Macroporous-Enabled Highly Deformable Layered Hydrogels with Designed pH Response.

Environment-responsive hydrogel structures are of great interest in materials research and have a wide range of applications. By using a flow lithography technique, we report a one-step and high-throughput fabrication method for the synthesis of highly pH-responsive hydrogels with designed shape transformations. In this method, heterogeneous hydrogels with porous and nonporous layers are synthesized using a single UV exposure in a microfluidic channel. During the UV polymerization, the porous layers, which are formed by using polymerization-induced phase separation (PIPS), significantly increase the swelling capability and enhance the swelling rate of the hydrogels. Because the flow-lithography approach allows various patterns of porous/nonporous layers with great control and enables the simple integration of PIPS, resultant layered hydrogels show extraordinary deformations with desired pH response. More importantly, our fabrication approach can not only make 2D deformation of hydrogel structures such as bending but also can achieve 3D structural deformation such as helical and buckling structures, enabled by nonuniform UV polymerization we developed.

Fabrication of Highly Porous Nonspherical Particles Using Stop-Flow Lithography and the Study of Their Optical Properties.

A microfluidic flow lithography approach was investigated to synthesize highly porous nonspherical particles and Janus particles in a one-step and high-throughput fashion. In this study, using common solvents as porogens, we were able to synthesize highly porous particles with different shapes using ultraviolet (UV) polymerization-induced phase separation in a microfluidic channel. We also studied the pore-forming process using operating parameters such as porogen type, porogen concentration, and UV intensity to tune the pore size and increase the pore size to submicron levels. By simply coflowing multiple streams in the microfluidic channel, we were able to create porous Janus particles; we showed that their anisotropic swelling/deswelling exhibit a unique optical shifting. The distinctive optical properties and the enlarged surface area of the highly porous particles can improve their performance in various applications such as optical sensors and drug loading.

Precision-Trimming 2D Inverse-Opal Lattice on Elastomer to Ordered Nanostructures with Variable Size and Morphology.

A low-cost and scalable method is developed for producing large-area elastomer surfaces having ordered nanostructures with a variety of lattice features controllable to nanometer precision. The method adopts the known technique of molding a PDMS precursor film with a close-packed monolayer of monodisperse submicron polystyrene beads on water to form an inverse-opal dimple lattice with the dimple size controlled by the bead selection and the dimple depth by the molding condition. The subsequent novel precision engineering of the inverse-opal lattice comprises trimming the PDMS precursor by a combination of polymer curing temperature/time and polymer dissolution parameters. The resultant ordered surface nanostructures, fabricated with an increasing degree of trimming, include (a) submicron hemispherical dimples with nanothin interdimple rims and walls; (b) nanocones with variable degrees of tip-sharpness by trimming off the top part of the nanothin interdimple walls; and (c) soup-plate-like submicron shallow dimples with interdimple rims and walls by anisotropically trimming off the nanocones and forming close-packed shallow dimples. As exemplars of industrial relevance of these lattice features, tunable Young's modulus and wettability are demonstrated.

Functional polymer sheet patterning using microfluidics.

Poly(dimethylsiloxane) (PDMS)-based microfluidics provide a novel approach to advanced material synthesis. While PDMS has been successfully used in a wide range of industrial applications, due to the weak mechanical property channels generally possess low aspect ratios (AR) and thus produce microparticles with similarly low ARs. By increasing the channel width to nearly 1 cm, AR to 267, and implementing flow lithography, we were able to establish the slit-channel lithography. Not only does this allow us to synthesize sheet materials bearing multiscale features and tunable chemical anisotropy but it also allows us to fabricate functional layered sheet structures in a one-step, high-throughput fashion. We showcased the technique's potential role in various applications, such as the synthesis of planar material with micro- and nanoscale features, surface morphologies, construction of tubular and 3D layered hydrogel tissue scaffolds, and one-step formation of radio frequency identification (RFID) tags. The method introduced offers a novel route to functional sheet material synthesis and sheet system fabrication.

Wrinkling Non-Spherical Particles and Its Application in Cell Attachment Promotion.

Surface wrinkled particles are ubiquitous in nature and present in different sizes and shapes, such as plant pollens and peppercorn seeds. These natural wrinkles provide the particles with advanced functions to survive and thrive in nature. In this work, by combining flow lithography and plasma treatment, we have developed a simple method that can rapidly create wrinkled non-spherical particles, mimicking the surface textures in nature. Due to the oxygen inhibition in flow lithography, the non-spherical particles synthesized in a microfluidic channel are covered by a partially cured polymer (PCP) layer. When exposed to plasma treatment, this PCP layer rapidly buckles, forming surface-wrinkled particles. We designed and fabricated various particles with desired shapes and sizes. The surfaces of these shapes were tuned to created wrinkle morphologies by controlling UV exposure time and the washing process. We further demonstrated that wrinkles on the particles significantly promoted cell attachment without any chemical modification, potentially providing a new route for cell attachment for various biomedical applications.

Effect of needle geometry on flow rate and cell damage in the dispensing-based biofabrication process.

Biodispensing techniques have been widely applied in biofabrication processes to deliver cell suspensions and biomaterials to create cell-seeded constructs. Under identical operating conditions,two types of dispensing needles­tapered and cylindrical­can result in different flow rates of material and different cell damage percent induced by the mechanical forces. In this work, mathematical models of both flow rate and cell damage percent in biodispensing systems using tapered and cylindrical needles, respectively, were developed, and experiments were carried out to verify the effectiveness of the developed models. Both simulations and experiments show tapered needles produce much higher flow rates under the same pressure conditions than cylindrical needles. Use of a lower pressure in a tapered needle can therefore achieve the same flow rate as that in a cylindrical needle. At equivalent flow rates, cell damage in a tapered needle is lower than that in a cylindrical one. Both Schwann cells and 3T3 fibroblasts, which have been widely used in tissue engineering, were used to validate the cell damage models. Application of the developed models to specify the influence of process parameters, including needle geometry and air pressure, on the flow rate and cell damage percent represents a significant advance for biofabrication processes.The models can be used to optimize process parameters to preserve cell viability and achieve the desired cell distribution in dispensing-based biofabrication.

Modeling process-induced cell damage in the biodispensing process.

Emerging biomanufacturing processes involve incorporation of living cells into various processes and systems by employing different cell manipulation techniques. Among them, biodispensing, in which the cell suspension is extruded via a fine needle under pressurized air, is a promising technique because of its high efficiency. Cells in this process are continually subjected to mechanical forces and may be damaged if the force or manipulation time exceeds certain levels. Modeling cell injury incurred in these processes is lacking in the literature. This article presents a method to quantify the force-induced cell damage in the biodispensing process. This method consists of two steps: first is to establish cell damage laws to relate cell damage to hydrostatic pressure/shear stress; and the second is to represent the process-induced forces experienced by cells during the biodispensing process and apply the established cell damage law to represent the percentage of cell damage. Schwann cells and 3T3 fibroblasts were used to validate the model and the comparisons of experimental and simulation results show the effectiveness of the method presented in this article.