Quantification of Bone and Peri-Implant Bone Strains Using Micro-Finite Element Analysis (Bepaling van de rekken in bot en rond botimplantaten door middel van micro-eindige elementen analyse)

Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;}Bone is a mechanosensitive tissue as it adapts itsmass, architecture and mechanical properties in response to changes in itsmechanical environment. The local mechanical environment in peri-implant bonetissue is considered as perhaps the most important regulating factor of thehealing processes that follow the surgical insertion of an endosseous implanteventually leading to its direct biological fixation, a condition known asimplant osseointegration. Understanding the role that mechanical load plays inbone might aid in treating and preventing bone loss due to osteoporosis ormicrogravity conditions and in favoring implant osseointegration. The effect ofmechanical loading on bone adaptation and peri-implant bone healing is commonlyinvestigated in vivo by means ofsmall animal models, in which controlled mechanical forces are applied and thebone response at the site of interest is evaluated. Recently bone adaptation toloading has also been investigated in small trabecular bone samples ex vivo . Within this context, this thesis was aimed at (i) quantifying the relationship between external mechanicalloading and induced bone strain in native bone of small animals as well asafter implant placement; (ii) evaluating the effect of mechanical loading onstructural quality and mechanical competence of trabecular bone, and investigatinghow the local mechanical environment is linked to the biological adaptationprocesses both at normal and micro-gravity conditions; (iii) assessing the qualityof murine bones interms of their apparent mechanical properties as it maybe used to quantify bone response to specific environmental, nutritional, andgenetic factors. In order to address the firstobjective of this thesis, we created andanalyzed specimen-specificmicrostructural finite element (µFE) models of the rat tibia compression model.The models were validated by means of strain gauge measurements. We demonstratedthat strain gauge measurements are very sensitive to the exact strain gaugelocation onthe bone. In contrast, we showed that the µFE models do not sufferfrom some of the experimental limitations such as the limited availability ingood bony locations for strain gauge placement, nor in the limitations ofplacing the strain gauge at the correct position, nor in the assessment ofstrain in just one direction. To evaluate the presence of an implant, wedeveloped and validated specimen-specific µFE models of the rat tibiae afterimplant insertion. For each specimen,different models were created corresponding to different representations of thebone implant interface. We found that irrespective of the specific interfaceproperties that were assigned to the models,the computational strainscorrelated highly to the experimental strains. Moreover, we demonstrated that athin peri-implant bone region with reduced Young s modulus effectivelyrepresents fro m a mechanical point of view the behaviour of the bone-implant interface immediately after implantinsertion. In order to address the secondobjective of this thesis, we evaluated the effects of mechanical loading ontrabecular bone samples after being cultured at normal and micro-gravity, andbeing subjected to either a static or a dynamic load. Bone structure wasquantified using microcomputed tomography-basedmorphological parameters andmechanical competence was quantified using m FE analysis; bone remodelling was assessedwith bone turnover markers. Overall, our findings suggest that bone response tomechanical loading was regulated mainly by an increase of bone formation atnormal gravity and by a decrease in bone resorption at micro-gravity.Finally,we found bone adaptation to be driven by low-magnitude high-frequency strainsand this to be valid both at normal and micro-gravity. In order to address the thirdobjective of this thesis, we investigated the use of three-point bending as amethod for assessing the global and the local mechanical properties of murinebones.W eprovided a short overview of the technology and evaluated the effects of thedevice geometry on the obtained mechanical parameters . A customizedthree-point bending setup was designed; the compliance of the machine wasdetermined. Furthermore, a loading protocol for testing murine bones wasdefined based on a study where we quantified the effects of loading cycles andbone positioning on bone apparent stiffness . In conclusion, this work has led to fourmain outcomes . First, we demonstrated that µFE modelscan provide accurate estimates of tissue-level strains in rat tibia whenexposed to controlled mechanical loading. We also demonstrated that the dataobtained by strain gauge measurements are strongly affected by strain gaugeplacements. Combining experimental measurements with highly accuratespecimen-specific finite element analyses can provide quantitative and reliablestrain data. Second, we have demonstrated that highly detailed specimen-specific finiteelement analyses can also provide accurate estimates of tissue-level strains inthe rat tibia after implant insertion. In addition, we showed that theperi-implant bone characteristics strongly affect the mechanical strain levelsoccurring in bone. Further investigations on the bone-implant interface areneeded if one would want to quantify the process of implant osseointegration. Third, we provided more insight into the remodelling processeswhich occur in trabecular bone when subjected to dynamic low-amplitudehigh-frequency load at micro-gravity. However, additional studies with extendedexperimental time and increased sample numbers are necessary to prove theanabolic potential of dynamic loading onbone quality and mechanical competence.Further investigations are indispensable for better understanding the linkagebetween mechanical stimuli and bone tissue response at normal andmicro-gravity. Fourth, a mechanical test set-up and loading protocol were defined for quantifyingthe mechanical competence of murine bones. Taken together we believe that these outcomes could help in optimizing the in vivo loading protocols that wouldprevent and counteract bone loss due toosteoporosis or disuse conditions.Furthermore, they could help in defining loading protocols that couldaccelerate implant osseointegration.nrpages: 193status: publishe