Engineered microalgae-driven gel platform promotes the repairing of senescence-associated intervertebral disc degeneration in rats and goats.

Intervertebral disc degeneration (IDD), a major cause of low back pain, is closely linked to oxidative stress-mediated inflammation and nucleus pulposus cell (NPC) senescence; however, current clinical treatments fail to effectively target these underlying mechanisms. This study presents a multifunctional therapeutic platform that integrates engineered microalgae with a nucleus pulposus (NP)-like hydrogel to fill disc defects and mitigate senescence-associated IDD. Engineered microalgae, which exhibit nanozyme-like activity, demonstrate potent antioxidant effects through reactive oxygen species (ROS) scavenging. Meanwhile, the NP-like hydrogel activates platelets to release growth factors that counteract cellular senescence. In vitro, the engineered microalgae effectively scavenge intracellular ROS, stabilize mitochondrial membrane potential, reduce inflammatory cytokine secretion, and consequently alleviate NPC senescence while restoring extracellular matrix (ECM) homeostasis. Transcriptomic analysis reveals that the engineered microalgae diminish oxidative stress-mediated acute inflammatory responses, reduce production of inflammatory cytokines (TNF-α), and downregulate senescence-associated secretory phenotype factors (IL-6). In vivo, local injection of the engineered microalgae delays needle puncture-induced IDD in rats. Furthermore, given the limited clinical translatability of rodent models, a goat NP defect model is established. Implantation of the engineered microalgae-hydrogel platform effectively fills disc defects and promotes disc repair in goats. This platform represents a promising therapeutic strategy with strong translational potential for preventing and treating IDD.