Biomaterials for sequestration of growth factors and modulation of cell behavior

Growth factors (GFs) are proteins secreted by cells that regulate a variety of biological processes. Although they have long been proposed as potent therapeutic agents, their administration in a soluble form has proven costly and ineffective due to their short halfâ lives in biological environments. Biomaterialâ based approaches are increasingly sought as alternatives to improve the efficacy or, ideally, replace the need for exogenous administration of GFs in regenerative medicine strategies. The means by which these systems evolve from biomaterials for conventional controlled release of GFs to the recent extracellular matrix (ECM)â inspired approaches for sequestering these labile molecules and regulating their spatiotemporal activity and presentation are reviewed. Focus is placed on biomaterials functionalized either with ECM components, which show promiscuous GF binding, or with targeted GF ligands (antibodies, aptamers, or peptides). The potential of synthetic platforms with abiotic affinity as costâ effective alternatives to the current biological ligands is also discussed. Overall, the various GF sequestering systems developed so far have remarkably improved the activity of GFs at reduced doses and, in some cases, completely avoided the need for their exogenous administration to guide cell fates. These bioinspired concepts thus enable the rational exploration of the full therapeutic potential of GFs in regenerative medicine. The authors acknowledge the financial support from project NORTE-01- 0145-FEDER-000021 supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant Agreement No 739572 — The Discoveries CTR EU, Twinning Grant agreement No 810850 — Achilles, European Research Council Grant Agreement No 772817; FCT/MCTES (Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia, e Ensino Superior), and the Fundo Social Europeu através do Programa Operacional do Capital Humano (FSE/POCH) in the framework of Ph.D. Grant PD/169/2013–PD/BD/143039/2018 for S.P.B.T., and project Grant PTDC/NAN-MAT/30595/2017.