Bio-inspired Materials:Preparation And Their Interaction With Proteins And Cells

Bio-inspired materials are a type of new materials which are inspired by structures and functions of natural bio-materials and have similar bio-functions. Bio-inspiring strategies are widely used in the field of biomaterials. Functions of bio-inspired materials are achieved by mimicking interactions between proteins and signaling pathways through cells. There are two types of interactions between biomaterials:active binding and inert repulsion. Active binding facilitates the realization of physiological activities, while inert repulsion is the basis for specificity and accuracy of biological activation. Therefore, bio-inspiring strategies should be developed with the idea of combining active binding and inert repulsion:to activate targeting biological processes specifically on the basis of inert repulsion, which guarantees functional effectiveness. The bio-inspiring strategy should be focused on mimicking functional molecular structures of biomaterials to realize similar biological interactions.Cells are basic structures and functional units of life. Their constructions and functions rely on particular structures of cell membranes. Phospholipid bilayers provide inert screens for cells, while membrane proteins and sugars mediate exchanges of signaling, substances and energy in and out of the cells. Among them, glycosaminoglycans (GAGs) are proved to be able to regulate stem cell differentiation. Based on bio-inspiring strategies, GAGs and inert phospholipid molecular structures are mimicked through molecular design, and functions of regulating stem cell differentiation and resisting protein adsorption of the bio-inspired materials are studied in this paper.1. Synthesis of membrane sugar-inspired GAG-mimetics and their influences on stem cell neural differentiation. GAGs can exist on cell membranes. They interact with a variety of proteins in extra cellular matrics through electrostatic interacitons and mediate cell signaling pathways, thus regulating stem cell behavior. However, batch-to-batch heterogeneity and immunogenicity limit their application in biological engineering. Through molecular design, GAG-mimetics with defined structures are fabricated by mimicking functional structures, and the corresponding bio-functions are achieved. Since sulphated groups and glycol units are main functional structures of GAGs, this paper combines those units together in small molecules and copolymers respectively, to fabricate GAG-mimetics.First, ?-cyclodextrin (?-CD) is sulphated to fabricated sulphated (3-CD as GAG-mimetics. The thiol-bromo click reaction and the copper (1)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction are utilized respectively, to obtain sulphated ?-CDs with different structures:?-CD-(S-SO3Na)7 and ?-CD-(N3-SO3Na)7. It showed that those molecules can both support L929 cell and embryonic stem cell proliferation, with the similar effect to heparin, demonstrating their good biocompatibilities. In the process of stem cell neural differentiation, both ?-CD-(S-SO3Na)7 and ?-CD-(N3-SO3Na)7 showed better effectiveness than heparin in promoting stem cell neural specification. With 14 day-treatment, ?-CD-(S-SO3Na)7 and ?-CD-(N3-SO3Na)7 promoted stem cell neural differentiation 1.2-and 1.9-fold of heparin. Meanwhile, ?-CD has no significant difference comparing to the control group. Stem cells in those groups only showed the potential of neural differentiation 0.6-fold of those with the treatment of heparin. Therefore, through sulfation of ?-CD, the ability of GAGs to regulate stem cell differentiation is mimicked.Furthermore, in order to mimic the polymeric structures of GAGs and to regulate relative ratios of functional components, a new strategy of synthesizing GAG-mimetics is developed. "Sulfate unit" and "glycol unit" in GAGs are "splitted" and considered as independent building blocks. First, two molecules, sodium 4-vinylbenzenesulfonate (SS) and 2-methacrylamido glucopyranose (MAG) containing "sulfonated unit" and "glycol unit" respectively are selected as monomers, and copolymerize through RAFT. The ratios of SS and MAG are controllable by changing initial ratios. L929 cell proliferation showed the good biocompatibilities of synthesized GAG-mimicking polymers. The addition of those polymers also promoted stem cell proliferation. In addition, it is found that GAG-mimicking polymers have the ability to promote stem cell neural specification with different ranges. pS1G1 (SS/MAG is around 1/1) promotes stem cell neural differentiation 3.1-fold of heparin. Therefore, bio-functions that are even better than natural GAGs can be obtained by regulating constitutions of functional components.2. Fabrication of surfaces modified with phospholipid bilayer-inspired zwitterionic polymers and their anti-protein adsorption properties. The zwitterionic structures of the out layers of phospholipid bilayers are key factors for cell membranes as inert screens of cells. Therefore, surfaces modified with zwitterionic materials have good "nonfouling" properties. It is important to develop a versatile strategy to modify most of surfaces using zwitterionic materials. In this paper, zwitterionic polymers with adhesive molecules 3,4-dihydroxyphenyl-L-alanine (DOPA) in the end are grafted onto material surfaces, and their abilities of resisting protein adsorption are studied. Atom transfer radical polymerization (ATRP) initiators functionalized with DOPA are used to initiate polymerization of sulfobetaine (SB) and carboxybetaine (CB) respectively. In this way, poly (sulfobetaine) (pSB) and poly (carboxybetaine) (pCB) with different molecular weights are fabricated respectively. Synthesized pSBs and pCBs are grafted onto polydimethylsiloxane (PDMS) surfaces. Protein adsorption results showed that the increase of molecular weight of polymers in a range is beneficial to improve anti-adsorption properties of modified surfaces. Increasing the number of DOPA in the end of the polymer facilitates getting denser polymer layers, and therefore improving anti-adsorption properties of modified surfaces. Besides, the addition of small molecules dopamine also assist to increase the density of polymer brushes and thus reduce protein adsorption.Inspired by cell membranes, GAG-mimetics with bio-activities and zwitterionic polymers-modified surfaces with bio-inertness are fabricated. Future works should be focused on combining those materials on material interfaces to resist nonspecific adsorption and promote targeting bioactivities at the same time, and to develop advanced bio-inspired materials.