The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development

Collagen is the oldest and most abundant extracellular matrix protein that has found many applications in food, cosmetic, pharmaceutical, and biomedical industries. First, an overview of the family of collagens and their respective structures, conformation, and biosynthesis is provided. The advances and shortfalls of various collagen preparations (e.g., mammalian/marine extracted collagen, cell-produced collagens, recombinant collagens, and collagen-like peptides) and crosslinking technologies (e.g., chemical, physical, and biological) are then critically discussed. Subsequently, an array of structural, thermal, mechanical, biochemical, and biological assays is examined, which are developed to analyze and characterize collagenous structures. Lastly, a comprehensive review is provided on how advances in engineering, chemistry, and biology have enabled the development of bioactive, 3D structures (e.g., tissue grafts, biomaterials, cell-assembled tissue equivalents) that closely imitate native supramolecular assemblies and have the capacity to deliver in a localized and sustained manner viable cell populations and/or bioactive/therapeutic molecules. Clearly, collagens have a long history in both evolution and biotechnology and continue to offer both challenges and exciting opportunities in regenerative medicine as nature's biomaterial of choice.This work forms part of the Teagasc Walsh Fellowship (grant award number: 2014045) and the ReValueProtein Research Project (grant award number: 11/F/043) supported by the Department of Agriculture, Food and the Marine (DAFM) under the National Development Plan 2007–2013 funded by the Irish Government. This work has also been supported from the: Health Research Board, Health Research Awards Programme (grant agreement number: HRA_POR/2011/84); Science Foundation Ireland, Career Development Award Programme (grant agreement number: 15/CDA/3629); Science Foundation Ireland and the European Regional Development Fund (grant agreement number: 13/RC/2073); College of Engineering and Informatics, National University of Ireland Galway; EU FP7/2007-2013, NMP award, Green Nano Mesh Project (grant agreement number: 263289); EU FP7/2007-2013, Health award, Neurograft Project (grant agreement number: 304936); EU H2020, ITN award, Tendon Therapy Train Project (grant agreement number: 676338); National University of Singapore Tissue Engineering Programme (NUSTEP). The authors would like to thank M Doczyk, E Collin, W Daly, M Abu-Rub, D Thomas, S Browne, C Tapeinos, A Satyam and D Cigognini for their help in producing the figures. A.S., L.M.D., Z.W., N.S., A.K., R.N.R., A.M.M., A.P., M.R., and D.I.Z. have no competing interests. Y.B. is an employee of Sofradim Production – A Medtronic Company. D.I.Z would like to dedicate the manuscript to A.G.Z. who left and A.D.Z. who camepeer-reviewe

The collagen suprafamily : from biosynthesis to advanced biomaterial development

Biomimetic microenvironments are key components to successful cell culture and tissue engineering in vitro. One of the most accurate biomimetic microenvironments is that made by the cells themselves. Cell-made microenvironments are most similar to the in vivo state as they are cell-specific and produced by the actual cells which reside in that specific microenvironment. However, cell-made microenvironments have been challenging to re-create in vitro due to the lack of extracellular matrix composition, volume and complexity which are required. By applying macromolecular crowding to current cell culture protocols, cell-made microenvironments, or cell-derived matrices, can be generated at significant rates in vitro. In this review, we will examine the causes and effects of macromolecular crowding and how it has been applied in several in vitro systems including tissue engineering