A repeated sampling bone chamber methodology for the evaluation of tissue differentiation and bone adaptation around titanium implants under controlled mechanical conditions

A repeated sampling bone chamber methodology was developed for the study of the influence of the mechanical environment on skeletal tissue differentiation and bone adaptation around titanium implants. Via perforations, bone grows into the implanted outer bone chamber, containing an inner bone chamber with a central test implant. An actuator—easily mounted on the outer bone chamber—allows a controlled mechanical stimulation of the test implant. After each experiment, the inner bone chamber—with its content—can be harvested and analysed. A new inner bone chamber with a central implant can be inserted consecutively in the outer bone chamber and a new experiment can start. Pilot studies led to a reliable surgical protocol and showed the applicability of the methodology, offering the possibility to study skeletal tissue differentiation and adaptation around implants under well-controlled mechanical conditions, and this protected from external loading. Repeated sampling of the bone chamber allows conducting several experiments within the same animal at the same site, thereby excluding subject- and site-dependent variability and reducing the amount of experimental animals.     

Assessment of mechanobiological models for the numerical simulation of tissue differentiation around immediately loaded implants

Nowadays, there is a growing consensus on the impact of mechanical loading on bone biology. A bone chamber provides a mechanically isolated in vivo environment in which the influence of different parameters on the tissue response around loaded implants can be investigated. This also provides data to assess the feasibility of different mechanobiological models that mathematically describe the mechanoregulation of tissue differentiation. Before comparing numerical results to animal experimental results, it is necessary to investigate the influence of the different model parameters on the outcome of the simulations. A 2D finite element model of the tissue inside the bone chamber was created. The differentiation models developed by Prendergast, et al. ["Biophysical stimuli on cells during tissue differentiation at implant interfaces", Journal of Biomechanics, 30(6), (1997), 539-548], Huiskes et al. ["A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation", Journal of Material Science: Materials in Medicine, 8 (1997) 785-788] and by Claes and Heigele ["Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing", Journal of Biomechanics, 32(3), (1999) 255-266] were implemented and integrated in the finite element code. The fluid component in the first model has an important effect on the predicted differentiation patterns. It has a direct effect on the predicted degree of maturation of bone and a substantial indirect effect on the simulated deformations and hence the predicted phenotypes of the tissue in the chamber. Finally, the presence of fluid also causes time-dependent behavior. Both models lead to qualitative and quantitative differences in predicted differentiation patterns. Because of the different nature of the tissue phenotypes used to describe the differentiation processes, it is however hard to compare both models in terms of their validity.     

A histological and biomechanical study of bone stress and bone remodeling around immediately loaded implants

Immediate loading(IL)increases the risk of marginal bone loss.The present study investigated the biomechanical response of peri-implant bone in rabbits after IL,aiming at optimizing load management.Ninety-six implants were installed bilaterally into femurs of 48 rabbits.Test implants on the left side created the maximal initial stress of 6.9 and 13.4 MPa in peri-implant bone and unloaded implants on the contralateral side were controls.Bone morphology and bone-implant interface strength were measured with histological examination and push-out testing during a 12-week observation period.Additionally,the animal data were incorporated into finite element(FE)models to calculate the bone stress distribution at different levels of osseointegration.Results showed that the stress was concentrated in the bone margin and the bone stress gradually decreased as osseointegration proceeded.A stress of about 2.0 MPa in peri-implant bone had a positive effect on new bone formation,osseointegration and bone-implant interface strength.Bone loss was observed in some specimens with stress exceeding 4.0 MPa.Data indicate that IL significantly increases bone stress during the early postoperative period,but the load-bearing capacity of peri-implant bone increases rapidly with an increase of bone-implant contact.Favorable bone responses may be continually promoted when the stress in peri-implant bone is maintained at a definite level.Accordingly,the progressive loading mode is recommended for IL implants.     

Computational simulation of internal bone remodelling around dental implants: a sensitivity analysis

This study aimed to predict the distribution of bone trabeculae, as a density change per unit time, around a dental implant based on applying a selected mathematical remodelling model. The apparent bone density change as a function of the mechanical stimulus was the base of the applied remodelling model that describes disuse and overload bone resorption. The simulation was tested in a finite element model of a screw-shaped dental implant in an idealised bone segment. The sensitivity of the simulation to different mechanical parameters was investigated; these included element edge length, boundary conditions, as well as direction and magnitude of the implant loads. The alteration in the mechanical parameters had a significant influence on density distribution and model stability, in particular at the cortical bone region. The remodelling model could succeed to achieve trabeculae-like structure around osseointegrated dental implants. The validation of this model to a real clinical case is required.     

