京都大学 / 新制・課程博士 / 博士(人間健康科学) / 甲第24541号 / 人健博第112号 / 新制||人健||8(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 黒木 裕士, 教授 青山 朋樹, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Purpose: To explore perceptions and initial outcomes of patients with rotator cuff-related pain to a pain education session. Materials and Methods: Ten individuals with persistent rotator cuff-related pain (≥3 months duration) attended an individual pain education session. They completed patient-reported outcomes measures on a weekly basis, three weeks prior and three weeks following the session. Individual semi-structured interviews were conducted three weeks following the pain education. Interviews were recorded, transcribed verbatim, and analyzed using the General Inductive Approach. Results: There were two over-arching key themes: firstly, ‘Participants’ Perspectives’ of the session generated four themes: Improved understanding of ‘the whole’; Mindful self-awareness; Taking charge; “The pain is still there”. Their understanding of pain was reconceptualised, evident by their ability to describe the role of neurophysiological mechanisms, stress and general well-being towards their pain. The second over-arching key theme, ‘Participants’ Recommendations’, had two themes: Integrating neuroscience with pathoanatomical knowledge and Educating other health professionals. Pain levels decreased post-pain education compared to pre-pain education. Conclusions: Following the pain education session, participants had greater understanding of factors influencing their shoulder pain. Pain education, in addition to pathoanatomical information may be useful as part of treatment for persistent rotator cuff-related pain.

No description available.

The glenohumeral (GH) joint is the most mobile joint in the human body, but its mobility inherently increases the risk of instability. The humeral head sits in a shallow glenoid in the scapula like a golf ball sitting on a tee. The stability in this joint is provided by the rotator cuff muscles and tendons that actively pull the humerus back into the socket to prevent dislocation, especially during overhead motions. However, the rotator cuff is prone to tears, resulting in pain, loss of mobility, and recreational limitations. Surgical reattachment of the tendon to the bone is challenging due to the mechanical disparity between the two tissues, resulting in stress concentrations and a high risk of retear. Notably, the specialized tissue at the tendon-to-bone attachment, which facilitates stress transfer between tendon and bone in healthy joints, does not regenerate after surgical reattachment and healing, making tendon-to-bone repairs prone to re-tears. A comprehensive understanding of GH joint biomechanics is essential for developing early interventions to prevent rotator cuff injuries. Furthermore, improving tendon-to-bone fixation during rotator cuff repair is critical to improve post-surgery outcomes. In the last decade, bioinspired solutions have shown considerable promise for addressing several biomedical problems. This thesis draws bioinspiration from two animals that have evolved unique mechanical functions: (i) the bat shoulder joint, which facilitates repetitive overhead motions during flight and may offer insights into rotator cuff pathology and (ii) the curvature of python snake teeth, which enables secure grasping of prey without soft tissue tearing. In the first part of the thesis, the bat shoulder was studied for its unique characteristics relative to mice. Overhead motions in humans often lead to shoulder injuries, partly because the bony anatomy of the unstable GH joint places greater stress on the joint's surrounding soft tissues to stabilize these motions. Traditional animal models used to study shoulder pathology are quadrupeds, which lack the capacity for overhead motion. In contrast, bats consistently engage in overhead motion during flight, subjecting their shoulders to substantial loading throughout their relatively long lifespan. Remarkably, the biomechanical demands placed on a bat's shoulder are estimated to exceed those of a competitive swimmer’s by 45-fold, despite sharing similar coracoacromial arch anatomy with humans. We were inspired to study functional adaptations in the shoulders of bats that enable this overhead motion. We performed comparative anatomy studies of the shoulders of bats and mice, similarly-sized quadrupeds. By quantifying the constraints imposed by the bony anatomy, we identified adaptations of the shoulder, including the rotator cuff tendons, that allow bats to sustain overhead motion in a high stress, repeated loading environment, without injury. In the second part of the thesis, python teeth were used as inspiration to develop a repair device optimized to grasp the rotator cuff without tearing. Rotator cuff repair surgeries fail frequently, with 20-94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we examined the specialized teeth of snakes of the Pythonoidea superfamily, which effectively grasp soft tissues without tearing. To apply this non-damaging and effective gripping approach to the surgical repair of tendons, we developed and optimized a python-tooth inspired array as an adjunct to current rotator cuff suture repair, and found that it nearly doubled repair strength. Integrated simulations, 3D printing, and ex vivo experiments revealed a relationship between tooth shape and grasping mechanics, and enabled optimization of a tooth array device to enhance rotator cuff repair to distribute stresses and increase tendon-bone contact. The efficacy of the approach was demonstrated via human cadaver tests, suggesting an alternative to traditional suturing paradigms that may reduce tendon re-tearing. Collectively, these studies contribute to a better understanding of the biomechanics of the GH joint and offer novel, bioinspired approaches for rotator cuff repair. The functional adaptations of bats provide insight into developing new approaches to treat GH joint instability, and a clinically relevant python-tooth inspired device can ultimately reduce the high rates of re-rupture currently observed in rotator cuff repair.

