Le secteur médical est un domaine dynamique en constante évolution, nécessitant des améliorations continues de ses processus métier et une assistance intelligente aux acteurs impliqués. Ce travail de thèse se focalise sur le processus de soins nécessitant l’implantation d’une prothèse. La particularité de ce processus est qu’il met en interaction deux cycles de vie appartenant respectivement au domaine médical et celui de l’ingénierie. Ceci implique plusieurs actions de collaboration entre des acteurs métier très variés. Cependant, des problèmes de communication et de partage de connaissances peuvent exister en raison de l’hétérogénéité de la sémantique utilisée et des pratiques métiers propres à chaque domaine.Dans ce contexte, ce travail de thèse s’intéresse aux apports des approches d’ingénierie des connaissances et de gestion du cycle de vie du produit pour répondre aux problématiques sous-jacentes au processus de soins médicaux nécessitant l’implantation d’une prothèse. Pour se faire, un cadre conceptuel est proposé pour analyser les connexions entre les cycles de vie de maladie (domaine Médical)et de la prothèse (domaine d’ingénierie). Sur la base de cette analyse, un modèle sémantique sous forme d’une ontologie pour le domaine médical est définit dans le cadre de la construction d’une approche PLM à base de connaissances. L’application de cette proposition est démontrée à travers l’implémentation de quelques fonctions utiles dans un outil PLM du marché nommé AUDROS. / Medical sector is a dynamic domain that requires continuous improvement of its business processes and assistance to the actors involved. This research focuses on the medical treatment process requiring prosthesis implantation. The specificity of such a process is that it makes in connection two lifecyclesbelonging to medical and engineering domains respectively. This implies several collaborative actions between stake holders from heterogeneous disciplines. However, several problems of communication and knowledge sharing may occur because of the variety of semantic used and the specific business practices in each domain. In this context, this PhD work is interested in the potential of knowledge engineering and product lifecycle management approaches to cope with the above problems. To do so, a conceptual framework is proposed for the analysis of links between the disease (medicaldomain) and the prosthesis (engineering domain) lifecycles. Based on this analysis, a semantic ontology model for medical domain is defined as part of a global knowledge-based PLM approach proposition. The application of the proposition is demonstrated through an implementation of useful function in the AUDROS PLM software.

