Due to their low cytotoxicity, controllable size, and unique architecture, cyclodextrin (CD)-based polyrotaxanes and polypseudorotaxanes have inspired interesting exploitation as novel biomaterials. This review will update the recent progress in the studies on the structures of polyrotaxanes and polypseudorotaxanes based on different CDs and polymers, followed by summarizing their potential applications in life science and biotechnology, such as drug delivery, gene delivery, and tissue engineering. CD-based biodegradable polypseudorotaxane hydrogels could be used as promising injectable drug delivery systems for sustained and controlled drug release. Polyrotaxanes with drug or ligand-conjugated CDs threaded on polymer chain with biodegradable end group could be useful for controlled and multivalent targeting delivery. Cationic polyrotaxanes consisting of multiple oligoethylenimine-grafted CDs threaded on a block copolymer chain were attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene transfection efficiency. Cytocleavable end caps were also introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. Finally, hydrolyzable polyrotaxane hydrogels with cross-linked α-CDs could be a desirable scaffold for cartilage and bone tissue engineering.

Supramolecular polymers based on cyclodextrins (CDs) have inspired interesting and rapid developments as novel biomaterials in a broad range of drug and gene delivery applications, due to their low cytotoxicity, controllable size, and unique architecture. This review will summarize the potential applications of polyrotaxanes in the field of drug delivery and gene delivery. Generally, cyclodextrin-based biodegradable polypseudorotaxane hydrogels could be used as a promising injectable drug delivery system for sustained and controlled drug release. Temperature-responsive, pH-sensitive, and controllable hydrolyzable polyrotaxane hydrogels have attracted much attention because of their controllable properties, and the self-assembly micelles formed by amphiphilic copolymer threaded with CDs could be used as a carrier for controlled and sustained drug release. Polyrotaxanes with drug or ligand conjugated CDs threaded on a polymer chain with a biodegradable end group could be useful for controlled and multivalent targeted delivery. In the field of gene delivery, cationic polyrotaxanes consisting of multiple OEI-grafted CDs threaded on a block copolymer chain are attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene delivery capability. Furthermore, cytocleavable end-caps were introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. The development of the supramolecular approach using CD-containing polyrotaxanes is expected to provide a new paradigm for biomaterials.