Computational simulation of internal bone remodelling around dental implants: a sensitivity analysis

This study aimed to predict the distribution of bone trabeculae, as a density change per unit time, around a dental implant based on applying a selected mathematical remodelling model. The apparent bone density change as a function of the mechanical stimulus was the base of the applied remodelling model that describes disuse and overload bone resorption. The simulation was tested in a finite element model of a screw-shaped dental implant in an idealised bone segment. The sensitivity of the simulation to different mechanical parameters was investigated; these included element edge length, boundary conditions, as well as direction and magnitude of the implant loads. The alteration in the mechanical parameters had a significant influence on density distribution and model stability, in particular at the cortical bone region. The remodelling model could succeed to achieve trabeculae-like structure around osseointegrated dental implants. The validation of this model to a real clinical case is required.     

Numerical simulation of the remodelling process of trabecular architecture around dental implants

Dental implants may alter the mechanical environment in the jawbone, thereby causing remodelling and adaptation of the surrounding trabecular bone tissues. To improve the efficacy of dental implant systems, it is necessary to consider the effect of bone remodelling on the performance of the prosthetic systems. In this study, finite element simulations were implemented to predict the evolution of microarchitecture around four implant systems using a previously developed model that combines both adaptive and microdamage-based mechano-sensory mechanisms in bone remodelling process. Changes in the trabecular architecture around dental implants were mainly focused. The simulation results indicate that the orientational and ladder-like architecture around the implants predicted herein is in good agreement with those observed in animal experiments and clinical observations. The proposed algorithms were shown to be effective in simulating the remodelling process of trabecular architecture around dental implant systems. In addition, the architectural features around four typical dental implant systems in alveolar bone were evaluated comparatively.     

Numerical investigation of bone remodelling around immediately loaded dental implants using sika deer (Cervus nippon) antlers as implant bed

This study combines finite element method and animal studies, aiming to investigate tissue remodelling processes around dental implants inserted into sika deer antler and to develop an alternative animal consuming model for studying bone remodelling around implants. Implants were inserted in the antlers and loaded immediately via a self-developed loading device. After 3, 4, 5 and 6 weeks, implants and surrounding tissue were taken out. Specimens were scanned by μCT scanner and finite element models were generated. Immediate loading and osseointegration conditions were simulated at the implant-tissue interface. A vertical force of 10 N was applied on the implant. During the healing time, density and Young’s modulus of antler tissue around the implant increased significantly. For each time point, the values of displacement, stresses and strains in the osseointegration model were lower than those of the immediate loading model. As the healing time increased, the displacement of implants was reduced. The 3-week immediate loading model (9878 ± 1965 μstrain) illustrated the highest strains in the antler tissue. Antler tissue showed similar biomechanical properties as human bone in investigating the bone remodelling around implants, therefore the use of sika deer antler model is a promising alternative in implant biomechanical studies.     

Functional behaviour of bone around dental implants

Achieving a long-term stable implant interface is a significant clinical issue when there is insufficient cortical bone stabilisation at implant placement. Clinical outcomes studies suggest that the higher risk implants are those placed in compromised cortical bone (thin, porous, etc.) in anatomical sites with minimal existing trabecular bone (characterised as type IV bone). In establishing and maintaining an implant interface in such an environment, one needs to consider the impact of masticatory forces, the response of bone to these forces and the impact of age on the adaptive capacity of bone. These forces, in turn, have the potential to create localised changes in interfacial stiffness through viscoelastic changes at the interface. Changes in bone as a function of age (e.g. localised hypermineralised osteopetrosis and localised areas of osteopenia) will alter the communication between osteocytes and osteoblasts creating the potential for differences in response of osteoblastic cells in the older population. A key to understanding the biomechanical and functional behaviour of implants in the older population is to control the anticipated modelling and remodelling behaviour through implant design that takes into account how tissues respond to the mechanically active environment.     

Prediction of bone density around orthopedic implants delivering bisphosphonate

The fixation of an orthopedic implant depends strongly upon its initial stability. Peri-implant bone may resorb shortly after the surgery. This resorption is directly followed by new bone formation and implants fixation strengthening, the so-called secondary fixation. If the initial stability is not reached, the resorption continues and the implant fixation weakens, which leads to implant loosening. Studies with rats and dogs have shown that a solution to prevent peri-implant resorption is to deliver bisphosphonate from the implant surface.The aims of the study were, first, to develop a model of bone remodeling around an implant delivering bisphosphonate, second, to predict the bisphosphonate dose that would induce the maximal peri-implant bone density, and third to verify in vivo that peri-implant bone density is maximal with the calculated dose.The model consists of a bone remodeling equation and a drug diffusion equation. The change in bone density is driven by a mechanical stimulus and a drug stimulus. The drug stimulus function and the other numerical parameters were identified from experimental data. The model predicted that a dose of 0.3 μg of zoledronate on the implant would induce a maximal bone density. Implants with 0.3 μg of zoledronate were then implanted in rat femurs for 3, 6 and 9 weeks. We measured that peri-implant bone density was 4% greater with the calculated dose compared to the dose empirically described as best.The approach presented in this paper could be used in the design and analysis processes of experiments in local delivery of drug such as bisphosphonate.     

