Robustly Injectable Tetra-PEG Hydrogel Sealants for Annulus Fibrosus Repair

Discectomy serves as the primary therapeutic approach for lumbar disc herniation, but the annular fibrosus defects after discectomy may lead to recurrence of disc herniation. Despite recent advances in bioinspired adhesives to seal the AF defect, the growing popularity of endoscopic discectomy has put forward high requirements for the tissue bioadhesives with rapid injectability, easy operation, and robust tissue adhesion in underwater environments. Herein, a rapidly in situ forming injectable tetra-PEG bioadhesive (ISG) comprising of FDA-approved tetra-armed poly (ethylene glycol) amine (tetra-PEG-NH₂) and tetra-armed poly (ethylene glycol) succinimidyl glutarate (tetra-PEG-SG) for the sutureless closure of AF defects, is reported. Relying on quick ammonolysis reaction between N-hydroxysuccinimide (NHS)-ester of tetra-PEG-SG polymer and amine groups of tetra-PEG-NH₂ polymer and tissue proteins, the uniform networks are formed within seconds with easy injection, efficient waterproofness, instant tissue adhesion, and durable compliance. The goat lumbar discectomy model was used to assess the effect of ISG hydrogels in vivo. The results reveal that the resultant ISG bioadhesive can effectively maintain the disc height, fuse with the host tissue, ameliorate IVD degeneration, and retain the initial biomechanics. Together, this study provides an efficient strategy of in situ injectable glue for the minimally invasive treatment of AF defects.