An Injectable Hydrogel Foam Enables Mechanical Resilience and Zero-Order Release of Growth Factors for Intervertebral Disc Repair

Intervertebral disc degeneration (IVDD) is a global challenge to cure effectively. Although current hydrogel-based therapies are promising, they often have difficulty of completely reversing IVDD progression. Herein, we report an injectable and growth factor-laden hydrogel foam (IHFs@GFs) for the treatment of IVDD. IHF is prepared from methylphenyltetrazine-modified hyaluronic acid (HA-MTZ), norbornene-modified gelatin (Gelatin-NB), and norbornene-modified cellulose nanofibers (CNF-NB). MTZ reacts with NB to release N2, spontaneously generating numerous closed and spherical N2 bubbles in hydrogels. These N2 bubbles endow IHF with good mechanical resilience and pressure buffering. Moreover, IHF shows zero-order release of transforming growth factor-β3 and insulin-like growth factor-1. Notably, after 8 weeks of treatment with IHFs@GFs, the disc height and hydration in degenerated IVD are significantly restored to over 90%, thereby enabling effective treatment of IVDD. The IHF integrates biomechanics and zero-order release of biologics within a single system, offering a promising platform for IVDD treatment.