Fucoidan-functionalized gelatin methacryloyl microspheres ameliorate intervertebral disc degeneration by restoring redox and matrix homeostasis of nucleus pulposus

Yangfeng Li; Xin Tian; Wei He; Chenyang Jin; Chunju Yang; Zejun Pan; Yong Xu; Huilin Yang; Hao Liu; Tao Liu; Fan He

doi:10.1016/j.ijbiomac.2023.126166

Fucoidan-functionalized gelatin methacryloyl microspheres ameliorate intervertebral disc degeneration by restoring redox and matrix homeostasis of nucleus pulposus

Int J Biol Macromol. 2023 Oct 1:250:126166. doi: 10.1016/j.ijbiomac.2023.126166. Epub 2023 Aug 6.

Authors

Yangfeng Li¹, Xin Tian¹, Wei He¹, Chenyang Jin², Chunju Yang², Zejun Pan¹, Yong Xu¹, Huilin Yang¹, Hao Liu³, Tao Liu⁴, Fan He⁵

Affiliations

¹ Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Orthopaedic Institute, Suzhou Medical College, Soochow University, Suzhou 215000, China.
² Orthopaedic Institute, Suzhou Medical College, Soochow University, Suzhou 215000, China; Suzhou Medical College of Soochow University, Suzhou 215123, China.
³ Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Orthopaedic Institute, Suzhou Medical College, Soochow University, Suzhou 215000, China. Electronic address: 0930705006@suda.edu.cn.
⁴ Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China. Electronic address: liutao8250@suda.edu.cn.
⁵ Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Orthopaedic Institute, Suzhou Medical College, Soochow University, Suzhou 215000, China. Electronic address: fanhe@suda.edu.cn.

PMID: 37553034
DOI: 10.1016/j.ijbiomac.2023.126166

Abstract

Loss of extracellular matrix (ECM) and dehydration of the nucleus pulposus (NP) are major pathological characteristics of intervertebral disc degeneration (IVDD), the leading cause of low back pain. Excessive reactive oxygen species (ROS) induced by proinflammatory cytokines substantially contribute to IVDD pathogenesis. This study aimed to examine the potential of fucoidan in protecting the matrix metabolism of NP cells and its therapeutic efficacy in the prevention of IVDD. In an inflammatory environment induced by interleukin (IL)-1β, fucoidan treatments demonstrated a dose-dependent enhancement of ECM production in NP cells, while concurrently reducing the expression of matrix degradation enzymes. The protective effect of fucoidan was mediated through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and subsequent induction of antioxidant enzymes, whereas silencing Nrf2 abrogated the protection of fucoidan on NP cells against IL-1β-induced oxidative stress. Moreover, a novel fucoidan-functionalized gelatin methacryloyl microsphere (Fu@GelMA-MS) was synthesized. The in vivo application of Fu@GelMA-MS via in situ injection in a rat caudal IVD model effectively conserved the ECM components and maintained the hydration of the NP tissue, thereby preventing IVDD caused by puncture. Collectively, fucoidan-functionalized hydrogel microspheres represent a promising strategy for the regeneration of NP and the treatment of IVDD.

Keywords: Fucoidan; Intervertebral disc degeneration; Microspheres; NRF2; Nucleus pulposus; Reactive oxygen species.