Stiff micelle-crosslinked hyaluronate hydrogels with low swelling for potential cartilage repair

Pluronic F127 diacrylate (F127DA) nano-micelle crosslinked methacrylated hyaluronic acid (MeHA) hydrogels (NMgels) with strong compressive properties have been demonstrated in our previous study. The current study further focuses on how the F127DA micelles and long-term swelling affect the mechanical performance of hydrogels from the view of in vitro/in vivo applications. Co-contributions of the F127DA micelles and MeHA to the compression performance are first investigated through mechanical analysis and cyclic loading/unloading tests before and after swelling. The optimized NMgel with F127DA micelles of 15 wt% and MeHA of 1.5 wt% (F15H1.5) exhibits a low swelling ratio and a well-maintained network in pH = 7.4 phosphate buffered saline. The abundant hydration significantly affects the initial mechanical properties of the hydrogels. After swelling, the compressive strength, modulus and fracture energy of F15H1.5 NMgel decrease from ∼3.44 MPa, ∼312 kPa and ∼407.5 kJ m-3 to 0.59 MPa, ∼55 kPa, and ∼81.8 kJ m-3, respectively. The energy dissipation of the first loading-unloading cycle dramatically decreases from ∼21.5 kJ m-3 to ∼6.0 kJ m-3 as well. Nevertheless, the gel still retains excellent stiffness, toughness and self-recovery due to the dense and strong micelle linkages. In vivo studies show that the implantation of F15H1.5 hydrogel in thyroid cartilage defects of rabbit larynx effectively promotes the regeneration of cartilage after 8 weeks. These results indicate that the stiff NMgel is a promising cartilage tissue engineering scaffold for the regeneration of cartilage in vivo.