Cargo shuttling by electrochemical switching of core-shell microgels obtained by a facile one-shot polymerization.

Controlling and understanding the electrochemical properties of electroactive polymeric colloids is a highly topical but still a rather unexplored field of research. This is especially true when considering more complex particle architectures like stimuli-responsive microgels, which would entail different kinetic constraints for charge transport within one particle. We synthesize and electrochemically address dual stimuli responsive core-shell microgels, where the temperature-responsiveness modulates not only the internal structure, but also the microgel electroactivity both on an internal and on a global scale. In detail, a facile one-step precipitation polymerization results in architecturally advanced poly(N-isopropylacrylamide-co-vinylferrocene) P(NIPAM-co-VFc) microgels with a ferrocene (Fc)-enriched (collapsed/hard) core and a NIPAM-rich shell. While the remaining Fc units in the shell are electrochemically accessible, the electrochemical activity of Fc in the core is limited due to the restricted mobility of redox active sites and therefore restricted electron transfer in the compact core domain. Still, prolonged electrochemical action and/or chemical oxidation enable a reversible adjustment of the internal microgel structure from core-shell microgels with a dense core to completely oxidized microgels with a highly swollen core and a denser corona. The combination of thermo-sensitive and redox-responsive units being part of the network allows for efficient amplification of the redox response on the overall microgel dimension, which is mainly governed by the shell. Further, it allows for an electrochemical switching of polarity (hydrophilicity/hydrophobicity) of the microgel, enabling an electrochemically triggered uptake and release of active guest molecules. Hence, bactericidal drugs can be released to effectively kill bacteria. In addition, good biocompatibility of the microgels in cell tests suggests suitability of the new microgel system for future biomedical applications.

Screening Platform for Cell Contact Guidance Based on Inorganic Biomaterial Micro/nanotopographical Gradients.

High-throughput screening (HTS) methods based on topography gradients or arrays have been extensively used to investigate cell-material interactions. However, it is a huge technological challenge to cost efficiently prepare topographical gradients of inorganic biomaterials due to their inherent material properties. Here, we developed a novel strategy translating PDMS-based wrinkled topography gradients with amplitudes from 49 to 2561 nm and wavelengths between 464 and 7121 nm to inorganic biomaterials (SiO2, Ti/TiO2, Cr/CrO3, and Al2O3) which are frequently used clinical materials. Optimal substratum conditions promoted human bone-marrow derived mesenchymal stem cell alignment, elongation, cytoskeleton arrangement, filopodia development as well as cell adhesion in vitro, which depended both on topography and interface material. This study displays a positive correlation between cell alignment and the orientation of cytoskeleton, filopodia, and focal adhesions. This platform vastly minimizes the experimental efforts both for inorganic material interface engineering and cell biological assessments in a facile and effective approach. The practical application of the HTS technology is expected to aid in the acceleration of developments of inorganic clinical biomaterials.

Anti-Microbial Biopolymer Hydrogel Scaffolds for Stem Cell Encapsulation.

Biopolymer hydrogels are an attractive class of materials for wound dressings and other biomedical applications because of their ease of use and availability from biomass. Here, we present a hydrogel formation approach based on alginate and chitosan. Alginate is conventionally cross-linked using multivalent ions such as Ca2+ but in principle any polycationic species can be used such as polyelectrolytes. Exchanging the cross-linking Ca2+ ions partially with chitosan, which at pH 7 has available positive charges as well as good interactions with Ca2+, leads to an improved Young's modulus. This gel is non-toxic to mammalian cells and hence allows conveniently for stem cell encapsulation since it is based on two-component mixing and gel formation. Additionally, the chitosan is known to have a bactericidal effect which is retained when using it in the alginate⁻chitosan gel formation and the formed hydrogels displayed bactericidal effects against P. aeruginosa and S. aureus. The combination of anti-bacterial properties, inclusion of stem cells, and the hydrogel nature would provide an ideal environment for complex wound healing.

Non-Covalently Stabilized Alginate Hydrogels as Functional Cell Scaffold Material.

Biopolymers are an attractive class of compounds for being used in biomedical applications as they are widely available from biomass. Their drawback is the lack of mechanical stability and the ability to tune this properly. Covalent chemical cross-linking is an often used approach but it limits usability due to legislation as well as the need of advanced and specialized knowledge by end users such as clinicians. Here, increased and tunable mechanical properties are achieved of alginate-based hydrogels with non-covalent approaches using linear polyethyleneimine (LPEI) as a polyelectrolyte rather than only multivalent metal ions (Ca2+ ). Gel stiffness increases with increasing LPEI content. Gel morphology changes from a thin fibrous mesh for alginate-Ca2+ to thicker fibrous networks when LPEI is introduced. The gels are able to efficiently release encapsulated small molecular dyes and the gels are able to host cells. For the cell encapsulation human skin fibroblasts (HSkF) and human bone marrow-derived mesenchymal stem cells (hBM-MSC) are used. HSkF can be successfully incorporated without diminished viability while the matrix components and gel preparation method are not compatible with hBM-MSC. The newly developed alginate-based system is regarded as a potential candidate for wound dressing materials.

Directional nanotopographic gradients: a high-throughput screening platform for cell contact guidance.

A novel approach was developed using PDMS-substrates with surface-aligned nanotopography gradients, varying unidirectional in amplitude and wavelength, for studying cell behavior with regard to adhesion and alignment. The gradients target more surface feature parameters simultaneously and provide more information with fewer experiments and are therefore vastly superior with respect to individual topography substrates. Cellular adhesion experiments on non-gradient aligned nanowrinkled surfaces displayed a linear relationship of osteoblast cell adhesion with respect to topography aspect ratio. Additionally, an aspect ratio of 0.25 was found to be most efficient for cell alignment. Modification of the surface preparation method allowed us to develop an approach for creating surface nanotopography gradients which innovatively provided a superior data collection with fewer experiments showing that 1) low amplitude with small wavenumber is best for osteoblast cell adhesion 2) indeed higher aspect ratios are favorable for alignment however only with features between 80-180 nm in amplitude and 450-750 nm in wavelength with a clear transition between adhesion and alignment efficiency and 3) disproved a linear relationship of cell adhesion towards aspect ratio as was found for single feature substrate analysis.

Directed Autonomic Flow: Functional Motility Fluidics.

Unidirectional coherent motion of a self-moving droplet is achieved and combined in a functional motility fluidic chip for chemical reactions via a novel and straightforward approach. The droplet shows both increased movement speeds and displacement distances without any input of energy. Nanoparticle synthesis is performed using the autonomous movement in a fluidic chip that induces transport, mixing, and collection.