Tendons transfer forces from muscle to bone and allow the locomotion of the body. However, tendons, especially for tendons in the hand, get lacerated commonly in different injuries and the healing of tendon within the narrow channel in the hand will normally lead to tendon adhesion and sacrificed tendon mechanics. Researches have been focused on addressing tendon adhesion prevention but neglecting healed tendon mechanics. This thesis discusses the principles and challenges in the design of biomaterials regarding flexor tendon repair with advanced polymer chemistry and materials science. A rational platform, not only focusing on the prevention of tendon adhesion, but devoting more efforts on final healed properties of tendons via implementing glycopolymer-based materials to guide tendon cells attachment, was designed, fabricated and characterized. Controlled ring opening polymerizations and atom transfer radical polymerizations were combined for the synthesis of miktoarm well-defined block copolymers. Para-fluorine click reactions were then implemented to afford glycopolymers with glucose units. Obtained copolymers were transformed into 3D membranes constituting a porous fibrous structure utilizing electrospinning. The aligned structure was then fabricated to optimize the mechanics of these materials for practical application as well as reconstruct normal tendon physiological structure. Lastly, the toxicity, cell affinity and cell activity of obtained materials were evaluated in vitro employing tendon cells as a cell line to confirm the suitability of obtained platforms for flexor tendon repair.

The tibialis anterior (TA) muscle plays a vital role in human movement such as walking and running. Overuse of TA during these movements leads to an increased susceptibility of injuries e.g. chronic exertional compartment syndrome. TA activation has been shown to be affected by increases in exercise, age, and the external environment (i.e. incline and footwear). Because activation parameters of TA change with condition, it leads to the interpretation that force changes occur too. However,activation is only an approximate indicator of force output of a muscle. Therefore, the overall aim of this thesis was to investigate the parameters affecting accurate measure of TA force, leading to development of a subject-specific EMG-driven model, which takes into consideration specific methodological issues. The first study investigated the reasons why the tendon excursion and geometric method differ so vastly in terms of estimation of TA moment arm. Tendon length changes during the tendon excursion method, and location of the TA line of action and irregularities between talus and foot rotations during the geometric method, were found to affect the accuracy of TA moment arm measurement. A novel, more valid, method was proposed. The second study investigated the errors associated with methods used to account for plantar flexor antagonist co-contraction. A new approach was presented and shown to be, at worse, equivalent to current methods, but allows for accounting throughout the complete range of motion. The final study utilised the outputs from studies one and two to directly measure TA force in vivo. This was used to develop, and validate, an EMG-driven TA force model. Less error was found in the accuracy of estimating TA force when the contractile component length changes were modelled using the ankle, as opposed to the muscle. Overall, these findings increase our understanding of not only the mechanics associated with TA and the ankle, but also improves our ability to accurately monitor these.

Tendon disorders are painful, disabling, and a major healthcare problem, with millions of people affected by tendon injuries each year. Current treatment strategies are inadequate and knowledge of the underlying mechanobiological mechanisms is required to develop novel therapies. Although the tissue–level properties of tendon are well–documented there remains a lack of understanding of the deformation mechanisms of this complex tissue. Therefore, the aim of this thesis is to characterize the microstructural deformation of tendon through biological imaging, mechanical testing, and computational modeling. Emphasis is placed on the structure and function of elastic fibers in tendon, whose role is poorly understood. First, histology, immunohistochemistry, and multiphoton microscopy are used to characterize the organization of elastic fibers in healthy and damaged tendon providing detailed microstructural information on their morphology and location for the first time. Elastic fibers are found to have a sparse distribution in the extracellular matrix, but are highly concentrated in the endotenon sheath and pericellular matrix. Moreover, damaged specimens are found to have a severely disrupted elastic fiber network. Elastic fibers likely contribute to fascicular deformation mechanisms and the micromechanical environment of tenocytes, which are expected to be disrupted in damaged tendon. Second, mechanical testing and enzyme treatments are used to analyze the mechanical contribution of elastic fibers to tendon. Elastase is found to significantly affect the mechanical properties of the tissue and remove the elastin component of both tendon and a control collagen–elastin biomaterial. However, elastase is also found to degrade non–elastin structural molecules that may contribute to tendon mechanics. The mechanical changes associated with the elastase treatment suggest that elastic fibers do not contribute to the elastic recoil of tendon as previously hypothesized. Third, multiphoton microscopy in combination with a novel microtensile testing machine is used to observe the deformation of collagen fibrils and tenocytes in tissue exposed to load. Tissue displacement is consistent with a helical arrangement of fibrils and nuclei experience significant elongation under physiological conditions. These results suggest that a helical arrangement of fibrils is responsible for the nonlinear stress–strain response of tendon and that nuclei are prime candidates for sensing mechanical forces in tendon. Finally, computation modeling and structural imaging are used to generate a microstructural finite element model of tendon. A helical model with embedded pericellular matrix is able to reproduce the stress–strain response and cell–level deformation of the tissue. The pericellular matrix is found to amplify mechanical forces exposed to cells, which is required to initiate mechanobiological stimulation of tenocytes under physiological conditions. Therefore, the structure and composition of the PCM during health and disease is expected to significantly affect mechanobiological mechanisms of tendon. The work presented in this thesis has used new experimental methods to provide novel insight into the structure, function, and deformation mechanisms of tendon. The techniques and concepts developed are widely applicable to the study of collagenous tissues in health and disease. In particular, observations regarding the pericellular matrix may lead to the development of new tissue–engineered and pharmacological strategies for the treatment of tendon disorders.

