Topically Applied Cross-Linked Hyaluronan Attenuates the Formation of Spinal Epidural Fibrosis in a Swine Model of Laminectomy

局部应用交联透明质酸可减弱猪椎板切除术模型中脊髓硬膜外纤维化的形成

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作者:Cheng-Li Lin, I-Ming Jou, Cheng-Yi Wu, Yuh-Ruey Kuo, Shih-Chieh Yang, Jung-Shun Lee, Yuan-Kun Tu, Sung-Ching Chen, Yi-Hung Huang

Abstract

Epidural fibrosis is an inevitable aspect of the postoperative healing process which is one of the causes of failed back surgery syndrome following spinal surgery. The aim of the present study was to examine the inhibitory effect of 1,4-butanediol diglycidyl ether-crosslinked hyaluronan (cHA) on spinal epidural fibrosis in a swine model. Epidural fibrosis was induced through conduction of hemi-laminotomy (L2 and L3) or laminectomy (L4 and L5), while L1 was assigned as the control group in six pigs. The cHA was applied to L3 and L5 surgical sites. MRI evaluation, histologic examination, expressions of matrix metalloproteinases (MMPs), and cytokines in scar tissue were assessed four months after surgery. cHA treatment significantly decreased the scar formation in both hemi-laminotomy and laminectomy sites. cHA also significantly increased MMP-3 and MMP-9 expression in scar tissue. Further, the epithelial-mesenchymal transition -related factors (transforming growth factor-β and vimentin) were suppressed and the anti-inflammatory cytokines (CD44 and interleukin-6) were increasingly expressed in cHA-treated sites. The current study demonstrated that cHA may attenuate spinal epidural fibrosis formation after laminectomy surgery by enhancing the expression of MMPs and anti-inflammatory pathways.

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