Physically-based Muscles and Fibers Modeling from Superficial Patches.

We propose a novel approach for the generation of volumetric muscle primitives and their associated fiber field, suitable for simulation in computer animation. Muscles are notoriously difficult to sculpt because of their complex shapes and fiber architecture, therefore often requiring trained artists to render anatomical details. Moreover, physics simulation requires these geometries to be modeled in an intersection-free rest state and to have a spatially-varying fiber field to support contraction with anisotropic material models. Inspired by the principles of computational design, we satisfy these requirements by generating muscle primitives automatically, complete with tendons and fiber fields, using physics based simulation of inflatable 3D patches which are user-defined on the external mesh of a character

Surface Electromyographic (sEMG) Transduction of Hand Joint Angles for Human Interfacing Devices (HID)

This is an investigation of the use of surface electromyography (sEMG) as a tool to improve human interfacing devices (HID) information bandwidth through the transduction of the fingertip workspace. It combines the work of Merletti et al and Jarque-Bou et al to design an open-source framework for Fingertip Workspace based Human Interfacing Devices (HID). In this framework, the fingertip workspace is defined as the system of forearm and hand muscle force through a tensor which describes hand anthropometry. The thesis discusses the electrophysiology of muscle tissue along with the anatomy and physiology of the arm in pursuit of optimizing sensor location, muscle force measurements, and viable command gestures. Algorithms for correlating sEMG to hand joint angle are investigated using MATLAB for both static and moving gestures. Seven sEMG spots and Fingertip Joint Angles recorded by Jarque Bou et al are investigated for the application of sEMG to Human Interfacing Devices (HID). Such technology is termed Gesture Computer Interfacing (GCI) and has been shown feasible through devices such as CTRL Labs interface, and models such as those of Sartori, Merletti, and Zhao. Muscles under sEMG spots in this dataset and the actions related to them are discussed, along with what muscles and hand actions are not visible within this dataset. Viable gestures for detection algorithms are discussed based on the muscles discerned to be visible in the dataset through intensity, spectral moment, power spectra, and coherence. Detection and isolation of such viable actions is fundamental to designing an EMG driven musculoskeletal model of the hand needed to facilitate GCI. Enveloping, spectral moment, power spectrum, and coherence analysis are applied to a Sollerman Hand Function Test sEMG dataset of twenty-two subjects performing 26 activities of living to differentiate pinching and grasping tasks. Pinches and grasps were found to cause very different activation patterns in sEMG spot 3 relating to flexion of digits I - V. Spectral moment was found to be less correlated with differentiation and provided information about the degree of object manipulation performed and extent of fatigue during each task. Coherence was shown to increase between flexors and extensors with intensity of task but was found corrupted by crosstalk with increasing intensity of muscular activation. Some spectral results correlated between finger flexor and extensor power spectra showed anticipatory coherence between the muscle groups at the end of object manipulation. An sEMG amplification system capable of capturing HD-sEMG with a bandwidth of 300 and 500 Hz at a sampling frequency of 2 kHz was designed for future work. The system was designed in ordinance with current IEEE research on sensor-electrode characteristics. Furthermore, discussion of solutions to open issues in HD-sEMG is provided. This work did not implement the designed wristband but serves as a literature review and open-source design using commercially available technologies

Physics-based modelling, simulation, placement and learning for musculo-skeletal animations.