Bakgrund: Ledrörelse- och belastningsrestriktioner är vanliga efter en total höftprotesoperation och syftar till att undvika att höftleden luxerar eller att suturerad muskulatur släpper under tiden som mjukdelarna läker, vanligen 6 – 8 veckor. Proteser och operationsteknikerna har förändrats med åren vilket lett till att antalet postoperativa luxationer minskat, och därav har vissa ortopedkliniker i Sverige börjat frångå postoperativa ledrörelse- och belastningsrestriktioner. Syfte: Att kartlägga vilka ledrörelse- och belastningsrestriktioner som rekommenderas efter en total höftprotesoperation på svenska ortopedkliniker samt om restriktionerna har förändrats under de senaste fem åren. Metod: Studien genomfördes som en kvantitativ tvärsnittsstudie med hjälp av en egenformulerad validerad webbenkät. Huvudresultat: Av de 16 svarande klinikerna uppgav 81 % att de hade någon form av restriktion (ledrörelse- eller belastningsrestriktion) för sina höftprotesopererade patienter. Vanligast var ledrörelserestriktioner där 62 % av respondenterna svarade ja på frågan ”rekommenderar din enhet/klinik patienter som opereras med höftprotesoperation några ledrörelserestriktioner”. Motsvarande siffra för belastningsrestriktioner var 50 %. En total avsaknad av restriktioner förekom hos 19 % av de svarande klinikerna. 63 % av klinikerna svarade att belastningsrestriktionerna hade förändrats för mer än 10 år sedan medan 50 % av klinikerna svarade att ledrörelserestriktionerna hade förändrats de senaste 5 åren. Resultatet i vår studie tydde på att användandet av postoperativa restriktioner har minskat. Den vanligaste förändringen var en minskning av användandet av postoperativa ledrörelserestriktioner, vilket hade skett hos 60 % av respondenterna. Konklusion: Vår studie visade att 4 av 5 svenska ortopedklinikerna som deltog i vår enkätstudie använde sig av ledrörelse- eller belastningsrestriktioner efter en höftprotesoperation och att 1 av 5 inte använde restriktioner. Hälften av klinikerna har förändrat ledrörelserestriktionerna de senaste fem åren, och färre än 40 % har förändrat belastningsrestriktionerna. / Background: Joint movement- and load precautions are common after a total hip arthroplasty and aims to prevent dislocation of the hip and to prevent the loss of sutured muscles while the soft tissue heal, usually 6-8 weeks. Prosthesis and surgical technics have changed over the years, which had led to a reduced number of postoperative hip dislocations and hence have some orthopedic clinics in Sweden begun abandon postoperative joint movementand load precautions. Aim: A mapping of the use of joint movement- and load precautions in Swedish orthopedic clinics and if there has been any changes in precautions during the last five years. Method: The study was conducted as a quantitative cross-sectional study with the help of a selfdeveloped validated online survey. Result: 81 % of the 16 respondent clinics stated they had some form of precautions (joint movement- or load precautions) for their hip replaced patients. The most common precaution was joint movement where 62% of respondents answered yes to the question "Does your unit/Clinic recommend patients undergoing surgery with total hip replacement any joint movement precautions". The corresponding figure for load precautions was 50%. A total absence of restrictions occurred in 19 % of the respondent clinics. 63 % responded that modifications of load precautions took place for more than 10 years ago while 50 % responded that the modifications of joint movement precaution took place over the past 5 years. The result in our study indicated that the use of precautions had decreased. The most common change was a decrease in jointmovementprecautions that occurred with 60 % of the respondents. Conclusion: In our study we found that 4 out of 5 Swedish orthopaedic clinics who participated in our survey recommended joint movement- or load precautions after a hip replacement and it also showed that 1 out of 5 didn´t recommend precautions. Half of the clinics had changed the movement precautions during the past five years, and less than 40 % had changed the load precautions.

Cette étude à pour but de développer un concept de stent atraumatique pour le remplacement percutanée de la valve aortique. Le stent est obtenu à partir de brins de Nitinol tressés, ce qui lui permet, de part sa géométrie et sa structure, d'être compressible, auto-expansible, et atraumatique. Le principe de fabrication des prototypes et les contraintes qui lui est associé sont présentées. Les performances de ces prototypes, en terme d'ancrage, de régurgitation statique et de régurgitation dynamique sont ensuite évaluées par des essais in vitro, pour lesquel le banc de test en flux pulsé a été optimisé afin de prendre en considération la compliance de la racine aortique. Les résultats obtenus permettent de mettre en évidence les différents paramètres de fabrication stent, tant au niveau dimensionnel (hauteur du cylindre, angle du cône...) qu'au niveau structurel (rigidité), qui ont une influence significative sur le comportement de l'endoprothèse. / The goal of this work is to develop an atraumatic stent concept for percutaneous aortic valve replacement. Shape setted braided nitinol wires, thanks to their specific geometry and elasticity, allows stent's compressibility, self deployment and aortic root preservation. Prototypes manufacturing technique and relatives constraints are presented. Performance of the obtained prototypes are evaluated in vitro, in terms of sealing, static and dynamic regurgitation. More specifically, the pulsatile bench testing has been optimized to take in account the compliant constraint of the aortic valve environment. The results bring to the fore which are the dimensions (head height, cone angle...) and the structures features that do influence the endoprosthesis behavior significantly.

Intuitive prosthetic control is limited by the inability to easily convey intention and perceive physical requirements of the task. Rather than providing haptic feedback and allowing users to consciously control every component of manipulation, relegating some aspects of control to the device may simplify operation. This study focuses on the development and testing of a control scheme able to identify object stiffness and regulate impedance. The system includes an algorithm to detect the apparent stiffness of an object, a proportional nonlinear EMG control algorithm for interpreting a user’s desired grasp aperture, and an antagonistically acting impedance controller. Performance of a testbed prosthetic simulation used to controllably extrude pastes of different properties from a compliant tube was compared to that of the non-dominant human hand. The paste volume extrusion error and response time to perform the task were recorded for comparison. Statistical analysis using (GEE) and (TOST) suggests the prosthetic controller and human hand performed similarly along these metrics. Performance differences in the trials were more strongly correlated to tube type and repetition block. The results suggest that the developed controller allows users to perform a controlled squeezing task at a level comparable to the human hand with minimal training. It also suggests that a priori stiffness estimation acquired through quick palpations may be sufficient for effective control during simple manipulation. The lack of a learning curve suggests that the development of systems that automatically control aspects of mechanical interaction may offer users more advanced control capabilities with low cognitive load.

