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Erschienen in: European Spine Journal 1/2020

19.10.2019 | Original Article

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

verfasst von: Kun Wang, Xiao long Li, Jinbo Liu, Xiaoliang Sun, Huilin Yang, Xin Gao

Erschienen in: European Spine Journal | Ausgabe 1/2020

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
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Literatur
1.
Zurück zum Zitat Rabb CH (2010) Failed back syndrome and epidural fibrosis. Spine J Off J N Am Spine Soc 10:454–455CrossRef Rabb CH (2010) Failed back syndrome and epidural fibrosis. Spine J Off J N Am Spine Soc 10:454–455CrossRef
2.
Zurück zum Zitat Chandler K, Cappello R (2006) Laminectomy membrane formation in dogs: is the answer still elusive? Vet J 172:1–2CrossRef Chandler K, Cappello R (2006) Laminectomy membrane formation in dogs: is the answer still elusive? Vet J 172:1–2CrossRef
3.
Zurück zum Zitat Jou IM, Tai TW, Tsai CL, Tsai TM, Yung WS, Jung YC (2007) Spinal somatosensory evoked potential to evaluate neurophysiologic changes associated with postlaminotomy fibrosis: an experimental study. Spine 32:2111–2118CrossRef Jou IM, Tai TW, Tsai CL, Tsai TM, Yung WS, Jung YC (2007) Spinal somatosensory evoked potential to evaluate neurophysiologic changes associated with postlaminotomy fibrosis: an experimental study. Spine 32:2111–2118CrossRef
4.
Zurück zum Zitat Kayaoglu CR, Calikoğlu C, Binler S (2003) Re-operation after lumbar disc surgery: results in 85 cases. J Int Med Res 31:318–323CrossRef Kayaoglu CR, Calikoğlu C, Binler S (2003) Re-operation after lumbar disc surgery: results in 85 cases. J Int Med Res 31:318–323CrossRef
5.
Zurück zum Zitat Burton CV, Kirkaldy-Willis WH, Yong-Hing K, Heithoff KB (1981) Causes of failure of surgery on the lumbar spine. Clin Orthop Relat Res 157:191–199 Burton CV, Kirkaldy-Willis WH, Yong-Hing K, Heithoff KB (1981) Causes of failure of surgery on the lumbar spine. Clin Orthop Relat Res 157:191–199
6.
Zurück zum Zitat Sandoval MA, Hernandez-Vaquero D (2008) Preventing peridural fibrosis with nonsteroidal anti-inflammatory drugs. Eur Spine J 17:451–455CrossRef Sandoval MA, Hernandez-Vaquero D (2008) Preventing peridural fibrosis with nonsteroidal anti-inflammatory drugs. Eur Spine J 17:451–455CrossRef
7.
Zurück zum Zitat Lee JY, Stenzel W, Ebel H, Wedekind C, Ernestus RI, Klug N (2004) Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats. J Neurosurg 100(1 Suppl Spine):52–55PubMed Lee JY, Stenzel W, Ebel H, Wedekind C, Ernestus RI, Klug N (2004) Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats. J Neurosurg 100(1 Suppl Spine):52–55PubMed
8.
Zurück zum Zitat Celik S, Altan TS, Goksu K, Ince I, Kapran Z (2008) Mitomycin protection of peridural fibrosis in lumbar disc surgery. J Neurosurg Spine 9:243–248CrossRef Celik S, Altan TS, Goksu K, Ince I, Kapran Z (2008) Mitomycin protection of peridural fibrosis in lumbar disc surgery. J Neurosurg Spine 9:243–248CrossRef
9.
Zurück zum Zitat Songer MN, Ghosh L, Spencer DL (1990) Effects of sodium hyaluronate on peridural fibrosis after lumbar laminotomy and discectomy. Spine 15:550–554CrossRef Songer MN, Ghosh L, Spencer DL (1990) Effects of sodium hyaluronate on peridural fibrosis after lumbar laminotomy and discectomy. Spine 15:550–554CrossRef
10.
Zurück zum Zitat Kato T, Haro H, Komori H, Shinomiya K (2005) Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions. Spine J Off J N Am Spine Soc 5:479–488CrossRef Kato T, Haro H, Komori H, Shinomiya K (2005) Evaluation of hyaluronic acid sheet for the prevention of postlaminectomy adhesions. Spine J Off J N Am Spine Soc 5:479–488CrossRef
11.
Zurück zum Zitat Schimizzi AL, Massie JB, Murphy M, Perry A, Kim CW, Garfin SR (2006) High-molecular- weight hyaluronan inhibits macrophage proliferation and cytokine release in the early wound of a preclinical postlaminectomy rat model. Spine J Off J N Am Spine Soc 6:550–556CrossRef Schimizzi AL, Massie JB, Murphy M, Perry A, Kim CW, Garfin SR (2006) High-molecular- weight hyaluronan inhibits macrophage proliferation and cytokine release in the early wound of a preclinical postlaminectomy rat model. Spine J Off J N Am Spine Soc 6:550–556CrossRef