In character production for Visual Effects, the realism of deformations and flesh dynamics is a vital ingredient of the final rendered moving images shown on screen. This work is a collection of projects completed at the hosting company MPC London focused on the main components needed for the animation of musculo-skeletal systems: primitives modeling, physically accurate simulation, interactive placement. Complementary projects are also presented, including the procedural modeling of wrinkles and a machine learning approach for deformable objects based on Deep Neural Networks. Primitives modeling aims at proposing an approach to generating muscle geometry complete with tendons and fibers from superficial patches sketched on the character skin mesh. The method utilizes the physics of inflatable surfaces and produces meshes ready to be tetrahedralized, that is without compenetrations. A framework for the simulation of muscles, fascia and fat tissues based on the Finite Elements Method (FEM) is presented, together with the theoretical foundations of fiber-based materials with activations and their fitting in the Implicit Euler integration. The FEM solver is then simplified in or- der to achieve interactive rates to show the potential of interactive muscle placement on the skeleton to facilitate the creation of intersection-free primitives using collision detection and resolution. Alongside physics simulation for biological tissues, the thesis explores an approach that extends the Implicit Skinning technique with wrinkles based on convolution surfaces by exploiting the gradients of the combination of bones fields. Finally, this work discusses a possible approach to the learning of physics-based deformable objects based on deep neural networks which makes use of geodesic disks convolutional layers

New screening methodology for selection of polymeric materials for transdermal drug delivery devices

As medical advances extend the human lifespan, the level of chronic illnesses will increase and thus straining the needs of the health care system that, as a result, governments will need to balance expenses without upsetting national budgets. Therefore, the selection of a precise and affordable drug delivery technology is seen as the most practical solution for governments, health care professionals, and consumers. Transdermal drug delivery patches (TDDP) are one of the best economical technologies that are favored by pharmaceutical companies and physicians alike because it offers fewer complications when compared to other delivery technologies. TDDP provides increased efficiency, safety and convenience for the patient. The TDDP segment within the US and Global drug delivery markets were valued at $5.6 and$12.7 billion respectively in 2009. TDDP is forecasted to reach $31.5 billion in 2015. The present TDDP technology involves the fabrication of a patch that consists of a drug embedded in a polymeric matrix. The diffusion coefficient is determined from the slope of the cumulative drug release versus time. It is a trial and error method that is time and labor consuming. With all the advantages that TDDPs can offer, the methodology used to achieve the so-called optimum design has resulted in several incidents where the safety and design have been put to question in recent times (e.g. Fentanyl). A more logical screening methodology is needed. This work shows the use of a modified Duda Zielinsky equation (DZE). Experimental release curves from commercial are evaluated. The experimental and theoretical Diffusion Coefficient values are found to be within the limits specified in the patent literature. One interesting finding is that the accuracy of the DZE is closer to experimental values when the type of Molecular Shape and Radius are used. This work shows that the modified DZE could be used as an excellent screening tool to determine the optimal polymeric matrices that will yield the desired Diffusion Coefficient and thus effectively decreasing the amount of time and labor when developing TDDPs

Distributed Sensing and Stimulation Systems Towards Sense of Touch Restoration in Prosthetics

