The structure of temperature-sensitive poly(N-isopropylacrylamide) microgels in dilute suspension was investigated by means of small-angle neutron scattering. A direct modeling expression for the scattering intensity distribution was derived which describes very well the experimental data at all temperatures over an extensive q range. The overall particle form as well as the internal structure of the microgel network is described by the model. The influence of temperature, cross-linking density, and particle size on the structure was revealed by radial density profiles and clearly showed that the segment density in the swollen state is not homogeneous, but gradually decays at the surface. The density profile reveals a box profile only when the particles are collapsed at elevated temperatures. An increase of the cross-linking density resulted in both an increase of the polymer volume fraction in the inner region of the particle and a reduction of the smearing of the surface. The polymer volume fraction inside the colloid decreased with increasing particle size. The structural changes are in good agreement with the kinetics of the emulsion copolymerization used to prepare the microgel colloids.

We study how a cavity changes the response of hollow microgels with respect to regular ones in overcrowded environments. The structural changes of hollow poly(N-isopropylacrylamide) microgels embedded within a matrix of regular ones are probed by small-angle neutron scattering with contrast variation. The form factors of the microgels at increasing compressions are directly measured. The decrease of the cavity size with increasing concentration shows that the hollow microgels have an alternative way with respect to regular cross-linked ones to respond to the squeezing due to their neighbors. The structural changes under compression are supported by the radial density profiles obtained with computer simulations. The presence of the cavity offers to the polymer network the possibility to expand toward the center of the microgels in response to the overcrowded environment. Furthermore, upon increasing compression, a two step transition occurs: First the microgels are compressed but the internal structure is unchanged; then, further compression causes the fuzzy shell to collapse completely and reduce the size of the cavity. Computer simulations also allow studying higher compression degrees than in the experiments leading to the microgel's faceting.

in cell biology, [ 29,30 ] e.g., in cell signaling and protein expression. [31][32][33] For instance, it is reported that shear stress promotes maturation of megakaryocytes. [ 34 ] Moderate shear stress was found to have an infl uence on stem cell differentiation. [ 35 ] Excessive shear stress, in contrast, even dispatches cells by disrupting the membrane. These phenomena are even more crucial in bioprinting processes, where hydrogels of high viscosity and small nozzles are applied in an attempt to improve the fi nal printing resolution. Here, we show that both hydrogel viscosity and nozzle size directly affect shear stress. To prevent adverse cell response and printing-related cell death, it is essential to control the shear stress level, identify its most important drivers, and study the cell response upon different stress levels. We hypothesize that regulating shear stress and elucidating its impact would be of great use in balancing cell integrity and printing resolution.We present a microvalve-based bioprinting system for the manufacturing of high resolution, multi-material 3D structures ( Scheme 1 A). Applying a straightforward fl uid-dynamics model, we were able to precisely control shear stress at the nozzle site, which could be adjusted by varying the printing pressure, hydrogel viscosity, and the nozzle diameter. Using this system, we conducted a broad study on how cell viability and proliferation potential are affected by different levels of shear stress (Scheme 1 B). Generating complex, multi-material 3D-structures, we demonstrate that high-resolution printing at moderate, cell-friendly nozzle shear stress are not mutually exclusive.The printer used throughout this study comprised four microvalve-based print heads, each individually controllable and heatable, mounted to a three-axis robotic system ( Figure S1, Supporting Information). A metal stage that could be lowered into a container fi lled with a bi-phasic support liquid-perfl uorocarbon (PFC) and an aqueous crosslinker solution-was used as a printing platform that allowed for the manufacturing of macroscopic, multi-layered 3D structures ( Figure S1, Supporting Information). The presented printing system dispenses single drops of cell-hydrogel suspension by jetting using electromagnetic microvalves. Thus, cells are primarily exposed to mechanical stress in the form of shear stress. To describe the shear stress condition in the nozzle of the valve, we developed a fl uid dynamics model for transient fl ow of non-Newtonian fl uids (hydrogels) based on the Bernoulli equation for unsteady fl ow: Equation (

Microgels are macromolecular networks swollen by the solvent in which they are dissolved. They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called "nanogels"). In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. When swollen, they are soft and have a fuzzy surface with dangling chains. The presence of cross-links provides structural integrity, in contrast to linear and (hyper)branched polymers. Obviously, the cross-linker content will allow control of whether microgels behave more "colloidal" or "macromolecular". The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core-shell or hollow-two-shell morphology will display very different properties. Microgels provide the possibility to introduce chemical functionality at different positions. Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. The open microgel structure is beneficial for uptake-release purposes of active substances. In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. In sum, microgels unite properties of very different classes of materials. Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. This Account focuses on ...