Heher, P. (2018). Strategies to control cellular behavior in fibrin-based three-dimensional musculoskeletal tissue engineering approaches [Dissertation, Technische Universität Wien]. reposiTUm. https://doi.org/10.34726/hss.2018.60243
Musculoskeletal disorders are the most common cause of severe long term pain and physical disability in 1st world countries, thus creating an immense socio-economic burden. There is no cure for acute or chronic muscle pathologies and current treatments are limited to highly invasive grafting procedures. The field of skeletal muscle tissue engineering has thus developed alternate strategies to address the shortcomings of current therapies. Skeletal muscle tissue engineering approaches employ the culture of muscle precursor cells in suitable biomaterial substrates until a functional, biomimetic muscle construct is generated which can subsequently be used as a transplant or as (disease) modelling platform. In doing so, the field has recently focused on more sophisticated, dynamic cell culture systems that account more precisely for the complex nature and physiology of skeletal muscle, with the aim of further increasing the functionality of in vitro engineered muscle tissue. This thesis presents such a novel dynamic culture system which allows for the rapid generation of functional skeletal muscle tissue through bioreactor-based, automated application of defined mechanical stimulation regimes. Furthermore, it illustrates a reporter system for myogenic differentiation which can be implemented into this dynamic culture model for noninvasive, longitudinal sampling in order to save costs and time. In addition, an interpenetrating polymer network strategy for structural reinforcement of fibrin hydrogels, which are versatile but comparably soft cell and differentiation matrices for tissue engineering, is presented, along with comprehensive reviews on the manifold features of fibrin sealants/hydrogels for therapeutic delivery of cells or drugs in regenerative medicine.
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