Modern prostheses aim at restoring the functional and aesthetic characteristics of the lost limb. To foster prosthesis embodiment and functionality, it is necessary to restitute both volitional control and sensory feedback. Contemporary feedback interfaces presented in research use few sensors and stimulation units to feedback at most two discrete feedback variables (e.g. grasping force and aperture), whereas the human sense of touch relies on a distributed network of mechanoreceptors providing high-fidelity spatial information. To provide this type of feedback in prosthetics, it is necessary to sense tactile information from artificial skin placed on the prosthesis and transmit tactile feedback above the amputation in order to map the interaction between the prosthesis and the environment. This thesis proposes the integration of distributed sensing systems (e-skin) to acquire tactile sensation, and non-invasive multichannel electrotactile feedback and virtual reality to deliver high-bandwidth information to the user. Its core focus addresses the development and testing of close-loop sensory feedback human-machine interface, based on the latest distributed sensing and stimulation techniques for restoring the sense of touch in prosthetics. To this end, the thesis is comprised of two introductory chapters that describe the state of art in the field, the objectives and the used methodology and contributions; as well as three studies distributed over stimulation system level and sensing system level. The first study presents the development of close-loop compensatory tracking system to evaluate the usability and effectiveness of electrotactile sensory feedback in enabling real-time close-loop control in prosthetics. It examines and compares the subject\u2019s adaptive performance and tolerance to random latencies while performing the dynamic control task (i.e. position control) and simultaneously receiving either visual feedback or electrotactile feedback for communicating the momentary tracking error. Moreover, it reported the minimum time delay needed for an abrupt impairment of users\u2019 performance. The experimental results have shown that electrotactile feedback performance is less prone to changes with longer delays. However, visual feedback drops faster than electrotactile with increased time delays. This is a good indication for the effectiveness of electrotactile feedback in enabling close- loop control in prosthetics, since some delays are inevitable. The second study describes the development of a novel non-invasive compact multichannel interface for electrotactile feedback, containing 24 pads electrode matrix, with fully programmable stimulation unit, that investigates the ability of able-bodied human subjects to localize the electrotactile stimulus delivered through the electrode matrix. Furthermore, it designed a novel dual parameter -modulation (interleaved frequency and intensity) and compared it to conventional stimulation (same frequency for all pads). In addition and for the first time, it compared the electrotactile stimulation to mechanical stimulation. More, it exposes the integration of virtual prosthesis with the developed system in order to achieve better user experience and object manipulation through mapping the acquired real-time collected tactile data and feedback it simultaneously to the user. The experimental results demonstrated that the proposed interleaved coding substantially improved the spatial localization compared to same-frequency stimulation. Furthermore, it showed that same-frequency stimulation was equivalent to mechanical stimulation, whereas the performance with dual-parameter modulation was significantly better. The third study presents the realization of a novel, flexible, screen- printed e-skin based on P(VDF-TrFE) piezoelectric polymers, that would cover the fingertips and the palm of the prosthetic hand (particularly the Michelangelo hand by Ottobock) and an assistive sensorized glove for stroke patients. Moreover, it developed a new validation methodology to examine the sensors behavior while being solicited. The characterization results showed compatibility between the expected (modeled) behavior of the electrical response of each sensor to measured mechanical (normal) force at the skin surface, which in turn proved the combination of both fabrication and assembly processes was successful. This paves the way to define a practical, simplified and reproducible characterization protocol for e-skin patches In conclusion, by adopting innovative methodologies in sensing and stimulation systems, this thesis advances the overall development of close-loop sensory feedback human-machine interface used for restoration of sense of touch in prosthetics. Moreover, this research could lead to high-bandwidth high-fidelity transmission of tactile information for modern dexterous prostheses that could ameliorate the end user experience and facilitate it acceptance in the daily life

Hernia Surgery

A hernia occurs when an internal organ pushes through a weak spot in the body’s muscle or tissue. There are several types of hernia, including inguinal hernias, femoral hernias, umbilical hernias, and hiatal hernias. Hernias usually do not get better on their own and surgery may be the only way to repair them. This book discusses different types of hernias and hernia surgeries, including open surgery, laparoscopic surgery, and robotic repair

Tendon injury and repair - A perspective on the basic mechanisms of tendon disease and future clinical therapy

Tendon is an intricately organized connective tissue that efficiently transfers muscle force to the bony skeleton. Its structure, function, and physiology reflect the extreme, repetitive mechanical stresses that tendon tissues bear. These mechanical demands also lie beneath high clinical rates of tendon disorders, and present daunting challenges for clinical treatment of these ailments. This article aims to provide perspective on the most urgent frontiers of tendon research and therapeutic development. We start by broadly introducing essential elements of current understanding about tendon structure, function, physiology, damage, and repair. We then introduce and describe a novel paradigm explaining tendon disease progression from initial accumulation of damage in the tendon core to eventual vascular recruitment from the surrounding synovial tissues. We conclude with a perspective on the important role that biomaterials will play in translating research discoveries to the patient.STATEMENT OF SIGNIFICANE: Tendon and ligament problems represent the most frequent musculoskeletal complaints for which patients seek medical attention. Current therapeutic options for addressing tendon disorders are often ineffective, and the need for improved understanding of tendon physiology is urgent. This perspective article summarizes essential elements of our current knowledge on tendon structure, function, physiology, damage, and repair. It also describes a novel framework to understand tendon physiology and pathophysiology that may be useful in pushing the field forward.</p

