Multi-responsive hydrogel structures from patterned droplet networks

Abstract

Responsive hydrogels that undergo controlled shape changes in response to a range of stimuli are of interest for microscale soft robotic and biomedical devices. However, these applications require fabrication methods capable of preparing complex, heterogeneous materials. Here we report a new approach for making patterned, multi-material and multi-responsive hydrogels, on a micrometre to millimetre scale. Nanolitre aqueous pre-gel droplets were connected through lipid bilayers in predetermined architectures and photopolymerized to yield continuous hydrogel structures. By using this droplet network technology to pattern domains containing temperature-responsive or non-responsive hydrogels, structures that undergo reversible curling were produced. Through patterning of gold nanoparticle-containing domains into the hydrogels, light-activated shape change was achieved, while domains bearing magnetic particles allowed movement of the structures in a magnetic field. To highlight our technique, we generated a multi-responsive hydrogel that, at one temperature, could be moved through a constriction under a magnetic field and, at a second temperature, could grip and transport a cargo.

Figure 1. Multi-responsive hydrogel structures templated by droplet networks.

a-d, Schematic of the fabrication process for a hydrogel structure templated by a droplet pair. a, Pre-gel droplets are submerged in a lipid-containing oil and acquire lipid monolayer coatings. b, When the two droplets are brought together, a lipid bilayer forms at the interface between them. c, Photopolymerization results in the rupture of the bilayer, and formation of a continuous hydrogel structure. d, Droplet-templated hydrogel structures can be transferred into an aqueous environment. e, Different pre-gels, with the additives PEGDAAm, gold nanoparticles (AuNPs) or magnetic nickel particles, can be encapsulated in individual compartments of a droplet network. f, After polymerization, several types of stimulus-responsive hydrogel are integrated into a single patterned structure. g, Schematic showing the assembly of a pre-gel droplet network with 10 droplets from two different pre-gels by placement with a syringe. Insets show views of the assembly process from above.

Figure 2. Formation and temperature response of PNIPAm hydrogel structures templated with droplet networks.

a, Brightfield images of a NIPAm pre-gel-containing droplet pair in oil. After UV photopolymerization, a continuous hydrogel structure was formed. The structure was transferred into water and reversible isotropic contraction occurred at 42°C, above the LCST of PNIPAm. b-d, A three-droplet chain (b), three-droplet triangle (c) and four-droplet pyramid (d) were also fabricated and reversibly contracted at 42°C. Structures appear black upon heating above the LCST, due to an increase in the refractive index of PNIPAm. e, Four cycles of heating and cooling were performed for the droplet pair-, chain- and triangle-templated structures. The radii of droplets comprising these structures were measured at 25°C and 42°C, and normalised to their initial radii. The resulting mean shrinkage ratios are shown for each temperature across the cycles. The break in the x axis indicates that two cycles were performed on the structures on two different days. The dark green dotted line delineates the fully swollen structure, whereas the pale green dotted line delineates the fully contracted structure. f, Radii of 3 individual, non-connected PNIPAm droplets measured during contraction, while heating to 42°C, and reswelling, while cooling to room temperature. Error bars in (e) and (f) represent one standard deviation about the mean shrinkage ratio or the radius, respectively. Scale bars correspond to 250 μm.

Figure 3. Patterned fluorescent PNIPAm hydrogel structures.

(a) Overlaid brightfield and fluorescence microscopy images of hexagonal hydrogel structures patterned with a fluorescent crosslinker, EBBA. Scale bars correspond to 500 μm. (b) Overlaid brightfield and fluorescence microscopy images, and pixel intensity plot profiles (along the black dashed lines) of fluorescent hexagonal hydrogel structures, before and after heating to 42°C. The pixel intensity increase is due to an increase in local EBBA concentration as a result of temperature-induced contraction. Scale bars correspond to 250 μm.

