly confirmed using optical microscopy.     

Microdamage in bone: surface analysis and radiological detection

Microdamage accumulation leads to reduced bone strength and fracture. Intact, damaged and Rose Bengal stained cortical bone specimens were studied using SEM and EDXA imaging. SEM coupled with EDXA studies showed selective labelling of surface damage due to binding of dye at free lattice sites. A series of novel iodinated X-ray contrast agent were synthesised. These agents demonstrated excellent stability, water solubility and lack of atropisomerism. Preliminary imaging studies, using cone-beam mu-CT, demonstrated their ability to provide visible contrast in the solid state on bone surfaces.     

Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression

Osteopontin (OPN) was expressed in murine wild-type osteoclasts, localized to the basolateral, clear zone, and ruffled border membranes, and deposited in the resorption pits during bone resorption. The lack of OPN secretion into the resorption bay of avian osteoclasts may be a component of their functional resorption deficiency in vitro. Osteoclasts deficient in OPN were hypomotile and exhibited decreased capacity for bone resorption in vitro. OPN stimulated CD44 expression on the osteoclast surface, and CD44 was shown to be required for osteoclast motility and bone resorption. Exogenous addition of OPN to OPN-/- osteoclasts increased the surface expression of CD44, and it rescued osteoclast motility due to activation of the alpha(v)beta(3) integrin. Exogenous OPN only partially restored bone resorption because addition of OPN failed to produce OPN secretion into resorption bays as seen in wild-type osteoclasts. As expected with these in vitro findings of osteoclast dysfunction, a bone phenotype, heretofore unappreciated, was characterized in OPN-deficient mice. Delayed bone resorption in metaphyseal trabeculae and diminished eroded perimeters despite an increase in osteoclast number were observed in histomorphometric measurements of tibiae isolated from OPN-deficient mice. The histomorphometric findings correlated with an increase in bone rigidity and moment of inertia revealed by load-to-failure testing of femurs. These findings demonstrate the role of OPN in osteoclast function and the requirement for OPN as an osteoclast autocrine factor during bone remodeling.     

Cells isolated from the endosteal bone surface of adult rats express differentiated osteoblastic characteristics in vitro

Endosteal bone surface cells were previously shown to be involved in the regulation of bone formation in humans. In this study, we have characterized the cells isolated from the endosteal bone surface in adult rats. Fragments of periosteum-free tibia were obtained from 4-, 6- and 9-month-old rats by collagenase digestion, and the phenotypic characteristics of the osteoblastic cells migrating from the endosteal bone surface were evaluated in culture. Endosteal bone surface cells present a strong alkaline phophatase (ALP) activity as shown by cytochemistry and measured biochemically. The cells synthesize high levels of osteocalcin as measured by radioimmunoassay. Osteocalcin production was increased after stimulation with 10 nM 1,25 dihydroxyvitamin D (1,25(OH)₂ D) and the response to 1,25(OH)2 D was similar at all ages. Endosteal cells from young adult rats (4 months old) but not from older rats (6 and 9 months old) showed increased cAMP production in response to 10 nM parathyroid hormone (PTH), suggesting an agerelated decrease in the PTH-responsiveness of the bone surface cells. Immunocytochemistry using specific antibodies showed that preconfluent endosteal bone cells from adult rats expressed collagen and noncollagenous bone proteins in culture in the absence of inducers. The cells synthesized mostly type-I collagen which remained localized intracellularly. Type-III collagen was only expressed at low levels. The bone surface cells also expressed osteocalcin and bone sialoprotein, two markers of differentiated osteoblasts, as well as osteonectin. Endosteal cells plated at high density and cultured for 21 days with 50 μg/ml ascorbic acid and 10 mM β-glycerophosphate formed multiple calcified nodules, as evidenced by von Kossa staining. This study shows that cells isolated from the endosteal bone surface of adult rats express in vitro characteristics of differentiated osteoblasts. These cell cultures can be used to study the dysfunctions of endosteal bone cells in relation to disorders of bone formation in adult rats.     

Scanning electron microscopic surface analysis of cryoconserved skull bone after decompressive craniectomy

Bone flaps removed during decompressive craniectomy are commonly frozen at ?80 °C and stored until cranioplasty. Histological integrity and regenerative capacity have been shown for cryoconserved bone. The effects of cryoconservation on the surface structure are unknown, although these might cause mechanical instability or facilitate bacterial adhesion. This study evaluates the surface structure of cryoconserved bone by scanning electron microscopy. Five patients were identified who could not receive their autologous bone flaps after decompressive craniectomy. These redundant bone specimens were obtained after cryoconservation for 6–8 months and the outer surface was analyzed by scanning electron microscopy. We found varying surface structures which did not correlate with any variables, such as patient age, gender or duration of freezing, and probably reflect physiological interindividual variation. Pathological findings, such as microscopic crack formation, were not observed. Cryoconservation for up to 8 months does not appear to alter the surface structure of skull bone on scanning electronic microscopy.     

