Surface‐Bound Gene‐Functionalized Injectable Short Fibers via Reversing Collagen Aging for Inhibiting Intervertebral Disc Degeneration

Abstract Collagen aging, which results from senescent nucleus pulposus (NP) cells, is a key factor in intervertebral disc degeneration (IDD). Traditional therapies that target the removal of senescent cells fail to address the underlying problem of collagen aging. Therefore, surface‐bound gene‐functionalized injectable short fibers are developed to inhibit collagen aging using a combination of plasma discharge modification and oxidative‐responsive liposomes. Initially, oxidative‐responsive liposomes are prepared by integrating p16‐siRNA with an oxidation‐sensitive phospholipid. Surface‐bound gene‐functionalized injectable short fibers (p16‐LP@SF) are then developed by grafting liposomes onto plasma‐activated carboxylated short fibers. In vitro experiments demonstrate that p16‐LP@SF triggers the release of p16‐LP from carboxylated short fibers through “broken bond” detachment in response to excessive reactive oxygen species (ROS) in the IDD microenvironment, and effectively inhibited senescence in NP cells. In vivo studies reveal that p16‐LP@SF promotes the production of collagen type II (COL‐II) and rebuilt the extracellular matrix (ECM). RNA‐sequencing analysis reveals that p16‐LP@SF significantly increases collagen deposition and inhibits collagen aging by activating the TGF‐β and BMP signaling pathways. In this study, short fibers designed to remodel the ECM of the NP are developed for the first time, which provides a novel therapeutic strategy for IDD by reversing collagen aging.