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Functional Nanostructured Materials (including low-D carbon)
2.5D Hierarchical Structuring of Nanocomposite Hydrogel Films Containing Cellulose Nanocrystals Kevin J. De France, Mouhanad Babi, Jaana Vapaavuori, Todd Hoare, Jose M. Moran-Mirabal, and Emily D. Cranston ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.8b16232 • Publication Date (Web): 22 Jan 2019 Downloaded from http://pubs.acs.org on January 25, 2019
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ACS Applied Materials & Interfaces
2.5D Hierarchical Structuring of Nanocomposite Hydrogel Films Containing Cellulose Nanocrystals Kevin J. De France†, Mouhanad Babi‡, Jaana Vapaavuoriξ, Todd Hoare†, Jose Moran-Mirabal‡*, Emily D. Cranston†, δ, λ*
†
Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada
‡
Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4M1, Canada
ξ
Department of Chemistry, University of Montreal, C.P. 6128 Succursale Centre-ville, Montreal, QC, Canada H3C 3J7
δ
Department of Wood Science, University of British Columbia, 2424 Main Mall, Vancouver, BC, V6T 1Z4, Canada
λ
Department of Chemical and Biological Engineering, University of British Columbia, 2360 East Mall, Vancouver, BC V6T 1Z3, Canada
Corresponding Author *E-mail:
[email protected],
[email protected] Keywords: cellulose nanocrystals, structured hydrogels, thin film hydrogels, wrinkling, hierarchical wrinkles
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ABSTRACT While 2D hydrogel thin films have been applied across many biomedical applications, creating higher dimensionality structured hydrogel interfaces would enable potentially improved and more biomimetic hydrogel performance in biosensing, bioseparations, tissue engineering, drug delivery, and wound healing applications. Herein we present a new and simple approach to control the structure of hydrogel thin films in 2.5D. Hybrid suspensions containing cellulose nanocrystals (CNCs) and aldehyde- or hydrazide-functionalized poly(oligoethylene glycol methacrylate) (POEGMA) were spin coated onto pre-stressed polystyrene substrates to form crosslinked hydrogel thin films. The films were then structured via thermal shrinking, with control over the direction of shrinking leading to the formation of biaxial, uniaxial, or hierarchical wrinkles. Notably, POEGMA-only hydrogel thin films (without CNCs) did not form uniform wrinkles due to partial de-wetting from the substrate during shrinking. Topographical feature sizes of CNCPOEGMA films could be tuned across two orders of magnitude (from ~300 nm to 20 µm) by varying the POEGMA concentration, the length of polyethylene glycol side chains in the polymer, and/or the overall film thickness. Furthermore, by employing adhesive masks during the spin coating process, structured films with gradient wrinkle sizes can be fabricated. This precise control over both wrinkle size and wrinkle topography adds a level of functionality that to date has been lacking in conventional hydrogel networks.
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ACS Applied Materials & Interfaces
INTRODUCTION Due to their hydrophilic nature, generally good biocompatibility, and tunable composition, hydrogels have been a central focus in the fields of biomaterials science and biomedical engineering for the past few decades.1 Recently, there has been an increased interest in the 3D structuring/patterning of hydrogels in order to more accurately model cell-matrix interactions, encapsulate cells, and design functional scaffolds for tissue engineering, among a range of other applications.2–6 However, there has been significantly less research focusing on the structuring of 2D hydrogel thin films. The ability to make surface features, control feature size, and increase interfacial surface area to enhance the interactions between a hydrogel and its environment and/or modify the rate of a hydrogel’s response to its environment, would be a promising development in this field. Such materials could find potential applications in thin film tissue engineering,7 bioseparations,8 biosensing,9 actuating,9,10 and flexible electronics.11,12 Here, we demonstrate a simple thermal shrinking approach to induce micro- and nanostructured topographies in nanocomposite hydrogel films in 2.5D, composed of cellulose nanocrystals (CNCs, a hydrophilic and colloidally stable rigid rod-shaped bio-based nanomaterial with high strength and high surface area)13–17 and poly(oligoethylene glycol methacrylate) (POEGMA, a versatile synthetic thermoresponsive polyethylene glycol-based polymer with excellent antifouling properties).18–22 Traditionally, thermal shrinking has been used to prepare micro- and nanostructured metallic, oxide and carbon nanotube thin films with tunable wrinkle wavelengths.23–26 Recent work in our lab has shown the applicability of this technique to structure organic polymer and polymer nanocomposite films assembled using water-based processing methods;27,28 however, to date this technique has not been demonstrated for the fabrication of structured hydrogels or to create hierarchical structures by sequential shrinking steps.
