More than just bare scaffolds: towards multi-component and decorated fibrous biomaterials

Abstract

We are entering a new phase in biomaterials research in which rational design is being used to produce functionalised materials tailored to specific applications. As is evident from this Themed Issue, there are now a number of distinct types of designed, self-assembling, fibrous biomaterials. Many of these are ripe for development and application for example as scaffolds for 3D cell culture and tissue engineering, and in templating inorganic materials. Whilst a number of groups are making headway towards such applications, there is a general challenge to translate a wealth of excellent basic research into materials with a genuine future in real-life applications. Amongst other contemporary aspects of this evolving research area, a key issue is that of decorating or functionalising what are mostly bare scaffolds. There are a number of hurdles to overcome to achieve effective and controlled labelling of the scaffolds, for instance: maintaining biocompatibility, i.e., by minimising covalent chemistry, or using milder bioconjugation methods; attaining specified levels of decoration, and, in particular, high and stoichiometric labelling; introducing orthogonality, such that two or more functions can be appended to the same scaffold; and, in relevant cases, maintaining the possibility for recombinant peptide/protein production. In this critical review, we present an overview of the different approaches to tackling these challenges largely for self-assembled, peptide-based fibrous systems. We review the field as it stands by placing work within general routes to fibre functionalisation; give worked examples on our own specific system, the SAFs; and explore the potential for future developments in the area. Our feeling is that by tackling the challenges of designing multi-component and functional biomaterials, as a community we stand to learn a great deal about self-assembling biomolecular systems more broadly, as well as, hopefully, delivering new materials that will be truly useful in biotechnology and biomedical applications (107 references).

Cryo-transmission electron microscopy structure of a gigadalton peptide fiber of de novo design

“…From a more-applied perspective, interest in peptide-and protein-based fibrous biomaterials has increased recently because these materials have potential applications in biotechnology and synthetic biology-for example, as scaffolds for 3D cell culture, tissue engineering, and templating the assembly of functional inorganic materials (10)(11)(12)(13). Although natural proteins can and are being used in these areas, much simpler or stripped-down systems are preferable because they reduce complexity, and potentially allow better understanding and control over the folding and assembly processes leading to fiber formation.…”

“…Although natural proteins can and are being used in these areas, much simpler or stripped-down systems are preferable because they reduce complexity, and potentially allow better understanding and control over the folding and assembly processes leading to fiber formation. Indeed, the past decade has witnessed a plethora of successful peptide-based designs of fibrous biomaterials encompassing dipeptides, β-hairpins, protein fragments, peptide-organic hybrids, and peptide amphiphiles, which are based mainly on β-sheet structures (12,14). However, no design process is complete until the structures of the components and their assemblies have been determined to high resolution to afford molecular and, ideally, atomistic descriptions.…”

Hyperthin nanochains composed of self-polymerizing protein shackles

“…Furthermore some proteins, such as actin 1 , collagen 2 and amyloid 3 , form fibrils held together by intermolecular interactions. As these sophisticated structures can be constructed without special equipment, fibrils made of either natural or artificial proteins have been studied for use in various functional materials [4][5][6] . For example, fibrils have been used as scaffolds for metals 7,8 and functional proteins 9,10 and as networks for tissue engineering applications 11 .…”

Nanostructured functional films from engineered repeat proteins

“…In spite of our increased understanding of interactions that govern assemblies in nature, in the laboratory, there is still a challenge to make controlled assemblies that span scales over several orders of magnitude. Self-assembling materials based on peptides, proteins and nucleic acids have recently been explored [2,[4][5][6][7][8][9][10][11][12][13][14]. In this work, we focus on protein materials because proteins provide a large repertoire of interactions and chemical reactivities that can in turn provide function to the materials [15].…”