It has been postulated that the control of thrombus formation on molecularly engineered surfaces is an important step in developing clinically durable small-diameter vascular prostheses. This has led to designing a membrane-mimetic assembly that contains physiological regulators of blood coagulation, thrombomodulin (TM) and heparin, to provide strategies for generating actively antithrombogenic surfaces. The membrane-mimetic construct contains polymeric phospholipid monolayer on an alkylated polyelectrolyte multilayer supported by planar substrate such as glass or silicone. When incorporated with TM, the model platform exhibited the biological function by catalyzing activation of protein C. Surface TM activity was extensively investigated at physiologic shear rates (50 sec-1 and 500 sec-1). Significantly, reaction rates become saturated at TM surface densities greater than or equal to ~ 800 fmole/cm2 due to due to a transport limitation. Based on the similar membrane-mimetic construct, a functional heparinized surface was designed as an alternative anticoagulant system. Immobilization of heparin onto membrane-mimetic surfaces was achieved through biotin-streptavidin binding specificity. Activity of surface heparin to facilitate thrombin inactivation was investigated at shear rates of 50 and 500 sec-1. Significantly, rate of thrombin decay becomes saturated when the surface coverage of heparin is higher than 4.4 pmole of heparin per cm2. We further investigated the effects of surface bound TM and heparin on tissue factor (TF) -induced thrombin generation in a flow model. Specifically, TF positioned over a 2 x 6 mm2 upstream region as a trigger for thrombin generation and TM and/or heparin positioned over the remaining downstream (34 x 6 mm2) portion of the test film. Compared to TF alone surface, thrombin generation was profoundly reduced in the presence of surface bound TM and/or heparin. Significantly, thrombin production was maximally inhibited more than 85% in the presence of TM and heparin, possibly due to anticoagulant synergism of both anticoagulants. We believe that current membrane-mimetic systems can potentially create actively antithrombogenic surfaces.

