Strategies to design and optimize natural polymers as biomaterial inks for musculoskeletal tissue engineering applications

Three-dimensional bioprinting is an advanced fabrication technology which exploits additive manufacturing techniques to develop scaffolds with precise spatial control for biomedical applications. Among the existing technologies, extrusion-based bioprinting gained an increased interest in fabricating complex tissue constructs due to its high throughput and versatility in processing materials with a broad range of viscosities and viscoelastic properties. However, one of the major challenges in designing printable biomaterial inks is achieving the required rheological properties, as the starting point is usually a polymeric aqueous solution or a pre-crosslinked hydrogel. Moreover, the lack of specific standardized testing methods for bioprinted products set a gap between research and their clinical translations. This thesis focuses on the design and optimization of inks derived from natural polymers, aiming to address critical challenges in printability and biocompatibility for bone tissue engineering applications. Most of the research was carried out on silk fibroin, a protein commonly used for tissue engineering scaffold fabrication owing to its promising physical and biological properties, although it lacks the rheological properties required for extrusion-based bioprinting. Different approaches have been explored to improve its printability: blending with hyaluronic acid, use of ultrashort self-assembling peptides and incorporation of inorganic fillers. Moreover, the biological outcomes of the scaffolds were tuned with the addition of different bioactive cues (i.e. tropoelastin or bioceramics) providing a versatile platform for the development of biomaterial inks for bone regeneration.