DE102006014169A1 - Reindeer antler bone changes examining method, involves loading implants over defined time through variable forces, which are exerted by load exerting device, and removing antler area containing implant, where removed area is examined - Google Patents

Abstract

The method involves inserting an implant in an antler of an antler carrying animal e.g. reindeer. The implants are mechanically loaded over a defined time through defined variable forces, which are exerted by a load exerting device attached at the antler. The antler area, which contains the implant is removed. The removed antler area is examined. The exposure takes place axially and/or unaxially with a force upto five hundred Newton. Independent claims are also included for the following: (1) a load exerting device for loading implants (2) an animal model for examining implants (3) an utilization of animal models for examining bone changes in the surrounding of the implants.

Description

described becomes a novel animal model, with which all types of bone wound healing and rebuilding phenomena implants, bone substitute materials and other fillers clinical, biomechanical and histological views can, without having to sacrifice the animal. additionally can Metabolic processes and evaluated the influence of growth factors on bone healing become. The invention further relates to a method for examination of implants using this model, and a device for execution of the procedure.

background

The Antler is the "headdress" of males Animals that are counted among the cervids - only the reindeer (Rangifer tarandus), both sexes wear antlers. Not to be confused it is with the headdress of sheep-like animals like the ibex, the chamois or the goat. This is made of horn, grows Lifelong with and will not be dropped, but can sometimes break.

By Control over the hormone testosterone grow from the forehead of the animals from rose bushes (cone-shaped bone structures) Bones, which with the advancing age of the animals and depending on Type of animal forming branches (ends, sprouts) or shovels can. Antlers are made of bone (not horn) and during the Growth phase over a short-haired skin, the bast, supplied by blood vessels. After graduation of growth, the bast dries and is absorbed by the animal on bushes and trees stripped (swept). In the autumn until late autumn of the year forms between antler and Rosenstock a demarcation line (parting line), where the antlers break off.

The Antlers of the reindeer are partly irregular and asymmetrical and at not identical to two animals. They are rod-shaped and widely branched; just the deepest rung forms a small shovel at the end of a pole, which is also called a "snow shovel" Antlers of the male is with a length from 50 to 130 centimeters much larger than that of the female, which only 20 to 50 inches long. The antlers of the male is repelled in the fall - that of the females in the spring; If necessary, do not both sides at the same time, so that the reindeer temporarily only one antler half Has.

In Regarding the bone remodeling processes around implants in general and immediate loaded dental implants in particular, so far no clear link yet of mechanical sizes and biological reactions. The very dynamic temporal change The bone structure through healing and bone remodeling can neither with experimental still using the standard finite element methods be detected directly. She expresses herself often e.g. only in the form of a relaxation, which is reflected in one Reduction of forces or an enlargement of the Deflections.

It So far, in particular, there is a lack of a simple animal model in which the effect of loading implants on the surrounding bone can be specifically investigated. This problem should be solved by the present Invention solved become.

Summary the invention

The The present invention relates to a method for simulating the Loading of implants, in which on antlers, preferably in reindeer antlers, implants advertised and charged under controlled conditions. For this purpose, preference is given to the compact, integrated and computer-controlled Loading device according to the embodiment (2) used over programmed stress logs cyclic deflections on the Apply implants.

• (1) ein Verfahren zur Untersuchung von Knochenveränderungen in der Umgebung von Implantaten, welche in Knochen implantiert werden, umfassend die Schritte (a) Einsetzen eines Implantats in das Geweih eines geweihtragenden Tiers (Cervide), bevorzugt eines lebenden geweihtragenden Tieres; (b) mechanische Belastung des Implantats über einen definierten Zeitraum durch definierte veränderbare Kräfte, welche von einer am Geweih angebrachten Belastungsvorrichtung ausgeübt werden; (c) anschließende Entfernung des Geweihbereich, welche das Implantat enthält; und (d) Untersuchung des entfernten Geweihbereichs;
• (2) eine Belastungsvorrichtung
• (3) ein Tiermodell zur Untersuchung von Implantaten, welche in Knochen implantiert werden, umfassend (i) ein geweihtragendes Tier, bevorzugt ein lebendes geweihtragendes Tier, in dessen Geweih mindestens ein Implantat inseriert ist; und (ii) eine Vorrichtung, welche auf das inserierte Implantat eine mechanische Belastung ausübt, bevorzugt die Belastungsvorrichtung gemäß Ausführungsform (2); und
• (4) die Verwendung des Tiermodells gemäß Ausführungsform (3) zur Untersuchung der Knochenveränderung in der Umgebung von Implantaten, zur Entwicklung und vorklinischen Prüfung neuer Knochenersatzmaterialien zur Knchenregeneration, neuer Implantate, insbesondere neuer Dentalimplantate, und zur Prüfung neuartiger Konzepte zur Behandlung von Patienten mit Implantaten.