Current return-to-drive recommendations for patients following rotator cuff repair (RCR) surgery are not uniform due to a lack of empirical evidence relating driving safety and time-after-surgery. To address the limitations of previous work, Badger et al. (2022) evaluated, on public roads, the driving fitness of patients prior to RCR and at multiple post-operative timepoints. The goal of the Badger, et al. study was to make evidence-based return-to-drive recommendations in an environment with higher fidelity than that of a simulator and not subject to biases inherent to surveys. Badger et al., however, do not fully investigate the driving practices exhibited by subjects, overlooking the potential presence of compensatory driver behaviors. Further investigation of these behaviors through observation of direct driving techniques and practices over time can specifically answer how drivers may modify their behaviors to address a perceived state of impairment. Additionally, the degree of success in vehicle operation by comparing an ideal turn to the path taken by the driver allows for a level of quantification of the effectiveness of the compensatory techniques. Moreover, driver trajectories inferred from the vehicle Controller Area Network (CAN) metrics and from global positioning system (GPS) coordinates are contrasted with the ideal turn to assess minimum requirements for future sensors that are used to make these trajectory comparisons. This investigation leverages pre-existing data collected by the Virginia Tech Transportation Institute (VTTI) and Carilion Clinic as used in the analysis performed by Badger et al. (2022). RCR patients (n=27) executed the same prescribed driving maneuvers and drove the same route in a preoperative state and at 2-, 4-, 6-, and 12-weeks post operation. Behavioral data were annotated to extract key characteristics of interest and related them to relevant vehicle sensor readings. To construct vehicle paths, data was obtained from the on-board data acquisition system (DAS). Behavioral metrics considered the use of ipsilateral vehicle controls, performance of non-primary vehicle tasks, and steering techniques utilized to assess the impact of mobility restrictions due to sling use. Sling use was found to be a significant factor in use of the non-ipsilateral hand associated with the operative extremity (i.e., operative hand) on vehicle functions and, in particular, difficulty with the gear shifting control. Additionally, when considering the performance of non-primary vehicle tasks as assessed through a prescribed visor manipulation, sling use was not a significant factor for the task duration or completion of the task in a fluid motion. Sling use was, however, significant with respect to operative hand position prior to the completion of the visor manipulation: the operative hand was often not on the steering wheel prior to the visor maneuver. In addition, the operative hand was never used to manipulate the visor when the sling was worn. One-handed steering was also more frequent with the presence of the sling. Further behavioral analysis assessed the presence of compensatory behavior exhibited by subjects during periods in which impairment was perceived. Perceived impairment was observed as a function of the different experimental timepoints. Findings indicated a significant decrease in the lateral vehicle jerk during post-operative weeks 6 and 12. Significant differences, however, were not observed in body position alteration to avoid contact with the interior vehicle cabin, in over-the-shoulder checks, and in forward leans during yield and merge maneuvers. Regarding trajectory analysis, sling use did not produce a significant difference in the error metrics between the actual and ideal paths. In completion of turning maneuvers, however, operative extremity was significant for left turns, with greater error against the ideal path observed from those in the left operative cohort compared to those in the right operative cohort. For the right turn, however, operative extremity was not found to be a significant factor. In addition, the GPS data accuracy proved insufficient to support comparison against the ideal path. Overall, findings from this study provide metrics beyond those used in Badger, et al. that can be used in answering when it is safe for rotator cuff repair patients to return-to-drive. With the limited differences observed as a function of study timepoint and sling use, it is recommended that patients are able to safely return-to-drive at two weeks post-operation. If anything, results suggest that overcompensation, as inferred from