Glycosaminoglycan-inspired biomaterials for the development of bioactive hydrogel networks

Glycosaminoglycans (GAG) are long, linear polysaccharides that display a wide range of relevant biological roles. Particularly, in the extracellular matrix (ECM) GAG specifically interact with other biological molecules, such as growth factors, protecting them from proteolysis or inhibiting factors. Additionally, ECM GAG are partially responsible for the mechanical stability of tissues due to their capacity to retain high amounts of water, enabling hydration of the ECM and rendering it resistant to compressive forces. In this review, the use of GAG for developing hydrogel networks with improved biological activity and/or mechanical properties is discussed. Greater focus is given to strategies involving the production of hydrogels that are composed of GAG alone or in combination with other materials. Additionally, approaches used to introduce GAG-inspired features in biomaterials of different sources will also be presented.The authors would like to acknowledge FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior in the framework of Project ANGIONICHE (POCI-01-0145-FEDER-028744 and PTDC/BTMMAT/28744/2017). The authors thank FCT for the doctoral grant SFRH/BD/129855/2017 to Mariana I. Neves and the research position IF/00296/2015 to Cristina C. Barrias. Ricardo M. P. da Silva thanks FEDER and FCT for a researcher contract in the framework of Project Soft Strong (POCI-01-0145-FEDER-032431 and PTDC/CTM-COM/32431/2017). Marco Araújo gratefully acknowledges Agência para o Desenvolvimento e Coesão and Ministerio de Hacienda, Dirección General de Fondos Europeos for Interreg V-A Spain–Portugal (POCTEP) 2014–2020 and FEDER (0245_IBEROS_1_E) for the postdoctoral grant