The subject of the present invention is thus

• (1) a method for examining bone changes in the vicinity of implants implanted in bone, comprising the steps of (a) inserting an implant into the antler of an antler animal (Cervide), preferably a live antler animal; (b) mechanical loading of the implant over a defined period of time by defined variable forces exerted by an antler mounted load device; (c) subsequently removing the antler area containing the implant; and (d) examining the removed antler area;
• (2) a loading device
• (3) an animal model for examining implants implanted in bone comprising (i) an antler animal, preferably a live antler animal in whose antler at least one implant is inserted; and (ii) a device which applies a mechanical load to the inserted implant, preferably the loading device according to embodiment (2); and
• (4) The use of the animal model according to embodiment (3) for examining bone change in the vicinity of implants, for the development and preclinical testing of new bone replacement materials for bone regeneration, new implants, in particular new dental implants, and for testing novel concepts for treating patients with implants ,

Summary the figures

1 : Timing of an example procedure for investigating implants in reindeer antler with histological, histomorphometric and immunohistochemical examinations

2 : A schematic structure of an embodiment of a loading device according to the invention

3 : A schematic diagram of a microprocessor-controlled loading device according to the invention for simulating implant loads

Detailed description the invention

It will be a new animal model for implant and bone research presented. This is for non-consumable Animal studies suitable. The animal model may be next to the examination Dental issues also in all medical examinations to bone remodeling processes and bone metabolism processes Find application. The knowledge gained will help that clinical reliability of implants and, if appropriate, by targeted Improve design optimizations of the implants as well as the existing concepts to reconsider.

When Bone model in the method according to embodiment (1) the antler of All types of antler-bearing animals, especially all cervids, used become. The growth of the antler is a typical endochondral bone development, similar to the of human tubular bone [Li et al., 2001; Baxster BJ et al., 1999]. The growth takes place at the distal end of the antler branches. This growth zone becomes four zones just like the long human bone classified from distal to proximal: proliferating zone of the pre-dardbone, Zone of hypertrophic chondroblasts, zone of chondral ossification and zone of the woven bone. The woven bone is surrounded by the periosteum and is replaced by lamellar bone over time. By appositional growth from the periosteum decreases the diameter of the Antlers to [Ronning 1990]. Thus, the antler is from histological An adequate view Model for the representation of bone growth in the animal model.

Out biomechanical view are the material parameters of bone Cortex and cancellous bone relevant. Investigations by Currey [1989], Li [2003] and by Vashishth et al. [1997, 2000, 2003] to reindeer antlers have shown that the elastic and the breaking behavior substantially is comparable to the behavior of human bone. It Therefore, it is also very suitable for the examination from a biomechanical point of view the bone load around implants.

The in the context of the present invention preferred use of reindeer antlers in the process (1) offers many advantages. Antlers are the most antithetic Species only in males available. Exceptions are only the water turning, which never an antler has, as well as the reindeer (Rangifer tarandus, alternative name Ren or Karibou), in which both sexes have an antler. Because in an enclosure only a male Animals can be kept so reindeer have the big advantage that with female and male antler beams a larger animal population available in a small space stands.

The Antlers are branched poles that are dropped every year and then regrow. Bone examinations on antlers allow histological examinations without causing any permanent damage to the animal would. It should be emphasized that the experimental animals in contrast to conventional Investigation Methods For the subsequent ones histological and biomechanical studies should not be sacrificed have to.

Of the The advantage of a reindeer antler is that at the same biological and mechanical behavior the reindeer does not have solid dropping and growing times for the Has antlers. This means that in a smaller herd always animals whose antlers are favorable for the animal study Growth phase is.

Consequently you are not tied to the growing season, as is the case with deer or other antler-bearing animals.

The Size of reindeer together with easy domestication allows treatment without General anesthetic. The size of the reindeer varies a lot with the circulation area. The body length is sufficient from 120 to 220 centimeters, the shoulder height from 90 to 140 centimeters, the weight of 60 to 300 kilograms. Manual fixing of the Head and a therapy with surface anesthesia are in reindeer possible. Deer, moose or other antlers can access these minimally invasive Type can not be treated.

investigations on antlers compared to intraoral examinations provide the decisive advantage that the load on implants in the antler bone with a freely defined force and direction very accurately and purposefully can be applied. The animals are neither at the food intake still disturbed during locomotion by the loading device. Because antlers during the active growth phase are protected by the sensitive bast, avoid the animals unnecessary and in this phase very painful territorial fighting or contact with the antlers on foreign surfaces (for example, branches, Trees, etc.) and thus ensure the whereabouts of technical devices such as the loading device according to the embodiment (2) on the antlers.