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The wrinkling technique employed works by depositing a thin film on top of a pre-stressed polystyrene substrate and subsequently heating the sample above the glass transition temperature (Tg) of polystyrene, causing the substrate to shrink. The stiffness mismatch between the soft underlying polystyrene and rigid thin film induces a buckling in the thin film in order to dissipate built-up stress.29 The resulting feature sizes can be controlled by varying the thickness of the deposited film, with thicker (and thus stiffer) films leading to larger observed wrinkle sizes due to the increase in mechanical mismatch between the substrate and the film.29 There are currently only a few published methods for preparing structured thin film hydrogels, almost all of which employ UV-mediated gelation and small molecule crosslinkers for film curing.30 Physical templating methods such as microcontact printing31–34 and soft embossing/contact lithography,35–38 have demonstrated some success; however, these techniques require additional fabrication steps to prepare molds and typically yield hydrogels with limited feature size resolution and weak mechanical properties. Photolithography has also been used, although feature size resolution is limited by the photomask construction.39–43 It should be noted that high energy irradiation techniques such as electron beam patterning have been demonstrated to improve feature size resolution below the tens of microns length scale; however, the achieved improvements in feature size resolution are offset by the lengthier and more complicated preparation process as well as limitations to the thickness of the film etched (typically to a maximum of hundreds of nanometers).44–47 Finally, hydrogels with swelling-induced wrinkling patterns have been prepared by photopolymerizing a hydrogel film affixed on top of a rigid substrate;48–51 as the surface-attached hydrogel layer swells, wrinkles on the order of hundreds of microns are formed as a mechanism of stress dissipation.48–50 However, due to the necessity for photopolymerization and the inherently limited mechanical properties of most hydrogels, the
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ACS Applied Materials & Interfaces
currently reported structured thin film hydrogel preparation methods are highly limited in terms of both feature size resolution and shape fidelity. Thermal shrinking of hydrogels has not previously been demonstrated and offers a new strategy to achieve a range of precise surface morphologies without multi-step protocols, expensive equipment, or additional chemical components. Toward the goal of increasing hydrogel moduli to improve feature size resolution and fidelity, we have recently reported mechanically-enhanced and 3D structured CNC-POEGMA nanocomposite hydrogels that are promising tissue engineering scaffolds.52–54 Herein, we aim to utilize this knowledge to demonstrate that thin film hydrogels can be structured through thermal shrinking. Our “2.5D hydrogels” (i.e., swellable crosslinked thin films with some structural morphology in the z-direction) are fabricated following a simple and straightforward method and have controllable feature sizes, unique morphologies, and nanoscale resolution.
RESULTS & DISCUSSION Preparation of CNC-POEGMA Thin Film Hydrogels In our lab, POEGMA hydrogels are typically prepared by reactive coextrusion whereby precursor polymers functionalized with hydrazide and aldehyde functionalized groups are coextruded to form injectable hydrogels crosslinked via hydrolytically-degradable hydrazone bonds.21,55 The crosslink density (mesh size) can be varied from low (~ 5 × 1017 cm-3) to high (~ 20 × 1017 cm-3) by incorporating OEGMA monomers with different polyethylene glycol (PEG) side chain lengths which sterically interfere with hydrazone crosslinking.22 Similarly, gelation time can be varied from ~ 45 min to
