Controlled origami folding of hydrogel bilayers with sustained reversibility for robust microcarriers.

Microencapsulation and controlled release have long been studied because of the high demand for practical delivery systems in the pharmaceutics and cosmetics fields. Multiphase emulsion drops have provided efficient templates for microcapsules, and various feasible methods have been developed for controlled release. However, the emulsion-based approach has limitations for the in situ control of membrane permeability. Micro-origami has emerged as one of the most promising alternative approaches for producing tunable microcapsules with the potential to be applied, for example as drug carriers, actuators, microcontainers, and microrobots. Inspired by living organisms in nature such as the ice plant and Venus flytrap, two different micro-origami approaches have been employed to make various microstructures. One approach uses solid patches connected by active hinge materials. Typical examples use various metal– metal, metal–polymer, and polymer–polymer combinations. The patch and hinge system has enabled the capture, release, and gripping of target materials, showing the feasibility of micro-origami structures. However, the microcapsule is limited to polyhedral shapes in this approach, and complete sealing of the gaps between patches requires exquisite control of the folding angles. Moreover, the delicate and complex fabrication processes make practical applications difficult. The second approach uses a bilayer structure composed of two different materials. For example, a metal– polymer bilayer can show bending/unbending when the polymeric active layer suffers significant volume change, but the metal layer remains unchanged. Polymer materials have been employed in both layers to make biocompatible microcapsules. However, complete sealing of the gaps in the bilayer contact regions remains an important, yet unmet, need. In addition, a simple and effective method for the fabrication of practical microcapsules has not yet been developed, and remains highly desirable. This is the main thrust of the present study. Herein, we report the use of biocompatible bilayer structures for the fabrication of tunable microcapsules based on micro-origami. Monodisperse bilayer microstructures were prepared using a facile photolithographic procedure, without employing photomask alignment. In addition, highly flexible hydrogels were selected as both active and passive layers, facilitating tight contact between patches. The bilayer structure therefore enabled in situ encapsulation, through a reversible transformation to microcapsules with a closed compartment. The resultant microcapsules showed negligible leakage of encapsulants and triggered release of the encapsulants could be achieved simply by inducing the unfolding of the hydrogel bilayer. The essential strategy of our approach relies on the anisotropic volume change of a hydrogel bilayer. As shown in Scheme 1a, the active hydrogel layer shows significant volume expansion under external stimuli by swelling, whereas the passive hydrogel layer remains in a constant volume. Therefore, mechanical stress drives the bending of the bilayer, resulting in microcapsules with a closed compartment. The hydrogel swelling behavior is highly reversible, enabling repeated transformations. The hydrogel bilayer structure was prepared on a glass substrate, using photolithography with an amorphous silicon photomask, as shown in Scheme 1b. Here, we propose poly(2hydroxyethyl methacrylate-co-acrylic acid), p(HEMA-coAA), and poly(2-hydroxyethyl methacrylate), p(HEMA), as model components because they are widely used, FDAapproved (FDA=Food and Drug Administration) biocompatible materials. One monomer solution for p(HEMA-coAA) was infiltrated into the space between the photomask and a polydimethylsiloxane (PDMS) microchannel of 25 mm thickness; this monomer solution was then polymerized by UV irradiation through the photomask. The second monomer solution for p(HEMA) was infiltrated into the space between the same photomask and a PDMS microchannel 50 mm in thickness, after washing out the previously unpolymerized solution. Upon the second round of UV irradiation, bilayer structures consisting of a p(HEMA) layer on a p(HEMA-coAA) layer were formed; alignment of the photomask was unnecessary, because each layer was fabricated on the photomask. The resultant bilayer structures were released from the photomask through immersion in a pH 9 buffer solution. To exploit the structural transformation of the bilayer microparticles, we used two different shapes of microparticle: snowman-shaped and flower-shaped. The shape and dimensions of these microparticles were carefully determined to ensure a fully closed compartment in the swollen state; both the snowmanand flower-shaped microparticles were 50 mm [*] T. S. Shim, Dr. S.-H. Kim, Dr. C.-J. Heo, H. C. Jeon, Prof. S.-M. Yang National Creative Research Initiative Center for Integrated Optofluidic Systems and Department of Chemical and Biomolecular Engineering KAIST Daejeon, 305-701 (Korea) E-mail: [email protected] Homepage: http://msfl.kaist.ac.kr