Extracellular matrices (ECMs) in tissues and organs are critical for cell self-renewal, differentiation, reprogramming, function, and organization. Development of materials that can mimic the native ECMs will contribute not only to fundamental biological studies but also to tissue engineering and regenerative medicine. Artificial ECMs have evolved from those initially composed of synthetic polymers to those entirely built upon engineered protein polymers. Synthetic polymers are often constrained by limited biological functionality, alongside significant concerns over their cytotoxicity, biocompatibility, biodegradability for biomedical use. Benefiting from synthetic biology and protein engineering, the properties and biological activities of those emerging engineered protein materials c...[ Read more ]

Extracellular matrices (ECMs) in tissues and organs are critical for cell self-renewal, differentiation, reprogramming, function, and organization. Development of materials that can mimic the native ECMs will contribute not only to fundamental biological studies but also to tissue engineering and regenerative medicine. Artificial ECMs have evolved from those initially composed of synthetic polymers to those entirely built upon engineered protein polymers. Synthetic polymers are often constrained by limited biological functionality, alongside significant concerns over their cytotoxicity, biocompatibility, biodegradability for biomedical use. Benefiting from synthetic biology and protein engineering, the properties and biological activities of those emerging engineered protein materials can be delicately controlled by genetic programming. The ecological diversity of naturally occurring protein molecules, together with the might of protein engineering, provides extra assurance to meet the increasing demand for dynamic “smart” biomaterials.

While three-dimensional (3D) material systems are often considered to be more desirable ─ and therefore better studied ─ for recapitulating the real native extracellular microenvironment in vivo, lower dimensional materials such as 1D fibres, characterized by their simplicity and patternability, have yet to be explored for their potential in materials biology and regenerative medicine. In Chapter 1, we have an overview over 1D- and 3D-biomaterials (i.e., silks and hydrogels) and discuss the impact of synthetic biology and biomolecular engineering on their design and development. In Chapter 2, we describe the development of 1D protein materials, Spy spider silks, that, thanks to SpyTag/SpyCatcher chemistry, not only allow for various modifications with bioactive proteins and biomineralization but also are suitable for 1D cell attachment and culturing, the latter of which might open up new opportunities for tissue regeneration. In Chapter 3, we illustrate the creation of injectable, photoresponsive protein hydrogels ─ 3D smart materials ─ via metal-mediated protein assembly and their use in therapeutic delivery and axon regeneration. In Chapter 4, we summarize the chief findings in this thesis study and further discuss the possible applications of the protein materials in areas in optical biosensing, on-chip biotechnologies, and so on.

Together, the thesis illustrates the creation of entirely protein-based 1D- and 3D-materials that hold great promise for biomedical applications.