12.
Zurück zum Zitat Ji GY, Oh CH, Moon BG, Yi S, Han IB, Heo DH (2015) Efficacy and safety of sodium hyaluronate with 1,4-butanediol diglycidyl ether compared to sodium carboxymethylcellulose in preventing adhesion formation after lumbar discectomy. Korean J Spine 12:41–47CrossRef Ji GY, Oh CH, Moon BG, Yi S, Han IB, Heo DH (2015) Efficacy and safety of sodium hyaluronate with 1,4-butanediol diglycidyl ether compared to sodium carboxymethylcellulose in preventing adhesion formation after lumbar discectomy. Korean J Spine 12:41–47CrossRef
13.
Zurück zum Zitat Bolat E, Kocamaz E, Kulahcilar Z, Yilmaz A, Topcu A, Ozdemir M (2014) Investigation of efficacy of mitomycin-C, sodium hyaluronate and human amniotic fluid in preventing epidural fibrosis and adhesion using a rat laminectomy model. Asian Spine J 7:253–259CrossRef Bolat E, Kocamaz E, Kulahcilar Z, Yilmaz A, Topcu A, Ozdemir M (2014) Investigation of efficacy of mitomycin-C, sodium hyaluronate and human amniotic fluid in preventing epidural fibrosis and adhesion using a rat laminectomy model. Asian Spine J 7:253–259CrossRef
14.
Zurück zum Zitat Sabuncuoğlu H, Bavbek M, Sabuncuoğlu B, Gadelha E, Köse K, Preul M (2007) Attenuation of postlaminectomy epidural fibrosis with monoclonal antibodies against intercellular adhesion molecule-1 and CD-18. Spine J 7:459–465CrossRef Sabuncuoğlu H, Bavbek M, Sabuncuoğlu B, Gadelha E, Köse K, Preul M (2007) Attenuation of postlaminectomy epidural fibrosis with monoclonal antibodies against intercellular adhesion molecule-1 and CD-18. Spine J 7:459–465CrossRef
15.
Zurück zum Zitat Semra I, Taşkapılıoğlu MÖ, Fatma OA, Seref D (2015) Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study. J Neurosurg Spine 22:94–100CrossRef Semra I, Taşkapılıoğlu MÖ, Fatma OA, Seref D (2015) Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study. J Neurosurg Spine 22:94–100CrossRef
16.
Zurück zum Zitat Ross JS, Robertson JT, Frederickson RC, Petrie JL, Obuchowski N, Modic MT (1996) Association between peridural scar and recurrent radicular pain after lumbar discectomy: magnetic resonance evaluation. ADCON-L European Study Group. Neurosurgery 38:855–863CrossRef Ross JS, Robertson JT, Frederickson RC, Petrie JL, Obuchowski N, Modic MT (1996) Association between peridural scar and recurrent radicular pain after lumbar discectomy: magnetic resonance evaluation. ADCON-L European Study Group. Neurosurgery 38:855–863CrossRef
17.
Zurück zum Zitat Fritsch EW, Heisel J, Rupp S (1996) The failed back surgery syndrome: reasons, intraoperative findings, and long-term results: a report of 182 operative treatments. Spine 21:626–633CrossRef Fritsch EW, Heisel J, Rupp S (1996) The failed back surgery syndrome: reasons, intraoperative findings, and long-term results: a report of 182 operative treatments. Spine 21:626–633CrossRef
18.
Zurück zum Zitat Robertson JT (1996) Role of peridural fibrosis in the failed back: a review. Eur Spine J 5:S2–S6CrossRef Robertson JT (1996) Role of peridural fibrosis in the failed back: a review. Eur Spine J 5:S2–S6CrossRef
19.
Zurück zum Zitat Hu MH, Yang KC, Sun YH, Chen YC, Yang SH, Lin FH (2017) In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy. Eur Cells Mater 34:307–320CrossRef Hu MH, Yang KC, Sun YH, Chen YC, Yang SH, Lin FH (2017) In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy. Eur Cells Mater 34:307–320CrossRef
20.
Zurück zum Zitat Chen JM, Lee SH, Tsai TT, Niu CC, Chen LH, Chen WJ (2014) Anti-adhesive effect of hyaluronate in a rabbit laminectomy model. Biomed J 37:218–224CrossRef Chen JM, Lee SH, Tsai TT, Niu CC, Chen LH, Chen WJ (2014) Anti-adhesive effect of hyaluronate in a rabbit laminectomy model. Biomed J 37:218–224CrossRef
21.
Zurück zum Zitat Einhaus SL, Robertson JT, Dohan FC, Wujek JR, Ahmad S (1997) Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L). Spine 22:1440–1447CrossRef Einhaus SL, Robertson JT, Dohan FC, Wujek JR, Ahmad S (1997) Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L). Spine 22:1440–1447CrossRef
22.