The inventive method (1) includes in vitro studies of bone metabolism processes and Bone tissue changes on samples taken from the antlers, or on parts of the antlers. In particular, the temporal behavior is of implants under different loads in the bony Stock tissues examined. Therefore become histological after expiration of predefined exposure times in antlers and performed biomechanical investigations.

in the Following is the implementation of the method (1) presented using reindeer. All However, representations also apply without restriction of generality for others antlering animals. Reindeer are particularly suitable for the investigations of the invention, there the reindeer antler in its bone structure the human bone very similar is. In addition, the antler growth in reindeer is not a fixed Seasonally bound, bringing virtually consistent animals with antlers in desired Growth phase and thus also preparations for the Examinations available stand.

In the antler of a reindeer implants are inserted. In the same Treatment appointment will be three of these implants, each with one Loading device, preferably a loading device such as in embodiment (2). The load devices are programmed so that for longer periods (max 6 weeks on a single charge) autarkic intraoral loads be simulated. The implants can be in any direction and with different powers be charged. Thus, in a preferred embodiment in the first implant purely axial loads of 100 N sought, the second implant becomes excessively axial and the third implant with axial and non-axial forces loaded. After expiration of a predetermined time are under local anesthesia with an osteotomy saw or a rotating instrument the antler areas that the implants contained, taken. These preparations are further processed [Li C, Suttie JM, 2003] and for immunohistological detection of load-dependent Signaling substances used. In the same surgery appointment as well as described above 4 new implants used to osseodynamic changes while a twelve-week healing period to investigate. From the second week, calcium-affine dyes will be used intravenous injected. The preparation takes place as described before, the preparations be for the Histology further processed.

One Part of the preparations is in a particularly preferred aspect of the method before the histological preparation still experimental-biomechanically examined, to determine load / displacement characteristics. In one Another preferred aspect is surveying with suitable computed tomography Methods carried out to enable the reconstruction of implant / specimen geometries. The geometries can subsequently be converted into numerical models.

in the inventive method (1) the bone remodeling processes after implantation are examined. For the quantitative determination of bone remodeling processes in the implant bearing tissue preferably a histomorphometric analysis is carried out (corresponding to ASBMR = Nomenclature of the American Society for Bone and Mineral Research). Immunohistochemical studies are preferably used to the cellular Investigate processes in the implant area.

The Material properties of the bone are based on the composition the extracellular Matrix in particular on their degree of mineralization. This dynamic Operation is in a further preferred embodiment by means of bone chensequenzanalyse certainly. The combination of different examination methods allows finally in a particularly preferred aspect of the embodiment (1), assessing the complexity of bone regeneration processes.

In a very particularly preferred embodiment of the method (1) serve biomechanical investigations on the animal model according to the invention, and the comparison of these results with appropriate histological Investigations to interpret the bone remodeling processes around immediately loaded dental implants.

For the simulation of the implant loads, further, with embodiment (2) of the present invention, a self-sufficient, programmable loading device is provided, which is attached to the antler can be attached. In similar animal experiments, for example on sheep tibia, the experimental animals were repeatedly anaesthetized and cyclic loads of about 100 N applied to the implants inserted into the tibia via pull wires or lever constructions. Apart from the high burden on the animals due to repeated anesthesia, this procedure in the reindeer model would be completely impractical. Therefore, an independently operating loading device has been constructed that can be attached to the antlers and controlled by a microcomputer to apply the cyclic loads to the implant according to a programmed loading protocol.

In 2 an embodiment of a loading device according to the invention is shown schematically. The loading device 2 has an annular housing 3 on, with the help of closures 11 around a bone substance 15 can be arranged. In the bone substance 15 is an implant 17 planted. With the help of a fastening device 5 becomes the case 3 and thus the loading device 2 on the bone substance 15 attached. For this purpose, the fastening device 5 several cortical screws 7 on, extending through the case 3 extend and on the bone substance 15 issue.

On the case 3 is a drive unit 1 arranged, via a power transmission device 13 a force on the implant 17 exercises. The drive unit 1 For example, it may be a linear motor in the form of a piezo actuator. The power transmission device 13 For example, it consists of a push rod with a pressure plate attached to the implant 17 is present (in 2 not shown).

