Protein scaffolds in human clinics

ElsevierVolume 61, December 2022, 108032Biotechnology AdvancesHighlights•

Drug delivery and regenerative medicine require mechanically stable scaffolds.

Proteins are excellent building blocks for designing nano- and microscale constructs.

Protein scaffolds can be further functionalized by mutagenesis or domain engineering.

Humanization of protein scaffolds is required for clinical applications.

Abstract

Fundamental clinical areas such as drug delivery and regenerative medicine require biocompatible materials as mechanically stable scaffolds or as nanoscale drug carriers. Among the wide set of emerging biomaterials, polypeptides offer enticing properties over alternative polymers, including full biocompatibility, biodegradability, precise interactivity, structural stability and conformational and functional versatility, all of them tunable by conventional protein engineering. However, proteins from non-human sources elicit immunotoxicities that might bottleneck further development and narrow their clinical applicability. In this context, selecting human proteins or developing humanized protein versions as building blocks is a strict demand to design non-immunogenic protein materials. We review here the expanding catalogue of human or humanized proteins tailored to execute different levels of scaffolding functions and how they can be engineered as self-assembling materials in form of oligomers, polymers or complex networks. In particular, we emphasize those that are under clinical development, revising their fields of applicability and how they have been adapted to offer, apart from mere mechanical support, highly refined functions and precise molecular interactions.

Keywords

Protein materials

nanomedicine

drug delivery

regenerative medicine, self-assembling

human protein

humanization

© 2022 The Authors. Published by Elsevier Inc.

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