Thermally Assisted Microfluidics to Produce Chemically Equivalent Microgels with Tunable Network Morphologies.

Although micron-sized microgels have become important building blocks in regenerative materials, offering decisive interactions with living matter, their chemical composition mostly significantly varies when their network morphology is tuned. Since cell behavior is simultaneously affected by the physical, chemical, and structural properties of the gel network, microgels with variable morphology but chemical equivalence are of interest. This work describes a new method to produce thermoresponsive microgels with defined mechanical properties, surface morphologies, and volume phase transition temperatures. A wide variety of microgels is synthesized by crosslinking monomers or star polymers at different temperatures using thermally assisted microfluidics. The diversification of microgels with different network structures and morphologies but of chemical equivalence offers a new platform of microgel building blocks with the ability to undergo phase transition at physiological temperatures. The method holds high potential to create soft and dynamic materials while maintaining the chemical composition for a wide variety of applications in biomedicine.

Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake.

Cellular internalization of inorganic, lipidic and polymeric nanoparticles is of great significance in the quest to develop effective formulations for the treatment of high morbidity rate diseases. Understanding nanoparticle-cell interactions plays a key role in therapeutic interventions, and it continues to be a topic of great interest to both chemists and biologists. The mechanistic evaluation of cellular uptake is quite complex and is continuously being aided by the design of nanocarriers with desired physico-chemical properties. The progress in biomedicine, including enhancing the rate of uptake by the cells, is being made through the development of structure-property relationships in nanoparticles. We summarize here investigations related to transport pathways through active and passive mechanisms, and the role played by physico-chemical properties of nanoparticles, including size, geometry or shape, core-corona structure, surface chemistry, ligand binding and mechanical effects, in influencing intracellular delivery. It is becoming clear that designing nanoparticles with specific surface composition, and engineered physical and mechanical characteristics, can facilitate their internalization more efficiently into the targeted cells, as well as enhance the rate of cellular uptake.

Annealing High Aspect Ratio Microgels into Macroporous 3D Scaffolds Allows for Higher Porosities and Effective Cell Migration.

Growing millimeter-scaled functional tissue remains a major challenge in the field of tissue engineering. Therefore, microporous annealed particles (MAPs) are emerging as promising porous biomaterials that are formed by assembly of microgel building blocks. To further vary the pore size and increase overall MAP porosity of mechanically stable scaffolds, rod-shaped microgels with high aspect ratios up to 20 are chemically interlinked into highly porous scaffolds. Polyethylene glycol based microgels (width 10 µm, lengths up to 200 µm) are produced via in-mold polymerization and covalently interlinked into stable 3D scaffolds via epoxy-amine chemistry. For the first time, MAP porosities can be enhanced by increasing the microgel aspect ratio (mean pore sizes ranging from 39 to 82 µm, porosities from 65 to 90%). These porosities are significantly higher compared to constructs made from spherical or lower aspect ratio rod-shaped microgels. Rapid filling of the pores by either murine or primary human fibroblasts is ensured as cells migrate and grow extensively into these scaffolds. Overall, this study demonstrates that highly porous, stable macroporous hydrogels can be achieved with a very low partial volume of synthetic, high aspect ratio microgels, leading to large empty volumes available for cell ingrowth and cell-cell interactions.