Electrospun Nanofibers as a Green Approach for the Development of Advanced Biomedical, Pharmaceutical, and Filter Materials

The present Thesis focuses on the fabrication of polysaccharide \u2013 based nanofibrous mats via electrospinning technique primarily for, but not limited to, the development of wound healing patches with enhanced tissue regeneration capabilities. Specifically, this project arose to overcome the lack of methodologies concerning the proficient electrospinning of polysaccharides due to their poor processability, the requirement of hazardous and/or toxic solvents, and nanofiber inadequate stability in aqueous environments. To tackle this task, this Thesis proposes the use of poly(ethylene oxide), a biocompatible and water \u2013 soluble synthetic polymer able to increase the polysaccharide \u2013 based formulation spinnability, along with a simple washing \u2013 physical crosslinking treatment to fabricate pure polysaccharide nanofibers with boosted water resistance and marked biocompatibility. In the first Chapters, after a general discussion concerning the technological relevance and versatility of electrospinning technique together with its main applications, this Thesis concentrates on briefly presenting the properties of polysaccharide materials and their advantages with respect to synthetic polymers, as well as the experimental methodologies and characterization approaches used to achieve the investigated purpose. Then, either alginate or chitosan polysaccharides are employed for the fabrication of nanofibrous mats, whose physical \u2013 chemical properties, drug delivery capabilities, and biological responses are fully characterized. As a matter of fact, the developed systems effectively display a significant capacity to promote cell adhesion and proliferation along with proper mechanical, water \u2013 related, and drug release features, hence representing promising materials to be used in several biomedical and pharmaceutical products. Finally, the preparation of a multilayer nanofibrous patch comprised of an external hydrophobic stratum and an internal bioactive one is explored and discussed. To this end, combining a polyurethane nanofibrous layer with an alginate nanofibrous layer enriched with ZnO nanoparticles allows the fabrication of potential wound healing patches endowed with superior support and protective performances. These results are an important first step in making straightforward the electrospinning of polysaccharide materials granting the possibility to easily prepare nanofibrous meshes with potential uses in various application fields, with particular relevance in the biomedical and pharmaceutical industries where the bioactivity of these materials with respect to synthetic polymers plays a topical role

