Poster Presentation 51st International Society for the Study of the Lumbar Spine Annual Meeting 2025

Characterized by a cascade of profound changes in nucleus pulposus (NP) cells, extracellular matrix (ECM), and biomechanics, intervertebral disc degeneration is a common multifactorial condition that may lead to various degenerative lumbar disorders. Therapeutic strategies targeting a single factor have shown limited efficacy in treating disc degeneration, and approaches that address multiple pathological ingredients are barely reported. In this study, we developed engineered cell membrane-encapsulated keratin nanoparticles to simultaneously alleviate NP cell senescence and promote ECM remodeling. To achieve this, we used salivary acid glycoengineered adipose mesenchymal stem cell membranes to coat keratin, a core protein for structural support and cellular protection. The synthesized cell membrane-coated keratin nanoparticles (MKNs) effectively protected mitochondrial integrity in NP cells from oxidative stress-induced damage. Moreover, MKNs modulated mitochondrial metabolism and attenuated NP cell senescence. In addition, MKNs activated integrins at cell membrane and enhanced the interactions between NP cells and ECM, resulting in increased ECM anabolism and decreased catabolism. The proposed multi-targeted strategy to block the degenerative cycle inside the disc is efficacious for treating disc degeneration and may have potential for clinical applicaiton.