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Publication: Pathway-controlled formation of mesostructured all-DNA colloids and superstructures

Abstract: DNA has traditionally been used for the programmable design of nanostructures by exploiting its sequence-defined supramolecular recognition. However, control on larger length scales or even hierarchical materials that translate to the macroscale remain difficult to construct. Here, we show that the polymer character of single-stranded DNA (ssDNA) can be activated via a nucleobase-specific lower critical solution temperature, which provides a unique access to mesoscale structuring mechanisms on larger length scales. We integrate both effects into ssDNA multiblock copolymers that code sequences for phase separation, hybridization and functionalization. Kinetic pathway guidance using temperature ramps balances the counteracting mesoscale phase separation during heating with nanoscale duplex recognition during cooling to yield a diversity of complex all-DNA colloids with control over the internal dynamics and of their superstructures. Our approach provides a facile and versatile platform to add mesostructural layers into hierarchical all-DNA materials. The high density of addressable ssDNA blocks opens routes for applications such as gene delivery, artificial evolution or spatially encoded (bio)materials.

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Publication: Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo

Abstract: The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineered ArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with the de novo formation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials.

Publication: Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo - Read More…

Publication: Photochemical Ligation Meets Nanocellulose: A Versatile Platform for Self-Reporting Functional Materials

Abstract: The sustainable origin and highly promising mechanical and functional properties of cellulose nanofibrils (CNFs) attract significant interest for the construction of advanced functional materials. One key aspects to promote functionality of CNF-based materials is to implement sophisticated, facile and versatile chemical functionalization principles for application-targeted modification of CNF properties, independent on whether aiming for functional surfaces, hydrogels or bulk materials. We herein merge for the first time a self-reporting photo-induced modular ligation, the UV-induced nitrile imine-mediated tetrazole/ene cycloaddition, with CNFs to control chemical functionality in space and time with the possibility for a macroscopic fluorescence readout of the reaction progress. We discuss this hetero-complimentary photo-conjugation with respect to immobilization of the photoactive tetrazole units on CNFs in bulk and dispersion, and demonstrate the application for the three important CNF-based material classes (surfaces, hydrogels and bioinspired nanocomposites) by modification with photo-complementary maleimide-tethered functional moieties. In addition to realizing selective biorecognition patterns on transparent nanopapers, we showcase photo-induced hydrogelation relevant for biomaterials, as well as mechanical stiffening in bioinspired nanocomposites in bulk. The photochemical ligation proceeds smoothly in all three materials of vastly different dynamics (solution to bulk) and hence establishes a platform methodology to promote self-reporting functionalization of diverse CNF-based materials.

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Publication: Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Abstract: Nanomedicines can be taken up by cells via nonspecific and dynamin‐dependent (energy‐dependent) clathrin and caveolae‐mediated endocytosis. While significant effort has focused on targeting pathway‐specific transporters, the role of nanobiophysics in the cell lipid bilayer nanoparticle uptake pathway remains largely unexplored. In this study, it is demonstrated that stiffness of lipid bilayer is a key determinant of uptake of liposomes by mammalian cells. Dynamin‐mediated endocytosis (DME) of liposomes is found to correlate with its phase behavior, with transition toward solid phase promoting DME, and transition toward fluidic phase resulting in dynamin‐independent endocytosis. Since liposomes can transfer lipids to cell membrane, it is sought to engineer the biophysical properties of the membrane of breast epithelial tumor cells (MD‐MBA‐231) by treatment with phosphatidylcholine liposomes, and elucidate its effect on the uptake of polymeric nanoparticles. Analysis of the giant plasma membrane vesicles derived from treated cells using flicker spectroscopy reveals that liposome treatment alters membrane stiffness and DME of nanoparticles. Since liposomes have a history of use in drug delivery, localized priming of tumors with liposomes may present a hitherto unexploited means of targeting tumors based on biophysical interactions

Publication: Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness - Read More…