Cyclodextrin-Based Supramolecular Hydrogels in Tissue Engineering and Regenerative Medicine

Abstract

Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host-guest interactions. CDs form supramolecular host-guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication strategies for CD-based supramolecular hydrogels and their applications in tissue engineering and regenerative medicine, with focused analysis on wound healing, corneal regeneration, and bone repair. We critically analyze CD-guest molecular interaction mechanisms and innovative therapeutic implementations, highlighting the significant potential of CD hydrogels for tissue regeneration while addressing clinical translation challenges and future directions.

Keywords: cyclodextrins (CDs); hydrogels; supramolecular; tissue repair and regeneration.

Figure 1

(A) Schematic structures of rotaxane, catenane, polyrotaxane, and polycatenane, Copyright © 2025 Elsevier B.V. [27]; (B) The PXRD profiles of α-CD, NH2-PEG-NH2, and polyrotaxane formed by α-CD, NH2-PEG-NH2, Copyright © 2025 BioMed Central Ltd. unless otherwise stated; (C) XRD patterns of DEX, γ-CD, DEX-NE, and DEX-NPH at different γ-CD concentrations (25%, 30%, 35%), Copyright © 2025 Elsevier B.V.; (D) SEM images of a TDU-CD lattice, Copyright © 1999–2025 John Wiley and Sons, Inc or related companies; (E) Schematic representation of CS-mPEG preparation, (i) XRD spectra, (ii) SEM image, Copyright © 2025 Elsevier B.V.

Figure 4

(A) Schematic diagram of supramolecular hydrogel for cornea treatment [61], Copyright © 2025 Elsevier B.V.; (B) The DEX level in the tear fluid following topical instillation of different preparations at a dose of 4 μg DEX (n = 3), Copyright © 2025 Elsevier B.V.; (C) Confocal images of CEC encapsulated in s-HA, linear HA, and untreated groups, attached to the stroma layer of rabbit corneas in vitro after 4 days, Copyright © 2025 Elsevier B.V.; (D) c-MSCs encapsulated in s-HA and linear HA significantly increased the expression of growth factors, inflammatory and pro-inflammatory cytokines, and chemokines compared to c-MSCs in TCP (2D condition), Copyright © 2025 Elsevier B.V.

Scheme 1

CD-based hydrogels in tissue repair and regeneration.

Figure 2

(A) Schematic diagram of CD forming a host–guest complex with a guest molecule [4], Copyright © 2025 Elsevier B.V.; (B) Schematic illustration of the host–guest complex formed between Ad and β-CD, wherein the hydrophobic Ad moiety is encapsulated within the hydrophobic cavity of β-CD through supramolecular interactions, Copyright © 1999–2025 John Wiley and Sons, Inc or related companies; (C) Photoresponse processes of Azo-CD complexes, Copyright © 2025 Springer Nature Limited; (D) Oxidizes Fc to Fc⁺ to disassemble the host–guest complex, Copyright © 2023 Elsevier Inc.

Figure 3

(A) The ability of SMCT-6@Cur hydrogel to release Cur in vitro, Copyright © 2025 Elsevier B.V.; (B) Photograph of hydrogel-treated mouse wound 14 days later. Scale bar: 1 cm, Copyright © 2025 Elsevier B.V. (C) Schematic representation of the wound area of a mouse wound after 14 days of treatment with different samples, Copyright © 2025 Elsevier B.V.; (D) Photographs of wounds in mice of different days, Copyright © 2025 Elsevier B.V.; (E) Schematic representation of wound healing in mice of different days, Copyright © 2025 Elsevier B.V.

Figure 5

(A) Schematic diagram of supramolecular hydrogel for bone regeneration, modify from [70,71], Copyright © 2025 Elsevier B.V.; (B) Digital images showing hydrogel self-healing behavior as well as compression testing, Copyright © 2025 Elsevier B.V.; (C) Cyclic compression test curve of SF@HG@HA with 20% HA, Copyright © 2025 Elsevier B.V.; (D) Squeeze the hydrogel in PBS with a 28 G needle, Copyright © 2025 Elsevier B.V.; (E) 3D reconstruction images of knee joints, Copyright © 2025 Elsevier B.V.