The influence of acetabular cup material on pelvis cortex surface strains, measured using digital image correlation

Acetabular cup loosening is a late failure mode of total hip replacements, and peri-prosthetic bone deterioration may promote earlier failure. Preservation of supporting bone quality is a goal for implant design and materials selection, to avoid stress shielding and bone resorption. Advanced polymer composite materials have closer stiffness to bone than metals, ceramics or polymers, and have been hypothesised to promote less adverse bone adaptation. Computer simulations have supported this hypothesis, and the present study aimed to verify this experimentally.A composite hemi-pelvis was implanted with Cobalt Chromium (CoCr), polyethylene (UHMWPE) and MOTIS^®carbon-fibre-reinforced polyether etherketone (CFR-PEEK) acetabular cups. In each case, load was applied to the implanted pelvis and Digital Image Correlation (DIC) was used for surface strain measurement. The test was repeated for an intact hemi-pelvis. Trends in implanted vs. intact bone principal strains were inspected to assess the average principal strain magnitude change, allowing comparison of the potential bone responses to implantation with the three cups.The CFR-PEEK cup was observed to produce the closest bone strain to the intact hip in the main load path, the superior peri-acetabular cortex (+12% on average, R²=0.84), in comparison to CoCr (+40%, R²=0.91) and UHWMPE cups (?26%, R²=0.94). Clinical observations have indicated that increased periacetabular cortex loading may result in reduced polar cancellous bone loading, leading to longer term losses in periprosthetic bone mineral density. This study provides experimental evidence to verify previous computational studies, indicating that cups produced using materials with stiffness closer to cortical bone recreate physiological cortical bone strains more closely and could, therefore, potentially promote less adverse bone adaptation than stiffer press-fitted implants in current use.     

The effect of surface roughness on the stress adaptation of trabecular architecture around a cylindrical implant

The effect of implant-bone bonding and the effect of implant surface roughness on bone remodeling near the bone-implant interface were studied by using a surface remodeling theory and the boundary element method. The study has shown that implant attachment plays an important role in bone remodeling near the implant. It has been observed in animal experiments and in clinical situations that the remodeled trabecular bone architecture around a cylindrical implant could vary, on one hand, from a hub surrounding the implant with a set of external spokes to, on the other hand, a hubless situation in which a set of spokes attach directly to the implant. It is shown here that the difference in these structures may be attributed to differences in implant attachment. The results show that the bone with perfect bonding or roller boundary condition without a gap remodeled to a hubless spoke trabecular bone architecture. On the other hand, the roller boundary condition with a specified gap yielded a spoke trabecular architecture with a hub or ring surrounding the implant. These quantitative results mirror the experimental and clinical observations. It is concluded that the hub is a consequence of the gap and not a consequence of the lack of friction between the implant and the bone.     

Stress changes in the femoral head due to porous ingrowth surface replacement arthroplasty

Finite element stress analyses were conducted of the canine femoral head before and after implantation of various surface replacement-type components. The femoral head was replaced by four implant geometries; (a) shell, (b) shell with peg, (c) shell with rod, and (d) a new epiphyseal replacement design. All implants were modelled to simulate bony ingrowth along the underside of the shell and along the surfaces of the peg and rod. The results indicated that in the normal femur the forces are transferred from the articular surface through the femoral head cancellous bone to the inferior cortical shell of the femoral neck. After shell-type surface replacement, forces were transferred more distally at the rim of the shell and at the end of the peg or rod, thereby reducing the stresses in the proximal head cancellous bone. Computer simulation of bone remodelling due to proximal bone stress reduction was shown to accentuate the abnormality of the stress fields. Surface replacement with a lower modulus material created a less abnormal redistribution of bone stresses. The new epiphyseal replacement design resulted in stress distributions similar to those in the normal femoral head and minimal shear stresses at the implant/bone interface. These findings suggest that the epiphyseal replacement concept may provide better initial mechanical integrity and create a more benign milieu for adaptive bone remodelling than conventional, shell-type surface replacement components.     

Influence of RGD-containing oligopeptide-coated surface on bone formation in vitro and in vivo

New bone formation on an RGD-containing oligopeptide-coated surface in vitro and in vivo was investigated. The surface showed two-fold higher osteoblastic cell adhesion and differentiation in vitro, and revealed statistically significant in vivo bone formation compared with the control (P < 0.05).     

A generic 3-dimensional system to mimic trabecular bone surface adaptation

The paper presents the structure optimizing system based on surface remodelling. The grounds for algorithm formulation are given by the bone remodelling phenomenon leading to optimization of trabecular network in the bone. The assumptions, algorithms and limitations of the own mesh generator Cosmoprojector are described. Unlike other approaches, the system is able to mimic real bone evolution including tissue consolidation and separation. The article presents a closed system consisting of finite element mesh generation, decision criteria for structure adaptation and finite element analysis in parallel environment. It also provides some computation results obtained by using specially designed software.     

A generic 3-dimensional system to mimic trabecular bone surface adaptation

The paper presents the structure optimizing system based on surface remodelling. The grounds for algorithm formulation are given by the bone remodelling phenomenon leading to optimization of trabecular network in the bone. The assumptions, algorithms and limitations of the own mesh generator Cosmoprojector are described. Unlike other approaches, the system is able to mimic real bone evolution including tissue consolidation and separation. The article presents a closed system consisting of finite element mesh generation, decision criteria for structure adaptation and finite element analysis in parallel environment. It also provides some computation results obtained by using specially designed software.