Surface biofunctionalization to improve the efficacy of biomaterial substrates to be used in regenerative medicine

Surface biofunctionalization has emerged in the past decade as a rising tool in Tissue Engineering and Regenerative Medicine (TERM) approaches. The development of biomaterial substrates with regenerative properties is challenging, mainly due to the requirement of obtaining a surface that promotes cell attachment, proliferation and differentiation. Biomolecules, namely extracellular matrix proteins and growth factors, play a key role in the wound healing cascade, mediating a wide range of cellular activities. Therefore, the immobilization of such biomolecules at the surface of biomaterials has a remarkable interest for TERM strategies. Numerous variants can be used to biofunctionalize the surface of biomaterials, being classified as non-covalent and covalent immobilization strategies. Importantly, the maintenance of stable/available bioactive factors needs also to be considered. In this review, a wide range of bioactive molecules and different biofunctionalization strategies will be discussed, as well as the most relevant results achieved in the novel and most promising strategies.