Mechanically tough, adhesive, self-healing hydrogel promotes annulus fibrosus repair via autologous cell recruitment and microenvironment regulation

Annulus fibrosus (AF) defect is an important cause of disc re-herniation after discectomy. The selfregeneration ability of the AF is limited, and AF repair is always hindered by the inflammatory microenvironment after injury. Hydrogels represent one of the most promising materials for AF tissue engineering strategies. However, currently available commercial hydrogels cannot withstand the harsh mechanical load within intervertebral disc. In the present study, an innovative triple cross-linked oxidized hyaluronic acid (OHA)-dopamine (DA)- polyacrylamide (PAM) composite hydrogel, modified with collagen mimetic peptide (CMP) and supplied with transforming growth factor beta 1 (TGF- fi 1) (OHA-DA-PAM/CMP/TGFfi 1 hydrogel) was developed for AF regeneration. The hydrogel exhibited robust mechanical strength, strong bioadhesion, and significant self-healing capabilities. Modified with collagen mimetic peptide, the hydrogel exhibited extracellular-matrix-mimicking properties and sustained the AF cell phenotype. The sustained release of TGF- fi 1 from the hydrogel was pivotal in recruiting AF cells and promoting extracellular matrix production. Furthermore, the composite hydrogel attenuated LPS-induced inflammatory response and promote ECM synthesis in AF cells via suppressing NF kappa B/NLRP3 pathway. In vivo , the composite hydrogel successfully sealed AF defects and alleviated intervertebral disk degeneration in a rat tail AF defect model. Histological evaluation showed that the hydrogel integrated well with host tissue and facilitated AF repair. The strategy of recruiting endogenous cells and providing an extracellular-matrixmimicking and anti-inflammatory microenvironment using the mechanically tough composite OHA-DAPAM/CMP/TGF- fi 1 hydrogel may be applicable for AF defect repair in the clinic.