Structure and principle of operation of the loading device according to the invention are as follows: The annular housing 3 serves for the storage of a linear motor. The ser is equipped with a pressure plate, which is above the implant 17 is placed. This is the case 3 about surgical cortex screws 7 in the bone substance 15 anchored in an antler, for example. The force with which the linear motor on the implant 17 can be determined by the motor current. For this purpose, the power supply of the motor (for example, commercially available 9V battery) via a microprocessor (μP) with analog / digital converter (A / D) to control ( 3 ). By feedback, ie measurement of the motor current via the A / D converter and regulation of the same by the μP, defined load modes can be programmed and driven. With suitable linear motors forces up to 500 N can be realized. The external programming of the load protocols and the reading of the load history via a serial interface (RS232) by means of a computer unit, such as a portable computer. The power supply and μP are carried in a common housing the size of two matchboxes on a collar around the animal's neck. The autarkic load device can remain on the antler for up to 50 days without changing the power supply.

The animal model according to the invention according to embodiment (3) preferably comprises the loading device according to the embodiment (2).

The inventive method (1), the loading device according to the invention (2) and the animal model of the invention (3) are suitable for development and preclinical testing of new Bone replacement materials for bone regeneration, new implants and also novel treatment concepts.

The inventive method (1) can also be used to develop numerical models with which the tissue remodeling processes around the implants in antlers accordingly the situation in animal experiments can be simulated. By comparing the simulation results with the results of the experimental biomechanical study a validated theoretical model of bone remodeling processes Immediately loaded implants provided with which the Simulation of clinical stress situations and the prediction of possible Risk situations for immediately loaded implants is possible.

One preferred field of application of the method (1) is the clinical, biomechanical and histological assessment of the behavior of immediately loaded dental implants, to their function as anchoring of single tooth replacement mainly in the To optimize posterior region and the risk of implant loss to minimize.

Out the animal model (3) can be on antler basis new bone replacement materials to develop bone regeneration and implants.

The Invention is illustrated by the following examples, which but not limiting for the Subject of the invention should be.

Examples

Example 1: Loading device

A short-building piezotranslator (model P-830.20 from the company Physik Instrumente) serves as a loading device. With a maximum deflection of approx. 50 μm and a maximum load of 1000 N, this is an ideal device for carrying out con trolled cyclic loads, since the deflection can be controlled and regulated by the voltage. Also, the rise time of the deflection is extremely short, which allows the realization of very dynamic loads. Stepper motors, DC motors or linear adjusters are here much slower and must be provided with a considerable effort with, gears and other mechanics. In contrast, the piezo actuator can be used as a linear direct drive. For the control of the piezoelectric device is a single-board computer Fa. Phytec (Phytec nanoModul-164, with integrated analog / digital converter). The module is about the size of a check card and, with the integrated A / D converter, is ideally suited for the given task as controller of a compact, integrated device. Via a program that is loaded into the microcontroller, the A / D converter controls a power transistor (type SIPMOS from Siemens), which in turn regulates the voltage supply of the piezo actuator. Thus, the loading device completely self-sufficient cyclic loads over a defined period of time and with recorded load frequencies on the implants apply. Power is supplied by battery or battery packs.

Example 2: Experiments to reindeer antlers

Each time the antlers of a reindeer according to the in 1 provided implant plan with implants. The first preparations were taken after 14 days, the other preparations in dropping the antlers. In each case 4 screw implants were inserted into the ossified areas of the antler branches. At the same treatment appointment, three of these implants were each provided with a loading device. For the first implant, purely axial loads of a maximum of 100 N were aimed for. The second implant was loaded excessively axially (up to 500 N) and the third implant with axial and non-axial forces. After 14 days, the antlers containing the implants were removed with an osteotomy saw. In a further step, these preparations were dissected to form 1 mm thick bone discs containing bone cones in direct contact with the implant thread. These preparations were embedded in paraffin and used for immunohistological detection of stress-dependent signaling substances. As described above, 4 new implants were used at the same surgery appointment to study osteodynamic changes during a 12-week healing period. From the second week calcium-affine dyes were injected intravenously. The dyes were administered three times a week in a period of 2 weeks with the following sequence: tetracyclines 30 mg / kg, xylenol orange 90 mg / kg, DCAF 20 mg / kg body weight. A break of one week between two calcium-affine dyes was observed. When the antlers were dropped they were immediately collected and processed for further histological examination.

One Part of the preparations was still in the head CT before histological preparation or else in a μCT scanner measured. Also, these preparations were in the biomechanical Measurement setups were examined and the CT scans were used for the reconstruction of the preparations geometry for the FE analyzes.

