Engineered dual affinity protein fragments to bind collagen and capture growth factors

Sarrigiannidis, S. O., Dobre, O. , Navarro, A. R., Dalby, M. J. , Gonzalez-Garcia, C. and Salmeron-Sanchez, M. (2023) Engineered dual affinity protein fragments to bind collagen and capture growth factors. Materials Today Bio, 20, 100641. (doi: 10.1016/j.mtbio.2023.100641) (PMID:37179535) (PMCID:PMC10173277)

Abstract

Collagen type I lacks affinity for growth factors (GFs) and yet it is clinically used to deliver bone morphogenic protein 2 (BMP-2), a potent osteogenic growth factor. To mitigate this lack of affinity, supra-physiological concentrations of BMP-2 are loaded in collagen sponges leading to uncontrolled BMP-2 leakage out of the material. This has led to important adverse side effects such as carcinogenesis. Here, we design recombinant dual affinity protein fragments, produced in E. Coli, which contain two regions, one that spontaneously binds to collagen and a second one that binds BMP-2. By adding the fragment to collagen sponges, BMP-2 is sequestered enabling solid phase presentation of BMP-2. We demonstrate osteogenesis in vivo with ultra-low doses of BMP-2. Our protein technology enhances the biological activity of collagen without using complex chemistries or changing the manufacturing of the base material and so opens a pathway to clinical translation.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Salmeron-Sanchez, Professor Manuel and Dobre, Dr Oana and Sarrigiannidis, Stylianos and Gonzalez Garcia, Dr Cristina and Dalby, Professor Matthew
• Authors: Sarrigiannidis, S. O., Dobre, O., Navarro, A. R., Dalby, M. J., Gonzalez-Garcia, C., and Salmeron-Sanchez, M.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Research Centre: Mazumdar-Shaw Advanced Research Centre (ARC) > Technologies Touching Life
• Journal Name: Materials Today Bio
• Publisher: Elsevier
• ISSN: 2590-0064
• ISSN (Online): 2590-0064
• Published Online: 22 April 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Materials Today Bio 20: 100641
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
173192		Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicine	Manuel Salmeron-Sanchez	Engineering and Physical Sciences Research Council (EPSRC)	EP/P001114/1	ENG - Biomedical Engineering
301095		UKRMP2 Acellular/Smart Materials 3D Architecture Hub	Manuel Salmeron-Sanchez	Medical Research Council (MRC)	MR/R015651/1	ENG - Biomedical Engineering