Bileaflet mechanical heart valves (BMHVs), though a life-saving tool in treating heart valve disease, are often associated with serious complications, including a high risk of hemolysis, platelet activation, and thromboembolism. One likely cause of this hyper-coagulative state is the nonphysiologic levels of stress experienced by the erythrocytes and platelets flowing through the BMHVs. Research has shown that the combination of shear stress magnitude and exposure time found in the highly transient leakage jet emanating from the b-datum gap during valve closure is sufficient to cause hemolysis and platelet activation. Regions of flow stasis in the valve vicinity may also allow activated platelets to aggregate and form thrombus. This thesis addresses the hypothesis that passive flow control may have the potential to reduce flow-induced thrombogenicity by altering the fluid mechanics of bileaflet mechanical heart valves. To test this hypothesis, a steady model of the regurgitant b-datum line jet was developed and studied. This model served as a test bed for various vortex generator array designs. The fluid mechanics of the b-datum line jet model was investigated with flow visualization and particle image velocimetry. In vitro tests with whole human blood were performed with and without the vortex generators in order to determine how the presence of the passive flow control affected the propensity of the blood to form thrombus. An effort was then made to correlate the fluid mechanics of the jet model with the procoagulant potential results from the blood experiments. The effect of the vortex generators on the fluid mechanics of the valve under physiologic pulsatile conditions was also investigated via flow visualization in the Georgia Tech Left Heart Simulator. By studying a steady model of the regurgitant b-datum line jet, it was found, using an in vitro system with whole human blood, that the presence of vortex generators significantly decreased the blood's propensity for thrombus formation. The potential of applying passive flow control to cardiovascular hardware in order to mitigate the injurious effects of shear-induced platelet activation is thus demonstrated. The investigation into the effect of vortex generators on the fluid mechanics of the b-datum line jet showed that the jet oscillated aperiodically and that the effect of the applied flow control was played out at both the scale of the chamber (large-scale) and on the scale of the vortex generator fins (small-scale). On the large scale, the presence of vortex generators appeared to decrease the magnitude or frequency of jet oscillation, thereby stabilizing the jet. After removing the effect of the large-scale oscillations via phase averaging, the effect of the vortex generators on the small scale was examined. On the small scale, the jet without flow control was found to have higher levels of velocity RMS, particularly on the jet periphery, and higher levels of Reynolds shear stress. It is proposed that the vortex generators effect this change by generating vorticity in the plane of the jet. This vorticity is theorized to stabilize the jet, delaying roll-up of the jet shear layer which occurs via the Kelvin-Helmholtz instability. The method by which the vortex generators acted on the fluid mechanics of the steady jet system to decrease the blood's procoagulant potential was investigated via flow visualization and DPIV. The results from these studies implicate two possible mechanisms by which the vortex generators may act. First, the peak turbulent shear stresses in the jet were reduced by 10-20% with the application of vortex generators. Even if only a few platelets were activated in each passage through the valve, the cumulative effect of this difference in peak stresses after many passes would be greatly magnified. Thus, this reduction in turbulent shear stresses may be sufficient to explain the change seen in the blood's procoagulant potential with the application of passive flow control. It is suspected, though, that the second mechanism is dominant. The flow fields revealed that the presence of the vortex generators delayed or prevented the roll-up of the Kelvin-Helmholtz instability in the b-datum jet's shear layers into discrete vortices. By doing so, it is thought that opportunities for the interaction of activated and unactivated platelets entrained in these vortices were prevented, thereby inhibiting further propagation of the coagulation cascade. Even if the rate at which platelets were activated was similar for cases with and without flow control, it seems that the flow fields experienced by the platelets subsequent to activation can determine the level of procoagulant potential. Under the steady conditions observed in this experiment, the jet influenced by vortex generators was thus shown to induce significantly lower levels of procoagulant potential.

Spinal cord injury results in complete failure of the central neurons to regenerate and is associated with cyst formation and enlargement of the trauma zone. In contrast to the spinal cord, axons in the injured peripheral nerve have the capacity to undergo some spontaneous regeneration. However, significant post-traumatic loss of nervous tissue causing long nerve gap is one of the main reasons for the poor restoration of function following microsurgical repair of injured nerves. The present thesis investigates the effects of biodegradable conduits prepared from fibrin glue and poly-beta-hydroxybutyrate (PHB) in combination with cultured Schwann cells, mesenchymal stem cells and extracellular matrix molecules on regeneration after spinal cord and peripheral nerve injury in adult rats. At 4-8 weeks after transplantation into the injured spinal cord, the PHB conduit was well integrated into the cavity but regenerating axons were found mainly outside the PHB. When suspension of BrdU-labeled Schwann cells was added to the PHB, regenerating axons filled the conduit and became associated with the implanted cells. Modification of the PHB surface with extracellular matrix molecules significantly increased Schwann cell attachment and proliferation but did not alter axonal regeneration. To improve the labeling technique of the transplanted cells, the efficacy of fluorescent cell tracers Fast Blue, PKH26, Vibrant DiO and Cell Tracker™ Green CMFDA was evaluated. All tested dyes produced very efficient initial labeling of olfactory ensheathing glial cells in culture. The number of Fast Blue-labeled cells remained largely unchanged during the first 4 weeks whereas the number of cells labeled with other tracers was significantly reduced after 2 weeks. After transplantation into the spinal cord, Fast Blue-labeled glial cells survived for 8 weeks but demonstrated very limited migration from the injection sites. Additional immunostaining with glial and neuronal markers demonstrated transfer of the dye from the transplanted cells to the host tissue. In a sciatic nerve injury model, the extent of axonal regeneration through a 10mm gap bridged with tubular PHB conduit was compared with a fibrin glue conduit. At 2 weeks after injury, the fibrin conduit supported similar axonal regeneration and migration of the host Schwann cells compared with the PHB conduit augmented with a diluted fibrin matrix and GFP-labeled Schwann cells or mesenchymal stem cells. The long-term regenerative response was evaluated using retrograde neuronal labeling. The fibrin glue conduit promoted regeneration of 60% of sensory neurons and 52% of motoneurons when compared with the autologous nerve graft. The total number of myelinated axons in the distal nerve stump in the fibrin conduit group reached 86% of the nerve graft control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89%, respectively. When a fibrin conduit was used to bridge a 20mm sciatic nerve gap, the weight of gastrocnemius muscle reached only 43% of the nerve graft control. The morphology of the muscle showed more chaotic appearance and the mean area and diameter of fast type fibers were significantly worse than those of the corresponding 10mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. In summary, these results show that a PHB conduit promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal growth after transplantation into the injured spinal cord. The data suggest an advantage of the fibrin conduit for the important initial phase of peripheral nerve regeneration and demonstrate potential of the conduit to promote long-term neuronal regeneration and muscle recovery.