Method for histological preparation of bone sections containing titanium implants

A thin sectioning technique involving hand grinding has been developed to produce 20-40-microns-thick sections of bone-titanium implant sites. Components include: 1) surface staining of sections prior to mounting on slides so bone labels (oxytetracycline-HCl and 2,4-bis(N,N-dicarbomethyl)aminomethylfluorescein (DCAF] can be seen in sections viewed with transmitted light, 2) a pneumatic sample press for bonding sections to slides with a thin, uniform glue line and without trapped air bubbles, and 3) bonding methyl methacrylate embedded sections to clear acrylic slides with methyl methacrylate monomer to provide enhanced bond strength and grinding properties compared to those obtainable with glass slides. Sample cracking and distortion is minimized and the tissue-implant interface can be kept intact. The expense of start-up equipment for this technique is minimal.     

Evaluation of bone remodeling around single dental implants of different lengths: a mechanobiological numerical simulation and validation using clinical data

Algorithmic models have been proposed to explain adaptive behavior of bone to loading; however, these models have not been applied to explain the biomechanics of short dental implants. Purpose of present study was to simulate bone remodeling around single implants of different lengths using mechanoregulatory tissue differentiation model derived from the Stanford theory, using finite elements analysis (FEA) and to validate the theoretical prediction with the clinical findings of crestal bone loss. Loading cycles were applied on 7-, 10-, or 13-mm-long dental implants to simulate daily mastication and bone remodeling was assessed by changes in the strain energy density of bone after a 3, 6, and 12 months of function. Moreover, clinical findings of marginal bone loss in 45 patients rehabilitated with same implant designs used in the simulation (n = 15) were computed to validate the theoretical results. FEA analysis showed that although the bone density values reduced over time in the cortical bone for all groups, bone remodeling was independent of implant length. Clinical data showed a similar pattern of bone resorption compared with the data generated from mathematical analyses, independent of implant length. The results of this study showed that the mechanoregulatory tissue model could be employed in monitoring the morphological changes in bone that is subjected to biomechanical loads. In addition, the implant length did not influence the bone remodeling around single dental implants during the first year of loading.     

Modeling capsule tissue growth around disk-shaped implants: a numerical and in vivo study

We propose a new mathematical model that describes the growth of fibrous tissue around rigid, disk-shaped implants. A solution methodology based on an efficient regularized iterative method is presented to calibrate the model from some measurements of the capsule tissue concentration. Numerical results obtained with synthetic data are presented to demonstrate the ability of the proposed solution methodology to determine the model parameters corresponding to a given implant. In addition, numerical results obtained with experimental data are presented to illustrate the validity of the proposed model.     

Simulated bone remodeling around tilted dental implants in the anterior maxilla

Dental implants have to be placed with the long axis in different angulations due to the change in bone morphology. The objective of this study was to investigate the different bone remodeling response induced by the tilted dental implants and to assess whether it could lead to bone loss and implant failure. In this study, bone remodeling due to palato-labially inclined dental implants placed in the anterior maxillary incisor region was simulated. CT-based finite element models of a maxillary bone with dental implants were created herein. Five dental implants were placed at \(+10^{\circ }\), \(+5^{\circ }\), \(0^{\circ }\), \(-5^{\circ }\) and \(-10^{\circ }\), respectively. The remodeling progression was recorded and compared. Model \(-10^{\circ }\) (palatal side) shows the highest bone density values, but the inclined implant at \(+10^{\circ }\) (labial side) leads to significant bone loss. From a biomechanical perspective, it is speculated that a palatally inclined implant is more likely to enhance the bone density in the maxillary anterior region, but labial inclination of implant could jeopardize its stability.     