Figure 4. Shape changes of structures containing two different temperature-responsive hydrogels.

a. A hydrogel structure formed from a droplet pair. One domain contained PNIPAm (white sphere) crosslinked with MBA, and the other in addition contained 8 mM PEGDAAm (n = 80, M_n = 3700) (orange sphere). When heated to 42°C, the PEGDAAm-PNIPAm domain contracted to a lesser extent than the PNIPAm domain (dark grey sphere). Scale bar corresponds to 250 μm. b-c, Larger structures patterned with PNIPAm and PEGDAAm-PNIPAm underwent pre-defined, temperature-controlled, reversible shape changes. A bilayer structure (b) formed from a parallel double strip of droplets with different crosslinkers curls when heated above the LCST of the MBA-containing hydrogel, whereas an alternating bilayer with a central point of inflection (c) undergoes a double curling motion. Scale bars correspond to 1 mm. d, Kinetics of curvature changes for the structure depicted in (c) during heating to 42°C (pale orange) and cooling to room temperature (white). Error bars represent one standard deviation about the mean curvature.

Figure 5. Shape changes of structures containing light-responsive domains.

a. PNIPAm structures containing embedded gold nanoparticles (AuNP-PNIPAm) contract when illuminated with green light (λ = 530 nm). b, Selective light-activated contraction of domains in a AuNP-PNIPAm hydrogel structure by using an aperture-restricted green light source. c, Two modes of deformation of a structure containing PNIPAm (white spheres) and AuNP-PNIPAm (pink spheres) domains. The structure contracts isotropically when heated to 42°C, and curls when irradiated with green light at 25°C. Scale bars correspond to 250 μm. Green dotted circles represent the regions of the structures irradiated with green light in b and c.

Figure 6. A magnetically- and dual temperature-responsive shape-changing structure.

a, Temperature dependence of the shrinkage ratio of PNIPAm hydrogel droplets (pale green squares), or droplets containing in addition 1 mM (pink circles) or 3 mM PEGDAAm (dark green triangles). Error bars indicate one standard deviation about the mean shrinkage ratio. b, Design of the multi-responsive shape-changing structure. The low LCST domain contained 0.4 mM PEGDAAm, while the high LCST domain contained 3.5 mM PEGDAAm. A magnetic handle in the low LCST domain contained MagneHis™ Ni-Particles. Initially, the hydrogel structure is trapped in chamber (1). After heating to 60°C, both domains of the structure contract and it can be pulled through a narrow channel by a magnetic field (2). Once in the central chamber, it is cooled to 35°C and becomes curled as the low LCST domain contracts (3). When heated once more to 60°C, it again contracts and can be magnetically pulled through a channel (4) into the final chamber. Here, the hydrogel is cooled to room temperature and returns to its original size and shape (5). Green lines indicate where the temperature has been changed. (c) Temperature dependence of the curvature of the fabricated multi-responsive shape-changing structure. Error bars indicate one standard deviation about the mean curvature of three structures. (d) Brightfield images of the dual-controlled shape-changing structure at positions (1)-(5). Green lines indicate the change in temperature, as well as where images are stitched together. Scale bar corresponds to 500 μm. See Supplementary Figure 10 for uncropped individual images.

Figure 7. Cargo transport and maze navigation by a magnetically responsive and dual temperature-responsive hydrogel gripper.

1. The gripper, initially outside the entrance to the maze, is fully contracted by heating it to 60°C. The fully contracted gripper can be pulled through a narrow channel at the entrance using a magnetic field. 2. Once inside the maze, it is cooled to room temperature, causing it to swell and straighten, before being heated to 42°C, allowing it to grip a cargo (coloured red). The cargo was a large PNIPAm hydrogel droplet containing AuNPs to improve visibility and PEGDAAm to minimise contraction at the temperature ranges used. 3. With the cargo in its grip, it is transported to the other end of the maze using a magnetic field. 4. Upon reaching the end of the maze, it is cooled to room temperature so that it releases the cargo. 5. The gripper is subsequently fully contracted at 60°C so that it can be pulled through the narrow channel at the exit of the maze. 6. The gripper reswells at room temperature. The images from each location have been stitched together to demonstrate the full path. Scale bar corresponds to 4 mm. See Supplementary Figure 12 for cargo transport and navigation through a more complex maze by a magnetically responsive and dual temperature-responsive hydrogel gripper. See Supplementary Figure 13 and 14 for a reproduction of the composite image with borders of stitched images indicated and uncropped individual images, respectively.