Affiliation:
1. Shanghai Tongji Hospital School of Life Science and Technologies Tongji University Shanghai 200065 China
2. Department of Chemistry and Chemical Biology Rutgers The State University of New Jersey Piscataway NJ 08854 USA
3. Department of Neurosurgery CHA University School of Medicine CHA Bundang Medical Center, 59 Yaptap‐ro, Bundang‐gu, Seongnam‐si Gyeonggi‐do 13496 Republic of Korea
Abstract
AbstractDegeneration of fibrocartilaginous tissues is often associated with complex pro‐inflammatory factors. These include reactive oxygen species (ROS), cell‐free nucleic acids (cf‐NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all‐in‐one nanoscaffold‐based 3D porous hybrid protein (3D‐PHP) self‐therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D‐PHP nanoscaffold is synthesized by introducing a novel nanomaterial‐templated protein assembly (NTPA) strategy. 3D‐PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli‐responsive drug release, disc‐mimetic stiffness, and excellent biodegradability. Enzyme‐like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf‐NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D‐PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long‐term pain reduction. Therefore, self‐therapeutic and epigenetic modulator‐encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.
Funder
National Science Foundation
National Institutes of Health
National Heart, Lung, and Blood Institute
Catholic University of Korea
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
1 articles.
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