| Summary: | <p>Surgical repair of rotator cuff tears is often inadequate and can lead to re-tearing of up to 40% of surgical cases, and ensuing pain and disability. The reason for surgical failure has often been attributed to the poor intrinsic healing qualities of the tendon itself in combination with a lack of congruence at the bone-tendon interface (enthesis). Despite the advances made with surgical materials and techniques, little progress has been achieved in improving the biological response of torn tendons. Tissue engineering and the development of biomaterials offer promising strategies to support the healing process.</p>
<p>The aim of this thesis was to develop a biphasic biomaterial or scaffold, consisting of a soft electrospun part and a hard 3D printed part, in the context of rotator cuff repairs. Electrospun fibres are promising materials to support tendon healing because they can be designed to resemble the hierarchical architecture of native tendon extracellular matrix. In addition, 3D printed structures have well-known applications in bone-tissue engineering because they can be designed with a similar porosity and pore size to bone matrix. The main objectives will be to create a biphasic scaffold consisting of an electrospun soft cuff and a 3D printed hard block, evaluate the biological activity of the electrospun filaments and set the dimensions of the 3D printed part using anatomical measurements and anonymised medical imaging.</p>
<p>To achieve the biphasic scaffold, a layer-by-layer method to insert pre-assembled bundles of electrospun filaments in the 3D printing process was first used. The resulting scaffold was scaled up to increase its mechanical strength and reach a threshold value of 250N that is of clinical relevance. Second, the cuff component was evaluated against a commercial suture and although there was no difference in cell attachment between them, cells were elongated and spindle-shaped on the former and showed a profile of differentially expressed genes related to development and proliferation, angiogenesis, and extracellular matrix organization. Thirdly, the design of the 3D printed component was improved to fit the geometry of the greater tuberosity of the humerus, using medical imaging, resulting in three prototypes with different fixation methods. The prototypes were tested in a porcine model ex vivo and failure mechanisms were identified using physiologically relevant cyclic loadings.</p>
<p>Future work should focus on automatizing the manufacturing process and on further improving the strength of the biphasic scaffold by changing the cuff design and inserting more filaments. Furthermore, the bioactivity and biocompatibility of the soft and hard components should be evaluated more thoroughly with use of clinically relevant cell types in co-culturing systems or by use of bioreactors. Finally, the designs of the proposed biphasic scaffold need to be evaluated in a model system resembling human anatomy, physiology and biomechanics over a prolonged period of time.</p>
<p>In conclusion, this thesis proposes a novel method for the manufacture of a soft-hard scaffold, using state-of-the-art tissue engineering biomaterial technologies, electrospinning and 3D printing. While it shows potential for rotator cuff tendon repair, this work also contributes to the wider research community investigating multiphasic scaffolds for various clinical applications.</p>
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