Hybrid antibacterial microneedle patches against skin infections

Skin and soft tissue infections (SSTIs) are a major healthcare burden that has increased in incidence since the beginning of the 21st century resulting in an annual spending of approximately 15 b$ in 2012 in the United States (US).1 Treatment of SSTIs is complex and typically involves the administration of antibiotics. However, the antibiotic therapy of SSTIs has multiple obstacles interfering with an efficient treatment outcome such as (i) limited local antibiotic penetration into the skin and (ii) rising antibiotic resistant SSTIs. The limitation of local drug penetration is associated with the route of administration. On the one hand, antibiotics can be given topically; however, the protective function of the skin limits the types of drugs that can efficiently be given via this route. On the other hand, systemic administration of the antibiotic parenterally or intravenously (IV) shows low local skin absorption while suffering from side effects associated with the systemic exposure of the body to the antibiotic. Furthermore, the rise in antibiotic resistance urgently calls for the development of novel antibacterial treatment options to optimize the antibacterial effect of current antibiotics and reduce further resistance development. A potential to improve the antibacterial effect of antibiotics is through multimodal therapies and as such the incorporation of heat from photothermal therapy (PTT) has been reported as a promising avenue to improve antibiotic efficiency. In the scope of this thesis, microneedle (MN) arrays were developed to address the problems faced in the treatment of bacterial SSTIs. In the first part of this thesis, dissolvable MN arrays loaded with the antibiotic vancomycin (VAN) were developed and tested in ex vivo porcine infection models of methicillin-resistant Staphylococcus aureus (MRSA), a strain commonly found in SSTIs. The MN arrays allowed the delivery of high concentrations of VAN locally in the skin where it remained active to inhibit the growth of MRSA after only two applications for 10 minutes. The second part of this thesis describes the development of photothermal MN arrays with plasmonic Au/SiO2 and Ag/SiO2 nanoaggregates. Four different fabrication methods following traditional mold-and-casting methods using Au/SiO2 revealed that the rational selection of the fabrication method allows for a control over the MN morphology, photothermal effect, and a reduction of nanoparticle (NP) deposition into the skin. Additionally, Ag/SiO2 nanoaggregates were employed in nanocomposites of ultraviolet (UV)-curable resin to be used for the 3D printing of photothermal MN arrays. Such 3Dprinted photothermal MN arrays allowed for the in vitro killing of the SSTI-associated bacterial species S. aureus and Pseudomonas aeruginosa by heat. However, final temperature of the planktonic samples reached >60 ºC limiting the clinical potential of such photothermal MNs as monotherapies since such high temperatures may cause damage to healthy cells. Therefore, hybrid MN arrays were developed that incorporate both VAN and photothermal nanoaggregates to reduce the needed antibiotic and temperature dose through synergistic interactions. Such hybrid MNs were fabricated employing an outer, dissolvable, drug-loaded layer and an inner, non-dissolvable, photothermal core aiming to combine the advantages of (i) high local VAN delivery and (ii) intradermal PTT. We showed the successful synergistic growth inhibition of MRSA in vitro of such hybrid MN arrays. Overall, the work in this thesis introduces a potential novel treatment option for bacterial SSTIs

Postnatal ocular development in laboratory animals : a histological and immunohistochemical study

