An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration

  • Bioact Mater. 2022 Aug 14:21:69-85. doi: 10.1016/j.bioactmat.2022.07.024.
Kai-Shun Xia  1  2  3  4 ,  Dong-Dong Li  5 ,  Cheng-Gui Wang  6 ,  Li-Wei Ying  7 ,  Jing-Kai Wang  1  2  3  4 ,  Biao Yang  1  2  3  4 ,  Jia-Wei Shu  1  2  3  4 ,  Xian-Peng Huang  1  2  3  4 ,  Yu-Ang Zhang  1  2  3  4 ,  Chao Yu  1  2  3  4 ,  Xiao-Peng Zhou  1  2  3  4 ,  Fang-Cai Li  1  2  3  4 ,  Nigel K H Slater  8 ,  Jian-Bin Tang  5 ,  Qi-Xin Chen  1  2  3  4 ,  Cheng-Zhen Liang  1  2  3  4
Affiliations
  • 1. Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China.
  • 2. Orthopedics Research Institute of Zhejiang University, Zhejiang University, Hangzhou, 310009, Zhejiang, PR China.
  • 3. Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China.
  • 4. Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, Zhejiang Province, PR China.
  • 5. 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.
  • 6. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, PR China.
  • 7. Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, 317099, Zhejiang, PR China.
  • 8. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
PMID: 36017070 DOI: 10.1016/j.bioactmat.2022.07.024
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.

Keywords
Biomaterial pre-modification; Esterase-responsive nano micell; Intervertebral disc degeneration; Nucleus pulposus progenitor cells; Synergistic transplantation therapy.
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