Plasma Technologies for the Creation of Tailorable Biosignalling Interfaces for Cell Culture Materials, Porous 3D Scaffolds and Micro/Nanoparticles

Modern biomedical research and clinical practice rely on a wide range of materials formed into complex structures to provide suitable environments for cells and tissues. These materials range from metals and glasses to plastics and hydrogels. Constraints on mechanical and optical properties required for particular in-vivo and in-vitro applications are usually not compatible with providing the optimum biological microenvironments for the interfacing cell types.<br/><br/>Here we describe rapid, wet-chemistry-free, plasma-based approaches that utilize environmentally-friendly ionized gases to activate a range of materials and structures for spontaneous, reagent-free, covalent functionalization with bioactive molecules. Molecules that can be immobilized whilst retaining their functions include but are not limited to oligonucleotides, enzymes, peptides, aptamers, cytokines, antibodies, cell-adhesion extra-cellular matrix molecules and histological dyes. Their immobilization occurs via surface-embedded radicals that are created by energetic ions from the ionized gas bombarding the materials' surfaces prior to contact with the biomolecules [1]. Typical time scales of cell cultures necessitate covalent tethering because physical bonding would be susceptible to exchange with biomolecules from the culture media and robust spatial patterning of the molecules is required to replicate physiologically relevant structures.<br/><br/>This presentation will examine the fundamental science and process adaptions that enable such surface modifications to be applied to the internal surfaces of multi-well plates, complex, porous materials and micro/nanostructures whilst retaining favorable optical properties. Strategies to pattern immobilized molecules on the surfaces will be examined. Applications enabling biological studies of the response of individual cells to proteins on a sub-cellular scale [3], and the preparation of multi-functionalizable nanoparticles [4] will be discussed. The surface embedded radicals are shown to enable polymerization of hydrogels from thus activated surfaces [5] and control of the density and orientation of surface-immobilized bioactive peptides through pH variations and/or the application of external electric fields during the immobilization [6].<br/><br/>[1] <i>PNAS </i> <b>108</b>:14405-14410 (2011);<br/>[2] <i>ACS Appl. Mater. and Interfaces</i> (2018);<br/>[3] <i>ACS Appl. Nano Materials </i>(2018);<br/>[4] <i>Adv. Funct. Materials</i> (2020);<br/>[5] <i>Nat. Comm. </i>9:357 (2018)