Implantable red blood cell gel loaded with IL-33 treats intervertebral disc degeneration through the PI3K/AKT signaling pathway

Background: Intervertebral disc degeneration remains a major therapeutic challenge, with biomedical interventions increasingly regarded as promising options. Methods: An implantable red blood cell–based gel incorporating interleukin-33 was developed to promote disc tissue repair. Results: Following implantation, the gel functioned as an efficient drug carrier while attracting a substantial population of macrophages, subsequently guiding their polarization through different phases to optimize the disc microenvironment. Conclusions: This strategy slowed the progression of disc degeneration by stimulating the proliferation of nucleus pulposus cells, suppressing apoptosis, and driving macrophage differentiation toward the M2 phenotype.