2. Academic Validation
  3. Enzymatically Bioactive Nucleus Pulposus Matrix Hydrogel Microspheres for Exogenous Stem Cells Therapy and Endogenous Repair Strategy to Achieve Disc Regeneration

Enzymatically Bioactive Nucleus Pulposus Matrix Hydrogel Microspheres for Exogenous Stem Cells Therapy and Endogenous Repair Strategy to Achieve Disc Regeneration

  • Adv Sci (Weinh). 2023 Dec 25:e2304761. doi: 10.1002/advs.202304761.
Yizhong Peng 1,  Xuanzuo Chen 1,  Qimin Zhang 2,  Sheng Liu 1,  Wei Wu 1,  Kanglu Li 1,  Hui Lin 1,  Xiangcheng Qing 1,  Yan Xiao 3,  BaiChuan Wang 1,  Daping Quan 4,  Shiqing Feng 5 6 7,  Zilong Rao 4,  Ying Bai 4,  Zengwu Shao 1
Affiliations

Affiliations

  • 1 Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Department of Radiology, Wuhan Third Hospital, Tongren Hospital of Wuhan University, 241 Pengliuyang Road, Wuhan, Hubei, 430063, China.
  • 3 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4 School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510127, China.
  • 5 The Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250033, P. R. China.
  • 6 Department of Orthopaedics Tianjin Medical University General Hospital, Tianjin Medica University, International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, 300052, P. R. China.
  • 7 Department of Orthopaedics Qilu Hospital of Shandong University, Shandong University Centre for Orthopaedics, Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, P. R. China.
PMID: 38145353 DOI: 10.1002/advs.202304761
Abstract

Exogenous stem cell therapy and endogenous repair has shown great potential in intervertebral disc regeneration. However, limited nutrients and accumulation of lactate largely impair the survival and regenerative capacity of implanted stem cells and endogenous nucleus pulposus cells (NPCs). Herein, an injectable hydrogel microsphere (LMGDNPs) have been developed by immersing lactate oxidase (LOX)-manganese dioxide (MnO2 ) nanozyme (LM) into glucose-enriched decellularized nucleus pulposus hydrogel microspheres (GDNPs) through a microfluidic system. LMGDNPs showed a delayed release profile of LOX and satisfactory enzymatic capacity in consuming lactate. Mesenchymal stem cells (MSCs) plated on LMGDNPs exhibited better cell viability than cells on GelMA and decellularized nucleus pulposus microspheres (DNP) and showed a obviously increased NPCs phenotype. LMGDNPs prevented MSCs and NPCs death and promoted extracellular matrix synthesis by exhausting lactate. It is determined that LMGDNPs promoted NPCs Autophagy by activating transforming growth factor β2 overlapping transcript 1 (TGFB2-OT1), relying on the nanozyme. MSCs-loaded LMGDNPs largely preserved disc hydration and alleviated matrix degradation in vivo. Summarily, LMGDNPs promoted cell survival and matrix regeneration by providing a nutrient supply, exhausting lactate, and activating Autophagy via TGFB2-OT1 and its downstream pathway and may serve as an ideal delivery system for exogenous stem cell therapy and endogenous repair.

Keywords

TGFB2-OT1; autophagy; intervertebral disc degeneration; lactate; microfluidic system; nanozyme.

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