Example 3: histochemistry

(A) Preparation of the tissues for the histology

To Removal of the samples was followed by immediate fixation in 4% buffered Paraformaldehyde at 4 ° C for at least 1 day and then the decalcification in 4% EDTA solution for 4 weeks. After that the preparations became embedded in paraffin-oriented. From the specimens were sagittal serial sections with a thickness of 5 microns made and selected Sections with overview dyeings (e.g., H.E.) stained. Thus, the assessment of bone remodeling is within the selected range vestibularly possible from the implant.

(B) Histochemical staining

to Identification of those involved in conversion operations Osteoclasts or Odontoklasten and their mononuclear precursors was on selected cuts a histochemical detection of tartrate-resistant acid phosphatase (TRAP), for the identification of osteoblasts or cementoblasts a detection of alkaline phosphatase (AP) performed.

(C) Immunohistochemical investigations

With Help of specific detection reactions were following immunohistochemical Investigations to prove the different markers of bone remodeling in a row performed by mechanical stress: cycloxygenase-2 (COX-2), endothelial nitric oxide synthase (eNOS), the growth hormone: insulin Like Growth Factor (IGF-1 and -2), Transforming Growth Factor-β (TGF-β) and Interleukin-6 (IL-6).

At chosen Sections were immunohistochemical evidence using commercially available pig-specific antibody after establishing appropriate protocols. Depending on antibody Evidence was provided by means of direct or indirect procedures and visualization using the ABC method.

(D) Morphometric evaluation

• – Anzahl der multinuklären Osteoklasten und ihre mononuklären Vorläufer,
• – Anzahl der Osteoblasten und
• – Fläche der Areale bzw. Anzahl der Zellen mit positiver Immunreaktion auf das Zytokin IL-6 und die Wachstumsfaktoren TGF-β, IGF-1 und -2, sowie die Enzyme eNOS und COX-2.

For the quantitative description of the recruited osteoclasts and osteoblasts morphometric analyzes were performed. The evaluations can be carried out computer-supported via an existing system. In each case, five sections with a spacing of 40 μm are evaluated for each preparation. The following parameters are determined in the selected bone region, which includes an area from the contact surface to the implant to the periosteum:

• - number of multinucleated osteoclasts and their mononuclear precursors,
• Number of osteoblasts and
• Area of the areas or number of cells with positive immune reaction to the cytokine IL-6 and the growth factors TGF-β, IGF-1 and -2, as well as the enzymes eNOS and COX-2.

Example 4: Fluorescence Studies

(A) Preparation of the tissues for the dynamic histomorphometry

The Four implants with the surrounding bone tissue were removed from the Sawed out antlers and fixed in 4% buffered paraformaldehyde at 4 ° C for 48 hours. Then took place a dehydration of the preparations in an ascending alcohol series (70-100%) and embedded in Methyl methacrylate. In the next Cuts are made along the longitudinal axis of the implant (Donath thin-section technique, 1988). The comparison of the osteodynamic findings around the implants is done by selecting three middle areas of the implant. These sections were at 10 μm ground thin.

(B) Dynamic histomorphometry

to quantitative description of osteodynamic bone remodeling processes morphometric evaluations performed. The following parameters are measured using a fluorescence microscope: percentage the bone apposition at the implant surface, percentage of bone attachment area, percentage double and triple labeled bone surface, mineral accumulation rate based on the cut surface and the percentage of bone resorption around the implant.

Example 5: Experimental and numerical studies of implant mobility

(A) Measurement of preparations

in the Framework of studies on the primary stability of dental implants was found that these are of the order of a few 100 microns can and composed of translations and rotations. With complete osseointegration is the distance between the oxide layer of titanium and the mineralized Bone tissue only a few nanometers. Depending on the local bone density and the number of threads in the implant becomes the order of magnitude the movements then only a few 10 microns. To the preparations with Measuring implants must therefore be able to measure set implants different resolutions and force areas are used. Such measuring systems are available in the form of MOMS and HEXMES available. They both allow the full three-dimensional Measurement of attacking force systems and the resulting deflections.

The functionality and the accuracy of the two measuring systems in terms of applications The biomechanical analysis of the implant behavior will be first Hand of different samples checked. When Samples can All types of bones are used which have a layer of cortical bone with underlying, sufficiently present cancellous bone. It can e.g. Pork jaw acquired in the slaughterhouse, processed and processed under standardized conditions become. Furthermore, segments of antlers with implants be provided and also be examined in the measurement setups. In these preparations are Implants are inserted and primary stability is measured. Only then will be analyzed the preparations obtained in the previous examples.