Zurück zum Zitat De TN, Porchet F, Lutz TW, Gratzl O, Brotchi J, van Alphen HA et al (1998) Clinical assessment of a novel antiadhesion barrier gel: prospective, randomized, multicenter, clinical trial of ADCON-L to inhibit postoperative peridural fibrosis and related symptoms after lumbar discectomy. Am J Orthop 27:111–120 De TN, Porchet F, Lutz TW, Gratzl O, Brotchi J, van Alphen HA et al (1998) Clinical assessment of a novel antiadhesion barrier gel: prospective, randomized, multicenter, clinical trial of ADCON-L to inhibit postoperative peridural fibrosis and related symptoms after lumbar discectomy. Am J Orthop 27:111–120
23.
Zurück zum Zitat Richter HP, Kast E, Tomczak R, Besenfelder W, Gaus W (2001) Results of applying ADCON-L gel after lumbar discectomy: the german ADCON-L study. J Neurosurg Spine 95:179–189CrossRef Richter HP, Kast E, Tomczak R, Besenfelder W, Gaus W (2001) Results of applying ADCON-L gel after lumbar discectomy: the german ADCON-L study. J Neurosurg Spine 95:179–189CrossRef
24.
Zurück zum Zitat Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A (1999) Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: a mouse fibrosis model. J Cell Physiol 181:153–159CrossRef Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A (1999) Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: a mouse fibrosis model. J Cell Physiol 181:153–159CrossRef
25.
Zurück zum Zitat Shinozaki M, Kawara S, Hayashi N, Kakinuma T, Igarashi A, Takehara K (1997) Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta–simultaneous application with basic fibroblast growth factor causes persistent fibrosis. Biochem Biophys Res Commun 240:292–297CrossRef Shinozaki M, Kawara S, Hayashi N, Kakinuma T, Igarashi A, Takehara K (1997) Induction of subcutaneous tissue fibrosis in newborn mice by transforming growth factor beta–simultaneous application with basic fibroblast growth factor causes persistent fibrosis. Biochem Biophys Res Commun 240:292–297CrossRef
26.
Zurück zum Zitat Takehara K (2000) Growth regulation of skin fibroblasts. J Dermatol Sci 24(24 Suppl 1):S70–S77CrossRef Takehara K (2000) Growth regulation of skin fibroblasts. J Dermatol Sci 24(24 Suppl 1):S70–S77CrossRef
27.
Zurück zum Zitat Reed MJ, Vernon RB, Abrass IB, Sage EH (1994) TGF-beta 1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors. J Cell Physiol 158:169–179CrossRef Reed MJ, Vernon RB, Abrass IB, Sage EH (1994) TGF-beta 1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors. J Cell Physiol 158:169–179CrossRef
28.
Zurück zum Zitat Ghahary A, Shen YJ, Scott PG, Gong Y, Tredget EE (1993) Enhanced expression of mRNA for transforming growth factor-beta, type I and type III procollagen in human post-burn hypertrophic scar tissues. J Lab Clin Med 122:465–473PubMed Ghahary A, Shen YJ, Scott PG, Gong Y, Tredget EE (1993) Enhanced expression of mRNA for transforming growth factor-beta, type I and type III procollagen in human post-burn hypertrophic scar tissues. J Lab Clin Med 122:465–473PubMed
29.
Zurück zum Zitat West DC, Hampson IN, Arnold F, Kumar S (1985) Angiogenesis induced by degradation products of hyaluronic acid. Science 228:1324–1326CrossRef West DC, Hampson IN, Arnold F, Kumar S (1985) Angiogenesis induced by degradation products of hyaluronic acid. Science 228:1324–1326CrossRef
30.
Zurück zum Zitat Cencetti C, Bellini D, Longinotti C, Martinelli A, Matricardi P (2011) Preparation and characterization of a new gellan gum and sulphated hyaluronic acid hydrogel designed for epidural scar prevention. J Mater Sci Mater Med 22:263–271CrossRef Cencetti C, Bellini D, Longinotti C, Martinelli A, Matricardi P (2011) Preparation and characterization of a new gellan gum and sulphated hyaluronic acid hydrogel designed for epidural scar prevention. J Mater Sci Mater Med 22:263–271CrossRef
Metadaten
Titel
Using cross-linked hyaluronic acid gel to prevent postoperative lumbar epidural space adhesion: in vitro and in vivo studies
verfasst von
Kun Wang
Xiao long Li
Jinbo Liu
Xiaoliang Sun
Huilin Yang
Xin Gao
Publikationsdatum
19.10.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Spine Journal / Ausgabe 1/2020
Print ISSN: 0940-6719
Elektronische ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-019-06193-w

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