Supramolecular Injectable Hyaluronate Hydrogels for Cartilage Tissue Regeneration

Abstract

Mesenchymal stem cells (MSCs) have been widely investigated to repair injured cartilage tissues for the treatment of arthritis. Despite these great efforts, the difficulty in the spatiotemporal control of delivered cells has limited the further clinical development with rapid clearance. Here, we developed injectable hyaluronate (HA) hydrogels to encapsulate MSCs for controlled cartilage tissue regeneration based on the supramolecular chemistry between βcyclodextrin-modified HA (HA-CD) and adamantane (Ad)-modified HA (HA-Ad). Supramolecular HA hydrogels exhibited remarkable mechanical characteristics such as shear thinning and self-healing with a high cell viability of encapsulated MSCs. The spatiotemporally controlled delivery of MSCs from the supramolecular HA hydrogels resulted in the statistically significant chondrogenic differentiation and extracellular matrix deposition in vitro and in vivo. We could confirm the notable cartilage tissue regeneration in cartilage defect model rats after treatment with supramolecular HA hydrogels encapsulating MSCs for 28 days. Taken together, supramolecular HA hydrogels would be successfully harnessed as an injectable delivery system of MSCs for cartilage tissue regeneration and other tissue engineering applications.

Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

“…Jeong et al modified hyaluronic acid (HA)-based hydrogels by β-cyclodextrin. Resulted hydrogels demonstrated remarkable shear-thinning, cell viability, adhesive strength, and desirable mechanical properties for CTE applications [ 105 ]. Until now, several hydrogel substances have been employed for stem cell therapy.…”

“…In intrinsic self-healing hydrogels, the presence of hydrophobic interactions leads to the re-arrangement of hydrophobic blocks to reduce or eliminate contacts with water molecules. Jeon et al introduced novel hierarchical systems of non-covalent crosslinks with excellent stretchability and damage recovery created by incorporating amphiphilic polymers (UPyHCBA with an acrylic head, a hydrophobic alkyl spacer, and a 2-ureido-4-pyrimidone (UPy) tail) and surfactants (sodium dodecyl sulfate) into polyacrylamide hydrogels ( Figure 7 a) [ 105 ]. The obtained hydrogels were able to stretch ~100 times their initial length and to intrinsically self-heal within ~30 s. Using reversible hydrophobic interactions, Meng et al fabricated silk fibroin-based hydrophobic-association hydrogels incorporated into an alginate ionic network ( Figure 7 b) [ 184 ].…”

“…Recently, Jeong and co-workers reported injectable hydrogels based on β-cyclodextrin-modified hyaluronate and adamantane-modified HA, encapsulating mesenchymal stem cells (MSCs) for CTE applications. These hydrogels demonstrated remarkable mechanical characteristics including shear-thinning and self-healing with high cell viability [ 105 ]. The therapeutic efficacy of the HA hydrogels/MSCs for cartilage tissue regeneration was evaluated in vivo ( Figure 8 c), where the hydrogels/MSCs confirmed better macroscopic neocartilage formation covering the entire defect area compared with control groups.…”

“…Reproduced with permission from Ref. [ 105 ]. ( d ) The host-guest interactions between Azo derivatives and CD derivatives in the presence and absence of light and the schematic illustration of the alginate-based cyclodextrin/azo-polyacrylamide composite self-healing process.…”

Enhancing Stem Cell Therapy for Cartilage Repair in Osteoarthritis—A Hydrogel Focused Approach

“…Supramolecular networks are formed by reversible and non-covalent intermolecular interactions and allow to tailor the mechanic properties of hydrogel that recapitulate the dynamic and viscoelastic behaviors of ECM [ 44 ]. One of the most used mechanisms for synthesizing supramolecular biomaterials is through interactions between molecules of host and guest, which has been adopted to improve the regeneration of both hyaline cartilage and subchondral bone.…”