(B) reconstruction of Preparation geometry and sensitivity analysis

FE models of already measured preparations are generated. For this purpose, both the software described above CAGOG and a commercial program of the company Materialize, Leuven is used. Models based on histological sections (CAGOG) and head CT or μCT images (Materialize-MIMICS) are generated for calculation with the various existing FE packages. The geometry and density of the CT or μCT gives a very accurate FE model of the bone. For the geometry construction from the CTs the software MIMICS is needed. Furthermore, the mechanical tissue parameters can be calculated using Hounsfield units in the MIMICS program. The conversion of the density data of the CT into Young's modulus values can be based on the work of Rietbergen et al. respectively. The values can be automatically assigned to the corresponding element in MIMICS. The model developments are followed by investigations which estimate the sensitivity of the models against geometry changes, the influence of the number of elements and boundary conditions. This includes in particular the modeling of the boundary conditions in the area of the implant / bone interface.

Around It is necessary to obtain a convergence of results Variation of crosslink density, spongiosa and cortex to perform. The used material parameters on the basis of several preparations be verified. Furthermore, must the influence of Anisotropy of cancellous bone and cortical bone, inhomogeneities of Bone structures and possibly existing nonlinearities in the material behavior to be examined.

(C) validation of the numerical Results

Around compare the measured and calculated shifts they have to be able to from the same preparation come. At a match Theoretical and experimental shifts may be of this be assumed that under some fault tolerance the set up model is realistic, the material parameters used accurately reflect the behavior of all modeled structures, and that the calculated stress / strain patterns are actually occurring correspond. Thus, a comparison of the determined stress / distortion patterns done with clinical experience. Provide the clinical data Information about the chronological order of cultivated and degraded bones as well as its density and will allow a clearer statement To what extent the load distribution in the bone is involved in these processes. In addition, the comparison offers experimental and numerical results on pig segments and on antler segments an indication that to what extent the new animal model is considered mechanical and biomechanical may prove suitable.

Example 6: Development a bone remodeling theory to simulate implant healing

(A) Theoretical developments for the Description of bone remodeling around dental implants

amendments the bone structure allowed in the models to be developed - as well as in the biological System - only in the event of deviations from a state of equilibrium. This Equilibrium state is characterized by the fact that the Bone growth and dismantling process balance and no macroscopic changes mechanical properties or geometry may occur. By the introduction of the implant is the physiological burden of the implant Alveolar bone changed, because the periodontal ligament and the thus determined type of Load introduction omitted.

These Both points make a clear difference to the developed ones Models of orthodontic tooth movement: In these models was the main load and also the signal for bone remodeling in the periodontal ligament to see and the structure of tooth and periodontium was not changed. insofar can The developed routines are not transferred directly to the given task become. Furthermore, the orthodontic force application as a superposition of the normal strains of the stomatognathic system by chewing, swallowing etc. and thus calculated as an isolated problem. at The task to be considered here is the burden of alveolar bone but just from this normal, physiological Strains that result in a total strain of the bone over a add up a certain amount of time.

The occur cyclic deformations of the alveolar bone the preservation of the bone structure safely; So there is a balance between physiological stress and bone structure and shape. By introducing the implant this balance is disturbed, and Within the given distortion ranges, the equilibrium also changes between bone cultivation and degradation. This behavior is also to be expected in the animal model, by Inserting and loading the implant into the antler normal growth and the bone structure should be significantly influenced. By the controlled and logged load transfer via the The new devices described in example 1 also give the possibility accurately reproduce the load protocol in the numerical studies and to correlate the biological response with the mechanical stress levels.

As a result, is to develop a theory, first by the cyclic physiological loads can describe the maintenance of bone structure. The Developments are towards a distortion-controlled density change to operate the cancellous bone. This density change then manifests itself in a change the material parameters that in an iterative process to the changed mechanical To adapt to the situation. There are thresholds and limits within which the bone density exclusively decreases, remains constant or increases.

The work of this section deals with the development of mathematical and numerical relationships, the implementation in FORTRAN and the integration as adaptive finites Element or as an optimization loop in the FE system MARC.

(B) Model Generation and simulation calculations

The Working this section can essentially based on the results of the static FEM. The There generated FE model of the implant / bone composite can also have appropriate filters to that for be transferred to this work section used FE program. same for for the initial, ie at the start of a simulation calculation, to be used Material parameters of cancellous bone and cortical bone. Then it is the implant cyclically according to a physiological situation and at each load cycle the distortions are to be calculated and add up. The signal obtained in this way describes the order of magnitude of the local appeal for the bone remodeling, it is used to calculate the change in cancellous bone density evaluated. The resulting changed material parameters go in a new FE model of the implant / bone composite, which then back on the type already described is charged. This cycle will be like this long continued until the model is a new state of equilibrium has reached the density of cancellous bone and the associated material parameters So do not change anymore.