La vue est sans doute le plus important des sens. L'anatomie, l'histologie et la physiologie de l'œil normale chez les espèces de laboratoire adultes ont généralement été bien documentées. Cependant, les références décrivant les caractéristiques histomorphologiques du développement oculaire postnatal chez les animaux de laboratoire demeurent sporadiques et incomplètes. L'évaluation de tissus oculaires provenant d'animaux immatures peut être nécessaire lors d’études précliniques juvéniles de toxicité effectuées dans le but d’évaluer l'innocuité de médicaments destinés à la population pédiatrique. En effet, les données découlant d'études précliniques réalisées avec des animaux matures ne sont pas toujours jugées appropriées pour évaluer la toxicité d'un composé lorsqu'il est administré à des enfants. Cependant, la rareté des références histologiques sur le développement postnatal chez les animaux, ainsi que l'absence courante de témoins appariés selon l'âge pour les animaux sacrifiés de façon précoce lors d’études juvéniles, peuvent rendre difficile l'analyse des structures de l’œil en développement. Ainsi, l'objectif de cette thèse était de fournir des connaissances histologiques et immunohistochimiques (IHC) sur le développement oculaire postnatal, de la naissance au stade prépubère, chez le rat Sprague Dawley (SD), cochon domestique (DP), cochon miniature Göttingen (MP) et chien Beagle (BG). Les résultats de cette thèse ont démontré l'immaturité marquée de toutes les structures oculaires chez les rats SD et les chiens BG à la naissance et pendant la période postnatale. À la naissance, la rétine chez ces espèces altriciales était encore composée de la couche neuroblastique externe fœtale, et plusieurs étapes cruciales de la rétinogenèse, mises en évidence avec l’IHC, se sont produites lors des premières semaines de vie. D’autres évidences d'immaturité oculaire chez ces espèces incluaient la stratification de l’épithélium cornéen lors de l'ouverture des paupières et la présence de vestiges de la vascularisation hyaloïde. En revanche, les yeux des DP et MP, considérés comme une espèce précoce, étaient davantage développés à la naissance, néanmoins, d'importants changements de morphogenèse ont été observés lors de la période postnatale. Par exemple, la rétine du cochon néonatal présentait des photorécepteurs peu développés. Chez toutes les espèces examinées, la prolifération cellulaire et l'engagement des cellules dans le cycle cellulaire, mis en évidence avec Ki-67 et/ou PHH3, étaient prédominants dans la majorité des structures oculaires en développement. L'apoptose, démontrée avec l'IHC contre caspase-3 activé et/ou l'histochimie TUNEL, s’est avérée une caractéristique histologique clé à des âges précis de la rétinogenèse chez les rats SD et les chiens BG. Ce changement était aussi notable dans l'épithélium immature du cristallin du rat SD, ainsi que dans les vestiges hyaloïdes chez toutes les espèces. Enfin, des évidences d’activation non-apoptotique de caspase-3 ont été observées dans différents types cellulaires chez toutes les espèces. Les connaissances présentées dans cette thèse pourront servir de référence pour les pathologistes devant évaluer des structures oculaires en développement dans le cadre d'études précliniques de toxicité. Par ailleurs, les résultats de cette thèse ouvrent la voie pour des investigations plus approfondies sur le développement oculaire, particulièrement chez le chien et le cochon, qui pourront servir à des recherches futures en ophtalmologie pédiatrique.Vison is arguably the most important of senses. The normal anatomy, histology, and physiology of the eye in mature laboratory species have generally been well documented, particularly in rodents. However, references addressing the histomorphological features of the postnatal ocular development in laboratory animals, notably in nonprimate large animal models, remain sporadic and incomplete. From a veterinary toxicologic pathology perspective, the evaluation of ocular tissues from immature animals may be needed during different types of preclinical juvenile animal toxicity studies conducted to assess the safety of xenobiotics on the pediatric population. Data from preclinical studies conducted in mature animals are often not deemed appropriate to evaluate the toxicity of a drug when administered to children, thus warranting the need to use juvenile animals. However, the paucity of histological references describing the postnatal development of laboratory animals, along with the common lack of age-matched controls when animals are unexpectedly sacrificed (or found death) early during juvenile studies, can render the analysis of developing ocular structures challenging. Thus, the objective of this thesis was to provide comprehensive histological and immunohistochemical (IHC) knowledge on the postnatal ocular development, using several age timepoints from birth to the peripubertal stage, in the Sprague Dawley (SD) rat, domestic pig (DP), Göttingen minipig (MP) and Beagle (BG) dog. Overall, the results from this thesis demonstrated the marked immaturity of all ocular structures in SD rats and BG dogs at birth and during the postnatal period. Notably, the retina at birth in these altricial species still contained the highly proliferative fetal outer neuroblastic layer, and critical retinogenesis events, highlighted with IHC, occurred rapidly during the first few weeks of life. Other noteworthy features of ocular immaturity in these species included the corneal epithelial stratification happening around the time of eyelid opening, the presence of hyaloid vascular remnants, and the globally poorly developed eye anterior segment. Contrastingly, the eyes of the DP and MP, considered a precocial species, were appreciably more developed at birth, although important ocular morphogenesis changes still occurred after birth. Importantly, the neonatal pig retina presented poorly developed cone and rod photoreceptors. In all examined species, cellular proliferation and the engagement of cells in the cell cycle, highlighted by Ki-67 and/or PHH3 IHC, were prominent in nearly all developing ocular structures for variable periods of time. Physiologically occurring apoptosis, highlighted by cleaved-caspase-3 IHC and/or TUNEL histochemistry, was a key histological feature of retinogenesis at specific age timepoints in SD rats and BG dogs, and was notable in the SD rat immature lens epithelium, as well as in regressing hyaloid vasculature remnants of all species. Lastly, evidence of nonapoptotic activation of caspase-3 was observed in different ocular cell types in all species. The information presented in this thesis will hopefully serve as general reference material for pathologists evaluating immature ocular structures in the context of preclinical toxicity studies. Moreover, the results pave the way for more in-depth investigations of specific ocular developmental events in nonprimate large animal models that may be useful for pediatric ophthalmology translational research