2. Academic Validation
  3. Brachyury-Activated Fucoidan Hydrogel Microspheres Rejuvenate Degenerative Intervertebral Discs Microenvironment

Brachyury-Activated Fucoidan Hydrogel Microspheres Rejuvenate Degenerative Intervertebral Discs Microenvironment

  • Adv Sci (Weinh). 2025 Jun 20:e04195. doi: 10.1002/advs.202504195.
Yuhao Gong 1 2,  Wenxiao Shi 1 2,  Xingzhu Liu 3,  Hang Yu 1 2,  Yinghui Wu 1 2,  Yanzhang Xia 1 2,  Caichun Yue 1 2,  Chongkai Yang 1 2,  Cong Shen 4,  Renjun Pei 3,  Tianwen Xin 1 2,  Hailong Pei 5,  Jun Shen 1 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215006, P. R. China.
  • 2 Suzhou Key Laboratory of Orthopedic Medical Engineering, the Affiliated Suzhou Hospital of Nanjing Medical University，Suzhou Municipal Hospital, Suzhou, 215006, P. R. China.
  • 3 CAS Key Laboratory of Nano-Bio Interface, Division of Nanobio-medicine, Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences, Suzhou, 215123, P. R. China.
  • 4 State Key Laboratory of Reproductive Medicine, Center for Reproduction and Genetics, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, 215002, P. R. China.
  • 5 State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, P. R. China.
PMID: 40539715 DOI: 10.1002/advs.202504195
Abstract

Extracellular matrix (ECM) metabolic disorders and the establishment of inflammatory microenvironment are the primary pathological alterations associated with intervertebral disc degeneration (IVDD). The inflammatory microenvironment promotes ECM degradation, further exacerbating the vicious cycle of nucleus pulposus (NP) degeneration. This study introduces the mRNA encoding a novel therapeutic transcription factor, Brachyury (Bry), into nucleus pulposus cells (NPCs) using an injectable microsphere system composed of biomimetic GelMA/Fucoidan (FU) dual-component hydrogel (GF) and surface chemically grafted lipid nanoparticles (LNP) (BLNP@GF). The study aims to alleviate inflammatory response in the NP while restoring the ECM secretion function of NPCs and enhancing the ability of NPCs to withstand inflammatory stress, thereby restoring physiological balance in the NP microenvironment. The GF microspheres demonstrate injectability and porosity, facilitating efficient LNP loading through chemical grafting. In the LPS-simulated inflammatory microenvironment, sustained release of FU significantly reduces inflammatory activity in NPCs. Successful transfection with Bry mRNA upregulate ECM synthesis in degenerated NPCs. In a rat tail puncture IVDD model, local application of BLNP@GF microspheres effectively improved ECM remodeling in NP tissue, thereby ameliorating puncture-induced IVDD. In conclusion, FU-functionalized GelMA hydrogel microspheres loaded with Bry mRNA provide a promising new strategy for reversing IVDD.

Keywords

LNP; brachyury; fucoidan; hydrogel microspheres; intervertebral disc degeneration.

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