(C) validation of the statements of the model

• – Vergleich mit den initial berechneten Verzerrungsmustern und Belastungen aus der statischen FEM bei Einsatz verschiedener Implantate,
• – Vergleich der gemessenen und berechneten Beweglichkeiten eines Implantats im Tiermodell nach einer gewissen Standzeit desselben mit den Beweglichkeiten, die sich aus der Bone Remodeling Theorie nach der entsprechenden Zahl an Simulationszyklen ergibt,
• – Darstellung der Entwicklung der Dichteverteilung, die sich aus der Bone Remodeling-Theorie ergibt und Vergleich mit der Entwicklung der Dichteverteilung im Tiermodell und
• – Vergleich mit klinischen Beispielen (Implantatverlust, Implantatlockerung, abzuleiten aus Patientendokumentationen/Röntgenaufnahmen).

The informative value of the developed bone remodeling theory has to be assessed. Different results from the studies of this project as well as older results of other theoretical, experimental or clinical studies can be used. The following examinations are to be carried out:

• Comparison with the initially calculated distortion patterns and loads from the static FEM when using different implants,
• - Comparison of the measured and calculated mobility of an implant in the animal model after a certain lifetime thereof with the mobility resulting from the bone remodeling theory after the corresponding number of simulation cycles,
• - Presentation of the evolution of density distribution resulting from the bone remodeling theory and comparison with the development of density distribution in animal models and
• - Comparison with clinical examples (implant loss, implant loosening, to be deduced from patient documentation / X-rays).

For the works will be a very powerful Finite element program system requires that implementation the remodeling routines allowed. For this only the system MARC comes in question.

Example 6: Correlation of histology and biomechanics

In this final one Project section should be the biological findings with the biomechanical Results are correlated. First, as a standard procedure the topographic distribution of osteoclasts and osteoblasts determined histochemically. Then the distribution of the above Factors around the implants were examined immunohistochemically and statistically edited. These results are in the form of bar graphs shown, wherein the concentrations on the X-axis against the Height of Implants are applied. In further diagrams, the voltage and distortion distributions both in your components as well as averaged quantities ('von Mises tension', 'Total Strains') also as a plot against the height of the implant. These diagrams can each be about the Height of Implants in accordance to be brought.

By This type of representation is intended for each cell system studied and every marker as well Each tested load group (axially optimally loaded, unloaded, axially overloaded, axial and horizontally loaded) the correlation of biomechanical results be carried out with the cell biological reactions. This allows everyone anatomical region around the buccal bone the mechanical sizes and the concentrations of the markers or the number of cells with positive Assign reaction. This can be the direct link of calculated mechanical stimuli with in vivo observed biological Reactions can be achieved.

With the same procedure can the morphometric results of the osteodynamic bone remodeling processes the stress and distortion analysis are compared. The described Method allows for the first time an interpretation of the results of three aspects important in the bone remodeling around the dental implants, the so far only rudimentary examined as belonging together mechanisms have been. This can make a big contribution to it which mechanical quantity acts as a key stimulus, which cell regulatory activity is likely directly responds to this stimulus and which remodeling processes that Represent the end result of these biomechanical and biochemical parameters.

Example 7: Clinical Study about Immediately loaded implants in the posterior region

In the clinical study, occlusion concepts for immediately loaded implants in the posterior region will be developed. To the existing ones Checking and revising occlusion concepts for implants must also address the loading capacity of the implant abutment interface. It must be clarified whether the existing design principles can also be applied to the single tooth replacement in the posterior region and withstand the enormous mechanical stress in the chewing center. In particular, the load capacity of the connection system between implant and abutment plays a major role.

The prosthetic restoration of Ankylos implants is performed in the upper jaw and mandibular posterior region. At least one neighboring tooth and the antagonists have to to be kept in shape. The gap width is limited to 12 mm. Thus, a sufficient load capacity of the bone implant interfaces guaranteed is, should it allow the bone bearing, implants with a length of 11 mm and a diameter of at least 3.5 mm or at least 9.5 mm implants with a diameter of 4.5 mm or 8 mm implants with one Diameter of 5.5 mm to advertise. The bone quality should be Be D2-D3. D1 is also accepted. D4 only if a primary stability without further additive bone-condensing measures is achieved. For soft bones (D4) should be based on pre-cutting the thread in favor of a higher primary stability of the implant be waived. Very good primary stability is one of the most important Conditions for the success of immediate loading.

The Immediate loading of the implants takes place first by means of a temporary restoration. Here are only punctiform Contacts in MIK. The reduced occlusal surface design in oro-vestibular extension in combination with a flat camber incline prevents one laterotrusive power transmission the implant and thus reduces the applied torque when Mastication. The temporary will be for worn by the patient for about six weeks.