No description available.

The law of bone remodeling, commonly referred to as Wolff's Law, asserts that the internal trabecular bone adapts to external loadings, reorienting with the principal stress trajectories to maximize mechanical efficiency, thereby creating a naturally optimum structure. The primary objective of the research was to utilize an advanced structural optimization algorithm, called design space optimization (DSO), to create a numerical framework to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur and analyze the results to determine the validity of Wolff's hypothesis. DSO optimizes the layout of material by iteratively distributing it into the areas of highest loading, while simultaneously changing the design domain to increase computational efficiency. The result is a "fully stressed" structure with minimized compliance and increased stiffness. The large-scale computational simulation utilized a 175µm mesh resolution and the routine daily loading activities of walking and stair climbing. The resulting anisotropic human trabecular architecture was compared to both Wolff's trajectory hypothesis and natural femur data from the literature using a variety of visualization techniques, including radiography and computed tomography (CT). The remodeling predictions qualitatively revealed several anisotropic trabecular regions comparable to the natural human femurs. Quantitatively, the various regional bone volume fractions from the computational results were consistent with CT analyses. The strain energy proceeded to become more uniform during optimization; implying increased mechanical efficiency was achieved. The realistic simulated trabecular geometry suggests that the DSO method can accurately predict three-dimensional bone adaptation due to mechanical loading and that the proximal femur is an optimum structure as Wolff hypothesized. The secondary objective was to revise this computational framework to perform the first in-silico hip replacement considering micro-level bone remodeling. Two different commercially available hip prostheses were quantitatively analyzed using stress, strain energy, and bone mineral density as performance criteria and qualitatively visualized using the techniques above. Several important factors for stable fixation, determined from clinical evaluations, were evident: high levels of proximal bone loss, distal bone growth, and medial densification. The results suggest the DSO method can be utilized for comparative prosthetic implant stem design, uniquely considering post-operation bone remodeling as a design criterion. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2010-08-16 15:30:55.144

The work presented in this thesis has two distinct parts: (i) development of a spinal motion measurement technique and (ii) incorporation of the spinal motion measurement with galvanic vestibular stimulation (GVS) technology, acting as a balance assist device hereafter referred to as a galvanic vestibular stimulation device (GVSD). The developed spinal motion measurement technique fulfills seven desired attributes: accuracy, portability, real-time data capture of dynamic data, non-invasive, small device footprint, clinically useful and of non-prohibitive cost. Applications of the proposed system range from diagnosis of spine injury to postural and balance monitoring, on-field as well as in the lab setting. The system is comprised of three inertial measurement sensors, respectively attached and calibrated to the head, torso and hips, based on the subject’s anatomical planes. Sensor output is transformed into meaningful clinical parameters of rotation, flexion-extension and lateral bending of each body segment with respect to a global reference space, then collected and visualized via an interactive graphical user interface (GUI). The accuracy of the proposed sensing system has been successfully verified with subject trials using a VICON optical motion measurement system. Next, the proposed motion measurement system and technique has been used to record a standing iv subject’s motion response to GVS. The data obtained allows the development of a new GVSD with the attributes of: eligibility for commercial licensing, portability, and capable of safely providing controlled stimulating current to the mastoid bones at varying levels and frequencies. The successful combination of the spinal motion measurement technique and GVSD represents the preliminary stage of a balance prosthesis.