From small to large-scale: a review of recombinant spider silk and collagen bioproduction

Abstract Advancements in material science have led to the development of new composites and biomaterials. Spider silk and human collagen are examples of animal-derived polymers for which sourcing has been challenging. Interest in strong, sustainable products derived from these biopolymers and increasing demand in bio-based solutions are driving forces for investments in non-animal-based production processes namely for use in biomedical applications. An outline of the current landscape of microbial-based bioprocesses is a useful tool to guide further development of novel biomaterials based on these proteins. While bioproduction can deliver a sustainable source for human collagen and for spider silk, it has been challenging to obtain the desired products via microbial-based bio-industrial processes. Optimization through improvements in upstream processes and better adapted large-scale downstream process steps, including replacing chromatography steps with freeze drying and autoclaving for endotoxin removal (silk) and filtration (collagen) has enabled large-scale production and recent capacity expansion of manufacturing, aiming to deliver hundreds of tonnes of product per year. This article reviews the considerable advances that were made in microbial processes for production of human collagen and spider-silk based biomaterials in the past 30 years in translating the laboratory results into scalable processes. Main challenges for successful large-scale implementation—such as recombinant silk durability and the continuous need to improve process economics—and main opportunities such as demand growth of recombinant spider silk and human collagen are outlined.