observation of safer driving behaviors than normal, is present during some experimental timepoints, particularly post-operative week 2. / Master of Science / Current recommendations based on when it is safe for rotator cuff repair patients to return-to-drive are not standard because of a lack of suitable evidence. Previous work and recommendations rely on surveys and simulators which do not create fully realistic conditions and are subject to biases. To address the limitations of previous work, Badger et. al (2022) studied actual rotator cuff repair patients on public roads prior and following operation at multiple timepoints. Badger et al., however, did not consider the potential adaptations in driver behavior due to mobility restrictions and the perception of inferiority due to injury. Additionally, the degree of success of the adaptive driving behaviors based on the error between the actual vehicle path taken and a defined ideal path have not been explored in conjunction with the injury. This investigation is based on the pre-existing data collected by the Virginia Tech Transportation Institute (VTTI) and Carilion Clinic as used in the analysis performed by Badger et al. (2022). RCR patients (n=27) executed identical driving maneuvers and drove the same route before operation and at 2-, 4-, 6-, and 12-weeks post operation. Behavioral observations were recorded and related to relevant vehicle sensor readings. To construct vehicle paths, data was taken from the on-board data acquisition system (DAS). Participants adopted different behaviors, such as using the right hand to use the turn signal when the left arm was in a sling and the left hand to operate the gear shifter when the right arm was on a sling, to assist in combating mobility restrictions. One-handed steering was also more prominent during periods of sling-use. Sling-use, however, did not produce a significant difference in error between the actual vehicle path taken and the ideal path available to the driver. For left-operated participants completing left turns, there was also greater error in comparison to the ideal path than for the group of right-operated patients. However, there was not a difference between left- and right-operated arm participant error in completion of a right turn. The GPS data did not provide a suitable approximation of vehicle trajectory. Overall, findings from this study help to answer when it is safe for rotator cuff repair patients to return-to-drive through evaluation of the effectiveness of compensatory behaviors adopted by participants. With no significant difference in turn execution based on sling use, results suggest that patients can safely return-to-drive at two weeks post-operation. In fact, results suggest that overcompensation towards safer behaviors is present during some experimental timepoints, particularly post-operative week 2.

No description available.

No description available.

Surgical repair of torn rotator cuff tendons have a high rate of failure and does not address the underlying pathophysiology. Tissue engineering strategies, employing the use of multipotent progenitor cells or growth factors, represent potential therapies to improve the outcome of rotator cuff surgery. The use of glycosaminoglycan-based biomaterials in these therapies may enhance the effectiveness of cell and growth factor delivery techniques. Furthermore, understanding the cellular and molecular mediators in tendon overuse can help elucidate the causes of tendon degeneration. Thus the overall goals of this dissertation were to 1) develop heparin-based biomaterials to enhance cell pre-culture and maintain growth factor bioactivity and 2) characterize the histological and enzymatic changes in a supraspinatus tendon overuse model. To investigate the use of heparin in enhancing dynamic signaling, mesenchymal stem cells (MSCs) were encapsulated in heparin-containing hydrogels and evaluated for differentiation markers when cocultured with a small population of differentiated cells. To probe the effect of sulfation of heparin on the interactions with protein, selectively desulfated heparin species were synthesized and evaluated for their ability to bind and protect proteins. Finally, to develop a tendon overuse model that can become a test bed for testing future targeted therapeutics, an animal model was evaluated for tissue damage and protease activity. Together these studies represent a multi-pronged approach to understanding how tendon tissues become degenerative and for developing technologies to improve the biological fixation of tendon to bone in order to reduce the need for revision surgeries.

