Supramolecular Surface Coatings with Acetylated Polyrotaxane-Based Triblock Copolymers for Thermal Regulation of Cell Adhesion and Fabrication of Cell Sheets.

Polyrotaxanes (PRXs) containing acetylated α-cyclodextrins exhibit a temperature-dependent phase transition in aqueous solutions across their lower critical solution temperature (LCST) of approximately 26.6 °C. To gain insights into the interactions of acetylated PRXs (Ac-PRXs) with biological components, thermoresponsive supramolecular surfaces were prepared by coating tissue culture polystyrene (TCPS) surfaces with Ac-PRX triblock copolymers, and their surface properties across the LCST were evaluated.

Cografting of Zwitterionic Sulfobetaines and Cationic Amines on β-Cyclodextrin-Threaded Polyrotaxanes Facilitates Cellular Association and Tissue Accumulation with High Biocompatibility.

β-Cyclodextrins (β-CDs) and β-CD-containing polymers have attracted considerable attention as potential candidates for the treatment of cholesterol-related metabolic and intractable diseases. We have advocated the use of β-CD-threaded acid-degradable polyrotaxanes (PRXs) as intracellular delivery carriers for β-CDs. As unmodified PRXs are insoluble in aqueous solutions, chemical modification of PRXs is an essential process to improve their solubility and impart novel functionalities.

Acetylation of Cyclodextrin-Threaded Polyrotaxanes Yields Temperature-Responsive Phase Transition and Coacervate Formation Properties.

Stimuli-responsive materials have received considerable attention for their application in biomedical fields. Herein, the temperature-dependent phase transition behavior of acetylated polyrotaxanes (Ac-PRXs) consisting of acetylated cyclodextrins threaded onto a linear axle polymer in aqueous solution is investigated. The aqueous solutions of Ac-PRXs exhibit temperature-dependent transmittance changes when the degree of acetylation is 30-40%.

Cellular Orientation on Repeatedly Stretching Gelatin Hydrogels with Supramolecular Cross-Linkers.

The cytocompatibility of biological and synthetic materials is an important issue for biomaterials. Gelatin hydrogels are used as biomaterials because of their biodegradability. We have previously reported that the mechanical properties of gelatin hydrogels are improved by cross-linking with polyrotaxanes, a supramolecular compound composed of many cyclic molecules threaded with a linear polymer.

Polyelectrolyte Complexes between Polycarboxylates and BMP-2 for Enhancing Osteogenic Differentiation: Effect of Chemical Structure of Polycarboxylates.

Bone morphogenetic protein 2 (BMP-2) has received considerable attention because of its osteoinductivity, but its use is limited owing to its instability and adverse effects. To reduce the dose of BMP-2, complexation with heparin is a promising approach, because heparin enhances the osteoinductivity of BMP-2. However, the clinical use of heparin is restricted because of its anticoagulant activity.

Emerging Nanoassembly of Polyrotaxanes Comprising Acetylated α-Cyclodextrins and High-Molecular-Weight Axle Polymer.

Acetylated α-cyclodextrin (α-CD)/poly(ethylene glycol) (PEG)-based polyrotaxanes (Ac-PRXs) with varying degrees of acetylation (DA) and molecular weight of axle PEG were synthesized and their solubility in aqueous solutions was investigated. Ac-PRXs with low DA (less than 35%) were dissolved in aqueous solutions without considering the molecular weight of axle PEG, whereas Ac-PRXs with high DA (more than 40%) and low molecular weight of axle PEG (less than 35000) were precipitated into the solutions. Interestingly, Ac-PRXs with high DA and high molecular weight of axle PEG (100000) exhibited a colloidal dispersion in aqueous solutions.

Scavenger Receptor A-Mediated Targeting of Carboxylated Polyrotaxanes to Macrophages and the Impacts of Supramolecular Structure.

Because macrophages are involved in the pathology of many diseases, targeting delivery of therapeutic molecules to macrophages is important issue. Polyrotaxanes (PRXs) composed of multiple cyclodextrins threaded with a linear polymer were utilized as a therapeutic agent for metabolic disease and for regulating cellular metabolism. For targeting delivery of PRXs to macrophages, carboxyethyl ether group-modified PRXs (CEE-PRXs) are designed for promoting interaction to macrophage scavenger receptor class A (SR-A).

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials.

Cyclodextrin (CD)-threaded polyrotaxanes (PRXs) with reactive functional groups at the terminals of the axle polymers are attractive candidates for the design of supramolecular materials. Herein, we describe a novel and simple synthetic method for end-reactive PRXs using bis(2-amino-3-phenylpropyl) poly(ethylene glycol) (PEG-Ph-NH) as an axle polymer and commercially available 4-substituted benzoic acids as capping reagents. The terminal 2-amino-3-phenylpropyl groups of PEG-Ph-NH block the dethreading of the α-CDs after capping with 4-substituted benzoic acids.

Potentiating bioactivity of BMP-2 by polyelectrolyte complexation with sulfonated polyrotaxanes to induce rapid bone regeneration in a mouse calvarial defect.

Bone reconstruction is a challenging issue in the regeneration of surgically removed bone and disease-related bone defects. Although bone morphogenetic protein-2 (BMP-2) has received considerable attention as a bone regeneration inducer, a high dose of BMP-2 is typically required due to its short life-time under in vivo conditions. We have proposed a method to enhance the osteogenetic differentiation ability of BMP-2 in vitro that is based on supramolecular polyelectrolyte complexation with sulfonated polyrotaxanes (PRXs) consisting of sulfopropyl ether (SPE)-modified α-cyclodextrins threaded along a poly(ethylene glycol) chain capped with terminal bulky stopper molecules.

Supramolecular inclusion complexation of simvastatin with methylated β-cyclodextrins for promoting osteogenic differentiation.

Statins are recognized as a potential candidate to induce the regeneration of bone. However, statins are a strongly hydrophobic drug and it is difficult to administer at the local sites. In this study, the inclusion complexes of simvastatin (SV) with hydroxypropyl-β-cyclodextrin (HP-β-CD) and randomly methylated β-cyclodextrin (RM-β-CD) were prepared to improve the water-solubility and the osteogenic differentiation ability of the inclusion complexes in MC3T3-E1 cells was investigated.

A designed room-temperature triplet ligand from pyridine-2,6-diyl bis(tert-butyl nitroxide).

The magnetic study on newly developed 4-mesitylpyridine-2,6-diyl bis(tert-butyl nitroxide) shows that almost the whole population has a ground triplet state at room temperature, and the ability of complex formation as a tridentate triplet ligand was proven with a diamagnetic yttrium(iii) ion.