Tailoring Hydrogel Adhesion to Polydimethylsiloxane Substrates Using Polysaccharide Glue

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