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

doi:10.1016/j.bioactmat.2022.07.024

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. eCollection 2023 Mar.

Authors

Kai-Shun Xia^{1

2

3

4}, Dong-Dong Li⁵, Cheng-Gui Wang⁶, Li-Wei Ying⁷, 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 Slater⁸, Jian-Bin Tang⁵, 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.

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.