No description available.

<p>The extracellular matrix (ECM) plays a significant role in defining the mechanical properties of biological tissues. The proteins, proteoglycans, and glycosaminoglycans that constitute the ECM are arranged into highly organized structures (<i>e.g.</i> fibrils and networks). Cellular behavior is affected by the stiffness of the microenvironment and influenced by the composition and organization of the ECM. Mechanosensing of ECM stiffness by cells occurs at the fibrillar (mesoscale) level between the single molecule (microscale) and the bulk tissue (macroscale) levels. However, the mechanical behavior of ECM proteins at the mesoscale are not well defined. Thus, better understanding of the ECM building blocks responsible for functional tissue assembly is critical in order to recapitulate <i>in vivo</i> conditions. There is a need for the mechanical characterization of the ECM networks formed by proteins synthesized <i>in vivo</i> while in their native configuration. </p> <p>To address this gap, my goals highlighted in this dissertation were to develop appropriate experimental and computational methodologies and investigate the 3D organization and mechanical behavior of ECM networks <i>in situ</i>. The ECM of developing mouse tissues was used as a model system, taking advantage of the low-density networks present at this stage. First, we established a novel decellularization technique that enhanced the visualization of ECM networks in soft embryonic tissues. Based on this technique, we then quantified tissue-dependent strain of immunostained ECM networks <i>in situ</i>. Next, we developed mesoscale and macroscale testing systems to evaluate ECM networks under tension. Our systems were used to investigate tendon mechanics as a function of development, calculating tangent moduli from stress - strain plots. Similarly, we characterized ECM network deformation while uniaxially loading embryonic tissues, since this testing modality is ideal for fibril and network mechanics. Taken together, this information can facilitate the fabrication of physiologically relevant scaffolds for regenerative medicine by establishing mechanical guidelines for microenvironments facilitate functional tissue assembly.</p>

The hands and feet account for half of the complexity of the musculoskeletal system, while the skin of the hand is specialised with many important structures. Much of the subtlety of the mechanism of the hand lies in the soft tissues, and the tactile and proprioceptive sensitivity depends on the large number of mechanoreceptors embedded in specific structures of the soft tissues. This thesis investigates synthetic materials and manufacturing techniques to enable building robots that reproduce the biomechanics and tactile sensitivity of vertebrates – histomimetic robotics. The material and mechanical anatomy of the hand is reviewed, highlighting difficulty of numerical measurement in soft-tissue anatomy, and the predictive nature of descriptive anatomical knowledge. The biomechanical mechanisms of the hand and their support of sensorimotor control are presented. A palate of materials and layup techniques are identified for emulating ligaments, joint surfaces, tendon networks, sheaths, soft matrices, and dermal structures. A method for thermoplastically drawing fine elastic fibres, with liquid metal amalgam cores, for connecting embedded sensors is demonstrated. The performance requirements of skeletal muscles are identified. Two classes of muscle-like bulk MEMS electrostatic actuators are shown theoretically to be capable of meeting these requirements. Means to manufacture them, and their additional application as mechanoreceptors are described. A novel machine perception algorithm is outlined as a solution to the problem of measuring soft tissue anatomy, CAD/CAE/CNC for layup of histomimetic robots, and sensory perception by such robots. The results of the work support the view that histomimetic robotics is a viable approach, and identify a number of areas for further investigation including: polymer modification by graft-polymerisation, automated layup tools, and machine perception.