Using cross-linked hyaluronic acid gel to prevent postoperative lumbar epidural space adhesion: in vitro and in vivo studies

  • Kun Wang
  • Xiao long Li
  • Jinbo Liu
  • Xiaoliang Sun
  • Huilin YangEmail author
  • Xin GaoEmail author
Original Article



Hyaluronic acid prevents tissue adhesion after different surgeries. Physical barriers and inflammatory regulation have been suggested to be involved in the mechanism of these clinical effects. However, the molecular mechanism by which hyaluronic acid prevents epidural adhesion has not yet been reported.


In the current in vivo studies, we investigated cross-linked hyaluronic acid gel in the regulation of scar gene expression, the accumulation of fibroblasts in scar tissue, and the prevention of epidural adhesion. The effect of cross-linked hyaluronic acid gel on the secretion of inflammatory factors was observed in vitro. In addition, to ensure the accuracy and reliability of the in vivo gene expression results, we used a cell model to detect the target genes in vitro.


The expression levels of TGFβ1 and COL1A1 mRNA were decreased in the cross-linked hyaluronic acid gel-treated group, and the protein expression of levels TGFβ1 and COL1A1 were also reduced, as detected by Western blotting in vitro and in vivo (P < 0.05). Histomorphometry results demonstrated that the number of fibroblasts in the experimental group was significantly lower than that in the control group 2 weeks postoperatively. Micro-CT scans showed that the cross-linked hyaluronic acid gel could reduce adhesion in the epidural space after laminectomy. Additionally, the cross-linked hyaluronic acid gel could inhibit IL-6 secretion.


These results indicate that cross-linked hyaluronic acid gel can prevent epidural adhesion by inhibiting inflammatory factors, such as IL-6, and downregulating TGFβ1 and COL1A1 mRNA expression.

Graphic abstract

These slides can be retrieved under Electronic Supplementary Material.


Laminectomy Epidural space adhesion Hyaluronic acid Fibrous tissue-regulated gene Inflammatory modulation 



The authors would like to thank Jizong Gao, MD, PhD, for his critical review and editorial help during the study and the drafting of the manuscript. We are also gratitude to an anonymous reviewer for his/her professional comments and suggestions during the reviewing processes.

Author contributions

Huilin Yang and Xin Gao conceived and designed the experiments. Kun Wang and Xiaolong Li performed the experiments. Xiaoliang Sun analyzed the data. Xiaolong Li contributed reagents/materials/analysis tools. Kun Wang wrote the paper. Jinbo Liu performed technical guidance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

586_2019_6193_MOESM1_ESM.pptx (1.5 mb)
Supplementary material 1 (PPTX 1570 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OrthopedicsThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of OrthopedicsThe People’s Hospital of Wujin Affiliated with Jiangsu UniversityChangzhouChina
  3. 3.Department of OrthopedicsThe Third Affiliated Hospital of Soochow UniversityChangzhouChina

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