Epitope-imprinted polymers: design principles of synthetic binding partners for natural biomacromolecules

Molecular imprinting (MI) has been explored as an increasingly viable tool for molecular recognition in various fields. However, imprinting of biologically relevant molecules like proteins is severely hampered by several problems. Inspired by natural antibodies, the use of epitopes as imprinting templates has been explored to circumvent those limitations, offering lower costs and greater versatility. Here, we review the latest innovations in this technology, as well as different applications where MI polymers (MIPs) have been used to target biomolecules of interest. We discuss the several steps in MI, from the choice of epitope and functional monomers to the different production methods and possible applications. We also critically explore how MIP performance can be assessed by various parameters. Last, we present perspectives on future breakthroughs and advances, offering insights into how MI techniques can be expanded to new fields such as tissue engineering.This work was supported by Project NORTE-01-0145-FEDER-000021 supported by the Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); by the European Union Framework Program for Research and Innovation HORIZON 2020, under the Twinning grant agreement no. 810850–Achilles, European Research Council grant agreement no. 772817; and by FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia, e Ensino Superior) through PhD grant PD/BD/143039/2018 for S.P.B.T., financed through the Doctoral Program in Advanced Therapies for Health (PATH) (FSE/POCH/ PD/169/2013), project PTDC/NAN-MAT/30595/2017, and individual contract 2020.03410. CEECIND for R.M.A.D. N.A.P. acknowledges support from the Cockrell Family Chair Foundation; the Institute for Biomaterials, Drug Delivery, and Regenerative Medicine; and the UT-Portugal Collaborative Research Program