The definitive prosthetic restoration consists of Galvanokronen with Ceramic veneer, so that a passive fit of the denture guaranteed is. The occlusal surface design corresponds to the natural one Teeth with incorporated Zentrikkontakt and physiological Höckernigungen. The use of temporary Cement allows one conditionally removable superstructure. The X-ray checks with an individualized Right angle holder after insertion of the implant and three or nine months after the definitive prosthetic restoration gives one Information about the bone level. Continuous periotest measurements during the Inspection dates show any loosening of the implant on.

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Claims (25)

Method for examining bone changes around implants implanted in bone, comprising the steps (a) Inserting an implant in the Antler of an antler animal (Cervide; (b) mechanical Loading of the implant over a defined period of time by defined variable forces, which of an antler attached loading device are exercised; (c) subsequent removal the antler area containing the implant; and (d) investigation the distant antler area. Method according to claim 1, where the antler is a reindeer antler. Method according to claim 1 or 2, wherein the load is axial and / or non-axial, preferably with a force up to 500 N, more preferably with a force of 20 N to 150 N. Method according to one or more of claims 1 to 3, wherein in step (d) immunohistological examinations, in particular for proof of stress-independent Signaling substances, and / or biomechanical assays for determination of load and deflection characteristics. Method according to one or more of claims 1 to 4, in which at step (d) a repetition of the entire Method followed, and which is preferred for observation osseodynamischer changes while the healing phase is used. Method according to one or more of claims 1 to 5, wherein the implants are immediately loaded dental implants and which is used to assess the behavior of such implants under load. Loading device ( 2 ) for loading an implant ( 17 ) in a bone substance ( 15 ), - with a housing ( 3 ), - with one on the housing ( 3 ) arranged fastening device ( 5 ) for attaching the loading device to the bone substance ( 15 ), - with a loading means for exerting a force on the implant ( 17 ), characterized in that the loading means comprises a drive unit ( 1 ), which has a defined, variable force for loading the implant ( 17 ) generated. Loading device according to claim 7, characterized in that the loading means comprise a power transmission device ( 13 ), which receives the power from the drive unit ( 1 ) on the implant ( 13 ) transmits. Loading device according to claim 7 or 8, characterized characterized in that the generated force is a compressive force. Loading device according to claim 9, characterized in that the power transmission device ( 13 ) comprises a pressure plate attached to the implant ( 17 ) is present. Loading device according to one of claims 7 to 10, characterized in that the drive unit ( 1 ) is an electric motor. Loading device according to claim 11, characterized in that the electric motor is a linear motor, preferably a piezo actuator is. Loading device according to one of claims 7 to 12, characterized in that the loading means on the housing ( 3 ) is arranged. Loading device according to one of claims 7 to 13, characterized in that a control unit, preferably a microprocessor that controls the drive unit. Loading device according to claim 14, characterized in that the control unit is an analogue / digital converter has, over the motor current is measurable and adjustable. Loading device according to claim 14 or 15, characterized in that the control unit has an interface for coupling a computer unit. Loading device according to one of claims 14 to 16, characterized in that the control unit, the drive unit ( 1 ) according to defined load programs. Loading device according to one of claims 7 to 17, characterized by a power supply for the drive device ( 1 ) and / or the control unit, preferably a battery or an accumulator. Loading device according to one of claims 14 to 18, characterized in that the power supply and / or the Control unit away from the loading means, preferably in an animal collar, is arranged. Loading device according to one of claims 7 to 19, characterized in that the fastening device ( 5 ) Cortex screws ( 7 ), via which the loading device on the bone substance ( 15 ) is attached. Loading device according to one of claims 7 to 20, characterized in that the loading means the implant ( 17 ) - purely axial, - non-axial or - axially and non-axially loaded. Loading device according to one of claims 7 to 21, characterized in that that of the drive unit ( 1 ) forces up to 500 N, preferably 20 to 150 N. Animal model for the study of implants, which to be implanted in bone, comprising (i) an antithetical Animal in whose antlers at least one implant is inserted; and (Ii) a device which on the inserted implant a mechanical Exercise exercise ( "Loading device"). Animal model according to claim 23, wherein the loading device is a loading device according to a or more of the claims 7 to 22 is. Use of the animal model according to claim 23 or 24 for studying the bone change in the vicinity of implants, for the development and preclinical testing of new bone substitute materials and faithful materials for bone regeneration, in particular such antler-based materials, new implants, esp new dental implants, especially new antler-based implants, and for testing novel concepts for the treatment of patients with implants.