https://orbilu.uni.lu/bitstream/10993/21149/1/Advantages%20and%20challenges%20of%20microfluidic%20cell%20culture%20in%20polydimethylsiloxane%20devices.pdf

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Fouling initiated by nonspecific protein adsorption is a great challenge in biomedical applications, including biosensors, bioanalytical devices, and implants Poly(dimethylsiloxane) (PDMS), a popular material with many attractive properties for device fabrication in the biomedical field, suffers serious fouling problems from protein adsorption due to its hydrophobic nature, which limits the practical use of PDMS-based devices Effort has been made to develop biocompatible materials for anti-fouling coatings of PDMS In this review, typical nonfouling materials for PDMS coatings are introduced and the associated basic anti-fouling mechanisms, including the steric repulsion mechanism and the hydration layer mechanism, are described Understanding the relationships between the characteristics of coating materials and the accompanying anti-fouling mechanisms is critical for preparing PDMS coatings with desirable anti-fouling properties

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Anti-fouling Coatings of Poly(dimethylsiloxane) Devices for Biological and Biomedical Applications

Graphene oxides with different surface charges were fabricated from carboxylated graphene oxide by chemical modification with amino- (-NH2), poly-m-aminobenzene sulfonic acid- (-NH2/-SO3H), or methoxyl- (-OCH3) terminated functional groups. The chemically functionalized graphene oxides and the carboxylated graphene oxide were characterized by infrared spectroscopy, X-ray photoelectron spectroscopy, UV-Vis spectrometry, ζ potential measurements, field emission scanning electron microscopy, and contact angle analyses. Subsequently, the resulting graphene oxides were used as substrates for culturing primary rat hippocampal neurons to investigate neurite outgrowth and branching. The morphological features of neurons that directly reflect their potential capability in synaptic transmission were characterized. The results demonstrate that the chemical properties of graphene oxide can be systematically modified by attaching different functional groups that confer known characteristics to the substrate. By manipulating the charge carried by the functionalized graphene oxides, the outgrowth and branching of neuronal processes can be controlled. Compared with neutral, zwitterionic, or negatively charged graphene oxides, positively charged graphene oxide was found to be more beneficial for neurite outgrowth and branching. The ability to chemically modify graphene oxide to control neurite outgrowth could be implemented clinically, especially in cases wherein long-term presence of outgrowth modulation is necessary.

Effects of surface charges of graphene oxide on neuronal outgrowth and branching

Monolayer-protected metal nanoparticles (MPMNs) are a newly discovered class of nanoparticles with an ordered, striped domain structure that can be readily manipulated by altering the ratio of the hydrophobic to hydrophilic ligands. This property makes them uniquely suited to systematic studies of the role of nanostructuring on biomolecule adsorption, a phenomenon of paramount importance in biomaterials design. In this work, we examine the interaction of the simple, globular protein cytochrome C (Cyt C) with MPMN surfaces using experimental protein assays and computational molecular dynamics simulations. Experimental assays revealed that adsorption of Cyt C generally increased with increasing surface polar ligand content, indicative of the dominance of hydrophilic interactions in Cyt C-MPMN binding. Protein-surface adsorption enthalpies calculated from computational simulations employing rigid-backbone coarse-grained Cyt C and MPMN models indicate a monotonic increase in adsorption enthalpy with respect to MPMN surface polarity. These results are in qualitative agreement with experimental results and suggest that Cyt C does not undergo significant structural disruption upon adsorption to MPMN surfaces. Coarse-grained and atomistic simulations furthermore elucidated the important role of lysine in facilitating Cyt C adsorption to MPMN surfaces. The amphipathic character of the lysine side chain enables it to form close contacts with both polar and nonpolar surface ligands simultaneously, rendering it especially important for interactions with surfaces composed of adjacent nanoscale chemical domains. The importance of these structural characteristics of lysine suggests that proteins may be engineered to specifically interact with nanomaterials by targeted incorporation of unnatural amino acids possessing dual affinity to differing chemical motifs.

