Bioactive Materials (Mar 2023)
An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration
- Kai-shun Xia,
- Dong-dong Li,
- Cheng-gui Wang,
- Li-wei Ying,
- Jing-kai Wang,
- Biao Yang,
- Jia-wei Shu,
- Xian-peng Huang,
- Yu-ang Zhang,
- Chao Yu,
- Xiao-peng Zhou,
- Fang-cai Li,
- Nigel K.H. Slater,
- Jian-bin Tang,
- Qi-xin Chen,
- Cheng-zhen Liang
Affiliations
- Kai-shun Xia
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Dong-dong Li
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering, Collage of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, PR China
- Cheng-gui Wang
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, PR China
- Li-wei Ying
- Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, 317099, Zhejiang, PR China
- Jing-kai Wang
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Biao Yang
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Jia-wei Shu
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Xian-peng Huang
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Yu-ang Zhang
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Chao Yu
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Xiao-peng Zhou
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Fang-cai Li
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China
- Nigel K.H. Slater
- Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom
- Jian-bin Tang
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering, Collage of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, PR China; Corresponding author. Key Laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineering, Collage of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, PR China.
- Qi-xin Chen
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Corresponding author. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China.
- Cheng-zhen Liang
- Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China; Corresponding author. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China.
- Journal volume & issue
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Vol. 21
pp. 69 – 85
Abstract
Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro; their further synergistic transplantation yielded effective functional recovery, histological regeneration, and inhibition of pyroptosis during IDD regeneration. Herein, we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.