La stimulation électrique neurale, appliquée au système nerveux périphérique pour la restauration des fonctions motrices ou la neuromodulation, est une technologie en plein essor, en particulier la stimulation implantée avec des électrodes Cuff positionnées autour d’un nerf périphérique. Le principal frein au développement des systèmes de stimulation est la difficulté à obtenir la stimulation ou l’inhibition des fonctions cibles de manière précise et indépendante, c’est-à-dire, obtenir une sélectivité des fonctions. Les paramètres impliqués dans la sélectivité au sens large ne sont pas toujours intuitifs, et le nombre de degrés de libertés (choix de l’électrode, nombre de contacts, forme du pulse etc.) est important. Tester toutes ces hypothèses en expérimentation n’est pas faisable et inenvisageable dans le réglage des neuroprothèses en contexte clinique. La modélisation a priori nous permet d’établir des critères de choix, de déterminer les stratégies les plus efficaces et de les optimiser. Par ailleurs, un grand nombre d’études ont pu prévoir des stratégies de sélectivité inédites grâce à la modélisation, et validées a posteriori par l’expérimentation. Le schéma de calcul scientifique est composé de deux parties. On modélise, d’une part, la propagation du champ de potentiels électriques générés par les électrodes à l’intérieur d’un volume conducteur représentant le nerf (étude biophysique), et d’autre part l’interaction entre ce champ de potentiels et les neurones (réponse électrophysiologique). Notre première contribution propose une méthode originale de modélisation et d’optimisation de la sélectivité spatiale avec une électrode Cuff, sans connaissance a priori de la topographie de nerf. Partant de ce constat, nous déterminons de nouveaux critères, l’efficacité et la robustesse, complémentaires à la sélectivité, nous permettant de faire un choix entre des configurations multipolaires concurrentes. Ainsi, en fonction de la pondération de ces critères, nous avons développé un algorithme d’optimisation pour déterminer la configuration optimale en fonction de la zone choisie, du diamètre des fibres visées ainsi que de la durée de stimulation, pour un pulse type rectangulaire de référence. Des expérimentations sur modèle animal nous ont permis d’évaluer l’efficacité de la méthode et sa généricité. Ce travail est partie intégrante d’un projet plus vaste de stimulation du nerf vague (projet INTENSE), où l’une des applications concerne le traitement des troubles cardiaques. L’objectif est d’activer sélectivement une population spécifique de fibres nerveuses pour obtenir des effets plus ciblés conduisant à une thérapie améliorée, tout en diminuant les effets secondaires. La deuxième contribution consiste à combiner la sélectivité spatiale et la sélectivité au diamètre de fibre avec un modèle générique de nerf et une électrode Cuff à 12 contacts. L’utilisation d’une forme d’onde particulière (prépulse) combinée avec des configurations multipolaires permet d’activer des fibres d’un diamètre défini dans un espace ciblé. Les perspectives cliniques sont nombreuses, notamment sur la réduction de la fatigue liée à l’utilisation prolongée de la stimulation ou la diminution des effets secondaires. Dans le cadre du projet INTENSE, la seconde application liée à la stimulation du nerf vague vise le problème de l’obésité morbide. L’activation des axones cibles liés aux fonctions gastriques nécessite une quantité de charges conséquente. Plusieurs études suggèrent que les formes de pulse non rectangulaires peuvent activer les axones du système nerveux périphérique avec une quantité de charges réduite comparée à la forme de pulse rectangulaire de référence. Notre dernière contribution concerne l’étude expérimentale et de modélisation de ces formes d’ondes complexes. L’approche par modélisation, si elle est bien maîtrisée, apporte une analyse pertinente voire même indispensable au réglage clinique des neuroprothèses. / Neural electrical stimulation, applied to the peripheral nervous system for motor functions restoration or neuromodulation, is a thriving technology, especially implanted stimulation using Cuff electrodes positioned around a peripheral nerve. The main obstacle to the development of stimulation systems is the difficulty in obtaining the independent stimulation or inhibition of specific target functions (i.e. functional selectivity). The parameters involved in selectivity are not always intuitive and the number of degrees of freedom (choice of electrode, number of contacts, pulse shape etc.) is substantial. Thus, testing all these hypotheses in a clinical context is not conceivable. This choice of parameters can be guided using prior numerical simulations predicting the effect of electrical stimulation on the neural tissue. Numerous studies developed new strategies to achieve selectivity based on modeling results that have been validated a posteriori by experimental works. The computation scheme is composed of two parts : the modeling of the potential field generated by the electrodes inside a conductive medium representing the nerve on the one hand; and the determination of the interaction between this field of potentials and neurons on the other. Our first contribution is an original method of modeling and optimization of the spatial selectivity with a Cuff electrode, without prior knowledge of the nerve topography. Based on this observation, we