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

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.
AuthorsCheng-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
JournalScientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 14613 (10 10 2019) ISSN: 2045-2322 [Electronic] England
PMID31601849 (Publication Type: Journal Article)
Chemical References
  • Butylene Glycols
  • Cross-Linking Reagents
  • Hyaluronan Receptors
  • Interleukin-6
  • Transforming Growth Factor beta
  • Vimentin
  • Hyaluronic Acid
  • 1,4-bis(2,3-epoxypropoxy)butane
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
Topics
  • Administration, Topical
  • Animals
  • Butylene Glycols (chemistry)
  • Cicatrix (metabolism)
  • Cross-Linking Reagents (chemistry)
  • Epidural Space (physiopathology)
  • Fibrosis (diagnostic imaging, physiopathology)
  • Hyaluronan Receptors (metabolism)
  • Hyaluronic Acid (administration & dosage)
  • Interleukin-6 (metabolism)
  • Laminectomy
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 3 (metabolism)
  • Matrix Metalloproteinase 9 (metabolism)
  • Models, Animal
  • Swine
  • Transforming Growth Factor beta (metabolism)
  • Vimentin (metabolism)

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