Plasma surface functionalization: A comprehensive review of advances in the quest for bioinstructive materials and interfaces

Surface biofunctionalization aims to create cell-instructive surfaces that control the behavior of cells and modulate cellular interactions by incorporating cell signaling moieties at the materials–biosystem interface. Despite advances in developing bioinert and biocompatible materials, blood clotting, inflammation, and cell death continue to be observed upon the contact of foreign materials with living tissues leading to the materials' rejection. Specific examples include the application of foreign materials in implantable devices (e.g., bone implants, antimicrobial surfaces, and cardiovascular stents), biosensors, drug delivery, and 3D-bioprinting. Biofunctionalization of materials to date has been predominantly realized using wet chemical approaches. However, the complexity of wet chemistry, toxicity of reactants, waste disposal issues, reaction time, poor reproducibility, and scalability drive a need for a paradigm shift from wet chemical approaches to dry methods of surface biofunctionalization. Plasma-based technologies that enable covalent surface immobilization of biomolecules have emerged as dry, reagent-free, and single-step alternatives for surface biofunctionalization. This review commences by highlighting the need for bioinstructive surfaces and coatings for various biomedical applications such as bone implants, antimicrobial surfaces, biosensors, and 3D-bioprinted structures, followed by a brief review of wet chemical approaches for developing biofunctionalized surfaces and biomimetic devices. We then provide a comprehensive review of the development of plasma-based technologies for biofunctionalization, highlighting the plasma–surface interactions and underpinning mechanisms of biomolecule immobilization.