determined new criteria, efficiency and robustness, complementary to selectivity, allowing us to choose between multipolar configurations. Thus, according to the weighting applied to these criteria, we developed an optimization algorithm to determine the optimal configuration as a function of the target zone, fiber diameter and the stimulation duration for a typical rectangular pulse. Experiments on animal model allowed us to evaluate the effectiveness and genericness of the method. This work was performed as part of a larger project on vagus nerve stimulation (INTENSE project) in which one of the applications focused on the treatment of cardiac disorders. The main objective was to selectively activate a specific population of nerve fibers to improve therapy and decrease side effects. In a second contribution, numerical simulations were used to investigate the combination of multipolar configurations and the prepulses technique, in order to obtain fiber recruitment in a spatially reverse order. The main objective was to achieve both spatial and fiber diameter selectivity. Expected clinical perspectives of this work are the reduction of fatigue related to a prolonged use of stimulation and the reduction of side effects. Within the framework of the INTENSE project, the second application investigated vagus nerve stimulation as a therapy for morbid obesity. Activation of target axons related to gastric functions requires a significant amount of charge injection. Several studies suggest that non-rectangular waveforms can activate axons of the peripheral nervous system with a reduced amount of charge compared to the reference rectangular pulse shape. Our last contribution focuses on the experimental study and the modeling of these complex waveforms. The modeling approach, if performed properly and while bearing in mind its limits, provides a relevant and even indispensable analysis tool for the clinical adjustment of neuroprostheses.

Rotator cuff disease is multi-factored and has been attributed to both intrinsic and extrinsic factors. Extrinsic factors contribute to compression of the rotator cuff tendons. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. Subacromial impingement is related to factors that encroach upon the subacromial space, while internal impingement affects the articular side of the tendons adjacent to glenoid. While the mechanisms of impingement are varied, further research is necessary to improve treatment and patient outcomes. Chapter 2 is a thorough review of literature on the mechanisms of rotator cuff disease. Alterations in scapular kinematics may influence subacromial space and either contribute to the etiology of subacromial impingement with rotator cuff tendon compression or serve as a compensation to alleviate compression. Furthermore alterations in scapular position may directly influence rotator cuff muscle strength. Chapter 3 compares the influence of the scapular assistance test on scapular upward rotation, posterior tilt, subacromial space, and shoulder strength between healthy individuals and subjects with subacromial impingement syndrome. Scapular upward rotation and posterior tilt induced with scapular assistance test appears to influence subacromial space, but not shoulder muscle strength; however, the influence of these scapular rotations do not differ between asymptomatic individuals and those with subacromial impingement. Furthermore scapular posterior tilt appears to have a greater influence on increasing subacromial space and should be emphasized in the treatment of individuals with subacromial impingement. In chapter 4, we examine the influence that obvious scapular dyskinesis and passive scapular correction with the scapular assistance test have on 3D scapular kinematics and subacromial space. Scapular dyskinesis did not alter scapular kinematics or acromiohumeral distance during active elevation in static positions, in the scapular plane, and without a load when compared to those without scapular dyskinesis. This suggests other contributing factors, such as pain, increased load, or fatigue is requisite to alterations in scapular kinematics or AHD. Passive correction with the scapular assistance test increased scapular upward rotation, posterior tilt, and subacromial space in individuals with and without dyskinesis. In patients with obvious dyskinesis, there was a greater increase in scapular upward rotation with passive scapular assistance. This increased scapular upward rotation had a negative relationship with change in the acromiohumeral distance. The scapular dyskinesis test increased acromiohumeral distance and therefore may be helpful identifying individuals where subacromial compression is producing symptoms, regardless of dyskinesis. The results of this research suggest scapular kinematics and subacromial space are altered with the passive maneuver of the scapular assistance test in all individuals, regardless of subacromial impingement syndrome or scapular dyskinesis. Scapular dyskinesis alone may not be detrimental to scapular position and subacromial space when evaluated in static positions of active arm elevation. Other potential factors may be required to alter scapular kinematics to reduce subacromial space including pain, dynamic movement, load or fatigue. Further study is necessary to determine the influence of the combination of these factors in individuals with scapular dyskinesis.