Reversible Loading of Nanoscale Elements on a Multicomponent Supramolecular Polymer System by Using DNA Strand Displacement

Supramolecular & Biomaterials Chemistr

Photopatternable, Branched Polymer Hydrogels Based on Linear Macromonomers for 3D Cell Culture Applications

Photochemical ligation strategies in hydrogel materials are crucial to model spatiotemporal phenomena that occur in the natural extracellular matrix. We here describe the use of cyclic 1,2-dithiolanes to cross-link with norbornene on linear poly(ethylene glycol) polymers through UV irradiation in a rapid and byproduct-free manner, resulting in branched macromolecular architectures and hydrogel materials from low-viscosity precursor solutions. Oscillatory rheology and NMR data indicate the one-pot formation of thioether and disulfide cross-links. Spatial and temporal control of the hydrogel mechanical properties and functionality was demonstrated by oscillatory rheology and confocal microscopy. A cytocompatible response of NIH 3T3 fibroblasts was observed within these materials, providing a foothold for further exploration of this photoactive cross-linking moiety in the biomedical field.Supramolecular & Biomaterials Chemistr

Mesoscale characterization of supramolecular transient networks using SAXS and Rheology

Abstract: Hydrogels and, in particular, supramolecular hydrogels show promising properties for application in regenerative medicine because of their ability to adapt to the natural environment these materials are brought into. However, only few studies focus on the structure-property relationships in supramolecular hydrogels. Here, we study in detail both the structure and the mechanical properties of such a network, composed of poly(ethylene glycol), end-functionalized with ureido-pyrimidinone fourfold hydrogen bonding units. This network is responsive to triggers such as concentration, temperature and pH. To obtain more insight into the sol-gel transition of the system, both rheology and small-angle X-ray scattering (SAXS) are used. We show that the sol-gel transitions based on these three triggers, as measured by rheology, coincide with the appearance of a structural feature in SAXS. We attribute this feature to the presence of hydrophobic domains where cross-links are formed. These results provide more insight into the mechanism of network formation in these materials, which can be exploited for tailoring their behavior for biomedical applications, where one of the triggers discussed might be used

Switching the mode of drug release from a reaction-coupled low-molecular-weight gelator system by altering its reaction pathway

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an L-histidine methyl ester catalyst to prepare the drugloaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.Supramolecular & Biomaterials Chemistr

Grafting from a hybrid DNA-covalent polymer by hybridization chain reaction

Biological and Soft Matter Physic

Dielectric‐modulated biosensing with ultrahigh‐frequency‐operated graphene field‐effect transistors

Supramolecular & Biomaterials Chemistr

A Fast pH-Switchable and Self-Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

Supramolecular & Biomaterials Chemistr

Spatial and temporal modulation of cell instructive cues in a filamentous supramolecular biomaterial

Supramolecular materials provide unique opportunities to mimic both the structure and mechanics of the biopolymer networks that compose the extracellular matrix. However, strategies to modify their filamentous structures in space and time in 3D cell culture to study cell behavior as encountered in development and disease are lacking. We herein disclose a multicomponent squaramide-based supramolecular material whose mechanics and bioactivity can be controlled by light through co-assembly of a 1,2-dithiolane (DT) monomer that forms disulfide cross-links. Remarkably, increases in storage modulus from ∼200 Pa to >10 kPa after stepwise photo-cross-linking can be realized without an initiator while retaining colorlessness and clarity. Moreover, viscoelasticity and plasticity of the supramolecular networks decrease upon photo-irradiation, reducing cellular protrusion formation and motility when performed at the onset of cell culture. When applied during 3D cell culture, force-mediated manipulation is impeded and cells move primarily along earlier formed channels in the materials. Additionally, we show photopatterning of peptide cues in 3D using either a photomask or direct laser writing. We demonstrate that these squaramide-based filamentous materials can be applied to the development of synthetic and biomimetic 3D in vitro cell and disease models, where their secondary cross-linking enables mechanical heterogeneity and shaping at multiple length scales.Toxicolog

Structure to Function in Supramolecular Polymers and Materials

Supramolecular & Biomaterials Chemistr