Development of mechanically robust, biodegradable bioink formulations for 3D bioprinting

Clinical cases including trauma, aggressive tumor ablation and long-term denervation could cause volumetric skeletal muscle loss that necessitate surgical repair since the tissue has limited ability of self-repair and the regenerated tissue is generally co-observed with fibrosis leading to poor functional and mechanical properties. Along with scarcity of the donor tissue available for transplantation in the surgical treatments, they are generally accompanied by significant donor site morbidity. As a result of these shortcomings, engineering functional skeletal muscle tissue via tissue engineering technique holds great promise for the remediation of the aforementioned clinical cases. One of the expanding application areas of this technique is 3D printing, with the potential to produce personalized and anatomically correct structures. In addition, the production of living tissue substitutes is possible with 3D bioprinting that makes use of the bioinks. However, there are some current limitations of the technique, such as the unavailability of an ideal bioink material with suitable rheological, mechanical and elastic properties that match that of skeletal muscle, as well as proper cell-material interactions. Therefore, there is a need for the development of biocompatible and biodegradable, novel biomaterials with suitable mechanical properties that can mimic the structure and function of skeletal muscle tissue for use in 3D bioprinting applications. Polyurethanes (PU) are biomaterials composed of "soft" and "hard" segments chemically linked along a macromolecular backbone. With the appropriate design, selection and chemical combination of hard and soft segments, it is possible to obtain PUs with desired flexibility, mechanical strength and properties. In this thesis, PU-based, light-curable novel bioink materials were developed. Structural and mechanical characterization of the novel materials were performed, along with assessment of 3D printability and stability after cross-linking. Moreover, cytotoxicity assessment and in vitro analysis with C2C12 mouse myoblasts were performed. Among the plethora of PUs synthesized, methacrylated polyurethane (PUMA)-6 was found to be suitable as a light-curable, biocompatible and biodegradable bioink material.