Predicting bone remodeling around tissue- and bone-level dental implants used in reduced bone width

The objective of this study was to predict time-dependent bone remodeling around tissue- and bone-level dental implants used in patients with reduced bone width. The remodeling of bone around titanium tissue-level, and titanium and titanium–zirconium alloy bone-level implants was studied under 100 N oblique load for one month by implementing the Stanford theory into three-dimensional finite element models. Maximum principal stress, minimum principal stress, and strain energy density in peri-implant bone and displacement in x- and y- axes of the implant were evaluated. Maximum and minimum principal stresses around tissue-level implant were higher than bone-level implants and both bone-level implants experienced comparable stresses. Total strain energy density in bone around titanium implants slightly decreased during the first two weeks of loading followed by a recovery, and the titanium–zirconium implant showed minor changes in the axial plane. Total strain energy density changes in the loading and contralateral sides were higher in tissue-level implant than other implants in the cortical bone at the horizontal plane. The displacement values of the implants were almost constant over time. Tissue-level implants were associated with higher stresses than bone-level implants. The time-dependent biomechanical outcome of titanium–zirconium alloy bone-level implant was comparable to the titanium implant.     

Development and design of a novel loading device for the investigation of bone adaptation around immediately loaded dental implants using the reindeer antler as implant bed

The assessment of the behavior of immediately loaded dental implants using biomechanical methods is of particular importance. The primary goal of this investigation is to optimize the function of the implants to serve for immediate loading. Animal experiments on reindeer antlers as a novel animal model will serve for investigation of the bone remodeling processes in the implant bed. The main interest is directed towards the time and loading-dependant behavior of the antler tissue around the implants. The aim and scope of this work was to design an autonomous loading device that has the ability to load an inserted implant in the antler with predefined occlusal forces for predetermined time protocols. The mechanical part of the device can be attached to the antler and is capable of cyclically loading the implant with forces of up to 100 N. For the calibration and testing of the loading device a biomechanical measuring system has been used. The calibration curve shows a logarithmic relationship between force and motor current and is used to control the force on the implant. A first test on a cast reindeer antler was performed successfully.     

Ectopic bone formation in titanium mesh loaded with bone morphogenetic protein and coated with calcium phosphate

The osteoinductive properties of porous titanium fiber mesh, with or without a calcium phosphate coating and loaded with recombinant human bone morphogenic protein-2 (rhBMP-2) or rhBMP-2 and native bovine BMP (S-300) were investigated in a rat ectopic assay model. A total of 112 calcium phosphate-coated and 112 noncoated porous titanium implants, either loaded with rhBMP-2 and S-300 or loaded with rhBMP-2 alone, were subcutaneously placed in 56 Wistar-King rats. The rats were killed 5, 10, 20, and 40 days postoperatively, and the implants were retrieved.Histologic analysis demonstrated that all growth factor and carrier combinations induced ectopic cartilage and bone formation at 5 and 10 days, respectively. At 20 days, bone formation increased and was characterized by trabecular bone and bone marrow-like tissue. At 40 days, more lamellar bone and hemopoietic bone marrow-like tissue were present. At both times, more bone had been formed in calcium phosphate-coated implants than in noncoated samples. Further, in rhBMP-2 and S-300-loaded specimens, bone formation was higher than in rhBMP-2 only-loaded specimens. In rhBMP-2 only-loaded specimens, bone formation was mainly localized inside the mesh material, whereas in specimens loaded with both rhBMP-2 and S-300, the bone was localized inside and surrounding the titanium mesh. The histological findings were confirmed by calcium content and alkaline phosphatase activity measurements. In addition, all specimens showed osteocalcin expression as early as 5 days postoperatively.Our results show that the combination of titanium mesh with BMPs can induce ectopic bone formation and that this bone formation seems to be similar to "enchondral" ossification. In addition, a thin calcium phosphate coating can have a beneficial effect on the bone-inducing properties of a scaffold material. Finally, rhBMP-2 and native BMP act synergistically in ectopic bone induction.     

Impaired osteoclast differentiation in subcutaneous implants of bone particles in osteopetrotic mutants

Because of its synchrony and relative homogeneity, the subcutaneous model of the resorption of mineral-containing, devitalized bone particles (BPs) is useful to evaluate the recruitment, differentiation, and activity of bone-resorbing, osteoclastic cells. Bone particles were prepared from normal rats or mice and were implanted in normal and osteopetrotic rats (ia, tl, op strains) or mice (mi strain). In addition, particles of microcrystalline hydroxyapatite or polymethylmethacrylate were implanted into tl and op mutants and their unaffected littermates.Non-decalcified histomorphometry of elicited tissues after 12 days revealed significantly less resorption in in each mutant. Enzyme histochemical assays revealed that only normal animals showed tartrate-resistant acid phosphatase-positive cells around the BPs. In agreement with this, only normal animals showed ruffled borders against the BPs. op and tl strains were tested for generation of foreign body giant cells in response to particulate hydroxyapatite or polymethylmethacrylate and no differences were found between mutant and normal animals. These mutants appear to have intact fusion of mononuclear progenitors.These data show impaired recruitment of osteoclasts by BP implants in several rodent strains of osteopetrotic mutants.     

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.