Poster Presentation 50th International Society for the Study of the Lumbar Spine Annual Meeting 2024

 Extracellular vesicles derived from myofibroblasts leverages a bio-integrated polymer gel for annulus fibrosus repair (#186)

Yifan Shen 1 , Libin Pang 2 , Chao Jiang 1 , Jiale Jin 2 , Yijian Zhang 3 , Hongyuan Xing 1 , Jiafeng Li 4 , Honghao Wu 1 , Jingyao Chen 5 , Ming Guan 1 , Tonghe Zhu 6 , Zhongyang Gao 1 , Wenguo Cui 2 , Yue Wang 1
  1. Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  2. Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai, China
  3. The First Affiliated Hospital of Soochow University, Suzhou, China
  4. Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  5. Zhejiang University School of Medicine, Hangzhou
  6. Shanghai University of Engineering Science, Shanghai

INTRODUCTION:

Discectomy, perhaps the most common spine procedure, is effective in treating symptomatic lumbar disc herniation (LDH). This procedure, however, leaves the annulus fibrosus (AF) defect unrepaired. AF defect may lead to continuous leaking of immune-privileged NP components, which may ignite persistent inflammation and result in various clinical problems such as residual back pain, leg pain, and recurrent LDH. Although the harms of AF defect have been recognized for decades, repairing the AF defect remains to be a clinical challenge to date.

 

METHODS:

To address these issues, we developed a two-arm repair system: a "bio-brick" layer composed of modified PGS to maintain mechanical microenvironment of the disc; and a “bio-cement” smart hydrogel layer consisting of oxidized hyaluronic acid (HA) and microfluidic methacrylate gelatin (GelMA) microspheres for the delivery and sustained release of myofibroblast-derived extracellular vesicles (M-EVs). Cell proliferation assays, immunofluorescence staining, flow cytometry analysis, and proteomics were employed to explore the anti-inflammatory and proliferative effects of M-EVs and its underlying mechanisms. Rheological tests, porcine skin tests, limit compression tests, and cyclic compression tests were conducted on isolated porcine discs to evaluate the mechanical properties and viscosity of PGBgel. Additionally, radiological and histological studies were assessed in a rat model of AF defect, which was established by puncturing the caudal discs, to verify the effect of M-EVs@PGBgel.

 

RESULTS:

Our study demonstrated that M-EVs promote AF cells proliferation by activating ITGA6/PI3K/AKT pathway and inducing M2 macrophages polarization. The developed PGBgel is biocompatible, efficient in sustained release of M-EVs, and possesses excellent sealing function and maintain disc biomechanics. Using radiological, histological, and biomechanical studies, we demonstrated that the developed M-EVs@PGBgel could efficiently antagonize local inflammation, promote AF cell proliferation, and maintain the biomechanics of AF in rat and porcine discs which underwent discectomy.

 

DISCUSSION:

The M-EVs@PGBgel system provides a potential solution to the clinical challenge of repairing AF defects after discectomy. The bio-integrated system effectively promotes AF regeneration and addresses the mechanical and biological issues associated with AF deficiency. Further studies are warranted to explore the full potential of this approach and optimize its application in clinical settings.