Ordering Surfaces on the Nanoscale: Implications for Protein Adsorption

With the emergence of microscale biotechnology, such as biomicroelectromechanical systems (“Bio-MEMS”) and microfluidic-based microchips for sensing and diagnostics, polydimethylsiloxane (PDMS)-based elastomers have become very popular materials. PDMS elastomers possess several features that are well suited for these applications: mechanical stability and elasticity, chemical inertness, optical transparency, gas permeability, ease of fabrication, and biocompatibility. However, the extremely hydrophobic nature of PDMS often limits its applicability (e.g. poor aqueous fluid flow and nonspecific adhesion of biomolecules). Various methods have been proposed to modify the PDMS surface to impart hydrophilicity, for example, UV or plasma treatment to oxidize the surface and coating the surface with hydrophilic polymers. However, the treated PDMS surfaces often recover their hydrophobic traits due to the migration of unreacted PDMS oligomers to the surface and the rearrangement of PDMS polymer chains. We suggest that coating PDMS with hydrophilic materials would be more effective than the molecular level modifications. Hydrogels, which are networks of cross-linked polymers taking up large amounts of water, are therefore considered promising materials. Hydrogels can also be designed to present functionalities for specific purposes, such as in vitro cell culture, cell encapsulation, and molecular capture and release. Therefore, PDMS coated with hydrogels with desired properties would significantly enhance the performance of PDMS-based devices. However, it is a significant challenge to attain and sustain the adhesion between hydrogel and PDMS, due to the stark discrepancy between the bulk properties of PDMS substrates and hydrogels. To meet this challenge, we describe a unique approach to tailor hydrogel adhesion to a PDMS substrate. Alginate, a naturally derived polysaccharide, was covalently linked to the PDMS surface. This attached alginate acted as a “glue” to allow the strong, permanent adhesion of the hydrogel onto the PDMS surface by 1) imparting hydrophilicity to improve compatibility with hydrogels, and 2) providing functional groups for the stable conjugation of hydrogels. The resulting hydrogel-coated PDMS substrate was used in the following two applications: 1) it served as an in vitro cell culture platform to study cellular behavior in response to cyclic mechanical strain, and 2) it was used in a microfluidic device with hydrogel-filled channels. The PDMS surface was chemically grafted with alginate following a series of modification steps: step 1: oxidation to present hydroxy groups (OH-PDMS, Figure 1a); step 2: silanization using 3-aminopropyltriethoxysilane to present primary amino groups (NH2-PDMS); and step 3: conjugation of alginate by carbodiimide-mediated amide coupling between amino groups on the PDMS surface and carboxylic acid groups of alginate (alginate-PDMS). The successive modifications of PDMS were confirmed with FTIR spectroscopy (Figure S1 and Table S1 in the Supporting Information). The chemical linkage of alginate to the PDMS surface was further confirmed with fluorescently labeled alginate (Figure S2 in the Supporting Information). The decreased water contact angle of alginate-PDMS also showed that it is more hydrophilic than unmodified PDMS, OH-PDMS, and NH2-PDMS (Figure 1b). Next, alginate hydrogels were fabricated on the alginatePDMS by means of activating a covalent or an ionic crosslinking reaction. We thought that the alginate glue on the PDMS surface would participate in the reaction and hold the alginate hydrogel to the surface (Figure 2). First, an aqueous mixture of alginate and adipic acid dihydrazide (AAD) was placed on the alginate-PDMS, in order to fabricate the hydrogel by carbodiimide-mediated amide coupling. The resulting AAD-alginate hydrogel remained stably attached to alginate-PDMS for several months, regardless of the gel thickness, demonstrating that the alginate glue on the PDMS participated in the crosslinking reaction. No interfacial failure was observed between the bulk hydrogel and alginate-PDMS even when the construct was bent (Figure 3a). Alginate hydrogel crosslinked with calcium ions could also be prepared on alginate-PDMS. The resulting calciumalginate hydrogel also remained stably attached to the alginate-PDMS for several months. No interfacial failure [*] M. Lee, J. H. Jeong, Prof. H. Kong Department of Chemical and Biomolecular Engineering University of Illinois, Urbana, IL 61801 (USA) E-mail: hjkong06@illinois.edu

Tailoring Hydrogel Adhesion to Polydimethylsiloxane Substrates Using Polysaccharide Glue

An improved approach for the surface modification of poly(dimethylsiloxane) (PDMS) using carboxymethyl cellulose (CMC), carboxymethyl β-1,3-dextran (CMD), and alginic acid (AA) was investigated. The PDMS substrates were first oxidized in a H2SO4/H2O2 solution to transform the Si−CH3 groups on their surfaces into Si−OH groups. Then methacrylate groups were grafted onto the substrates through a silanization reaction using 3-(trimethoxysilyl)propyl methacrylate. Sequentially, cysteamine was conjugated onto the silanized surfaces by the reaction between the thiol and methacrylate groups under 254 nm UV exposure. Afterward, the amino-terminated PDMS substrates were sequentially reacted with CMC, CMD, and AA in the presence of N-hydroxysuccinimide and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, resulting in the grafting of polysaccharides onto PDMS surfaces. The composition and chemical state of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS). In addition, the stability a...

Liangliang Xin

Papers

Photocatalyzed surface modification of poly(dimethylsiloxane) with polysaccharides and assay of their protein adsorption and cytocompatibility.