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Novel dynamic self-assembling system: from hierarchical and biomimetic morphogenesis to functional materials

Final Report Summary - BIOMORPH (Novel dynamic self-assembling system: from hierarchical and biomimetic morphogenesis to functional materials)

Nature has evolved in a hierarchical manner through an optimization of molecules such as nucleic acids, amino acids, and saccharides into a diverse repertoire of macromolecules such as DNA, proteins, and other biopolymers. Of these, proteins are arguable the most sophisticated and functional and Nature uses them as part of multicomponent self-assembling systems. In fact, biological materials acquire most of their structural complexity and corresponding functionality as a result of their ability to assemble proteins with other molecules at multiple scales. Biomorph aims to use proteins as part of multicomponent self-assembling systems to create materials with innovative properties. Towards this goal, Biomorph aims to develop a reproducible and tuneable self-assembling strategy to create a dynamic material that can be grown to acquire complex geometries and can be engineered to fabricate bioactive and biomimetic scaffolds. The specific objectives of the project were: a) design peptide amphiphile (PA) and elastin-like proteins (ELPs) to co-assemble into well-defined nanostructures, b) develop a co-assembling system that is tunable and can generated hierarchical structures and new properties that are advantageous for tissue engineering, c) develop complex tubular scaffolds and d) characterize their mechanical, chemical, and bioactive properties.

We have successfully designed a material that integrates ELPs with PAs and exhibits the capacity to grow into desired shapes and under specific conditions undergo morphogenesis and self-healing. In the process, we have discovered a new molecular mechanism based on the co-assembly of PAs and ELPs, the generation of a diffusion-reaction assembly process, and the capacity of the ELP to modify its conformation thanks to its inherent disordered structure. This mechanism has opened up a new way to grow materials based on the modulation of protein order and disorder and the capacity of PAs to serve as chaperones in this process. Furthermore, the process was then used to create complex scaffolds for tissue engineering, which we have demonstrated to be compatible, enhance and control cell adhesion, promote angiogenesis, and be able to be grown in the presence of cells. The scaffolds support endothelial cell adhesion and proliferation up to the point of confluency, generating an endothelialised tubular scaffold. These materials will have important implications in the development of new tissue engineering strategies as well as in vitro models such as organs-on-chip.