Polyrotaxanes are supramolecular assemblies consisting of cyclic molecules (e.g., α-cyclodextrins) and linear polymer chains (e.g., poly[ethylene glycol]), in which cyclic molecules can move along the polymer chain. Here, we examined the effect of functional groups introduced into the α-cyclodextrins of polyrotaxane on cell responses such as adhesion, proliferation, and differentiation. Polyrotaxane-based triblock copolymers modified with methyl (CH₃, hydrophobic, and nonionic), hydroxy (OH, hydrophilic and nonionic), amino (NH₂, cationic), and sulfo (SO₃H, anionic) groups were coated on the surface of the culture plate to fabricate polyrotaxane surfaces with different surface chemistries. The chemical compositions of each surface were determined via time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy. The contact angle hysteresis reflecting the molecular mobility and zeta potential of each polyrotaxane surface changed depending on the functional groups. When osteoblast and adipocyte differentiation was induced in human mesenchymal stem cells cultured on each polyrotaxane surface, the cells adhered to the SO₃H-modified polyrotaxane surfaces exhibited osteoblast differentiation, whereas the cells adhered to the OH-, NH₂-, and SO₃H-modified polyrotaxane surfaces preferentially underwent adipocyte differentiation compared with those on the unmodified and CH₃-modified polyrotaxane surfaces. Interestingly, the SO₃H-modified polyrotaxane surfaces promoted both osteoblast and adipocyte differentiation. High molecular mobility and negative charge on the SO₃H-modified polyrotaxane surfaces are expected to contribute to the facilitation of both osteoblast and adipocyte differentiation.

A conjugate of an anti-HER2 antibody and polyrotaxane containing methylated β-cyclodextrins (Me-PRX) was designed to achieve a tumor-specific delivery of Me-PRX. The antibody–Me-PRX conjugates efficiently uptaken into HER2-positive cells and induced autophagic cell death.

Oral tissue regeneration has received growing attention for improving the quality of life of patients. Regeneration of oral tissues such as alveolar bone and widely defected bone has been extensively investigated, including regenerative treatment of oral tissues using therapeutic cells and growth factors. Additionally, small-molecule drugs that promote bone formation have been identified and tested as new regenerative treatment. However, treatments need to progress to realize successful regeneration of oral functions. In this review, we describe recent progress in development of regenerative treatment of oral tissues. In particular, we focus on cyclodextrin (CD)-based pharmaceutics and polyelectrolyte complexation of growth factors to enhance their solubility, stability, and bioactivity. CDs can encapsulate hydrophobic small-molecule drugs into their cavities, resulting in inclusion complexes. The inclusion complexation of osteoinductive small-molecule drugs improves solubility of the drugs in aqueous solutions and increases in vitro osteogenic differentiation efficiency. Additionally, various anionic polymers such as heparin and its mimetic polymers have been developed to improve stability and bioactivity of growth factors. These polymers protect growth factors from deactivation and degradation by complex formation through electrostatic interaction, leading to potentiation of bone formation ability. These approaches using an inclusion complex and polyelectrolyte complexes have great potential in the regeneration of oral tissues.

Biointerfaces based on polyrotaxane (PRX), consisting of α-cyclodextrins (α-CDs) threaded on a poly(ethylene glycol) (PEG) chain, are promising functionalized platforms for culturing cells. PRXs are characterized by the molecular mobility of constituent molecules where the threading α-CDs can move and rotate along the PEG chain. Taking advantage of this mobility, we have previously succeeded in demonstrating the regulation of cellular responses, such as cellular adhesion, proliferation, and differentiation. In the present study, we investigated differences in the cellular responses to PRX surfaces versus commercially available tissue culture polystyrene (TCPS) surfaces using fibroblasts, preosteoblasts, and preadipocytes. PRX surfaces were found to more significantly promote cellular proliferation than the TCPS surfaces, regardless of the cell type. To identify the signaling pathways involved in the activation of cellular proliferation, a DNA microarray analysis was performed. PRX surfaces showed a significant increase in the integrin-mediated cell adhesion and focal adhesion pathways. Furthermore, PRX surfaces also promoted osteoblast differentiation more than TCPS. These results suggest that structural features of PRX surfaces act as mechanical cues to dominate cellular proliferation and differentiation.