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

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

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.
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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