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Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model

ABSTRACT Post‐laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an important cause of failed back syndrome (FBS). The various clinical approaches used to control EF yield mixed outcomes. Cross‐linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability a...

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Published in:Journal of orthopaedic research 2016-02, Vol.34 (2), p.299-306
Main Authors: Wu, Cheng-Yi, Huang, Yi-Hung, Lee, Jung-Shun, Tai, Ta-Wei, Wu, Po-Ting, Jou, I-Ming
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description ABSTRACT Post‐laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an important cause of failed back syndrome (FBS). The various clinical approaches used to control EF yield mixed outcomes. Cross‐linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability and residence time. We evaluated the therapeutic attenuation of proliferative EF in laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11‐L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10 each) of Sprague‐Dawley rats and then histologically examined 2 months post‐surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III) laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the diameters within the spinal canal, dura mater thickness, and the area of the epidural space, subarachnoid space, and conus medullaris space were assessed. The cHA‐treated subgroups (I, III) had a significantly lower grade of EF, thinner dura mater, and larger epidural and subarachnoid spaces than did the control subgroups (II, IV) (p 
doi_str_mv 10.1002/jor.23001
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The various clinical approaches used to control EF yield mixed outcomes. Cross‐linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability and residence time. We evaluated the therapeutic attenuation of proliferative EF in laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11‐L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10 each) of Sprague‐Dawley rats and then histologically examined 2 months post‐surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III) laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the diameters within the spinal canal, dura mater thickness, and the area of the epidural space, subarachnoid space, and conus medullaris space were assessed. The cHA‐treated subgroups (I, III) had a significantly lower grade of EF, thinner dura mater, and larger epidural and subarachnoid spaces than did the control subgroups (II, IV) (p &lt; 0.05). The cHA formed a solid interpositional membrane barrier that prevented invasive fibrosis, and also helped reduce pathological changes to the adjacent structures. In conclusion, topically applied cHA is effective for reducing EF. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:299–306, 2016.</description><identifier>ISSN: 0736-0266</identifier><identifier>EISSN: 1554-527X</identifier><identifier>DOI: 10.1002/jor.23001</identifier><identifier>PMID: 26222496</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; cross-linked hyaluronic acid hydrogel (cHA) ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Dura Mater - pathology ; epidural fibrosis (EF) ; Failed Back Surgery Syndrome - prevention &amp; control ; Fibrosis - prevention &amp; control ; Hyaluronic Acid - administration &amp; dosage ; Laminectomy ; laminotomy ; Male ; Random Allocation ; Rats, Sprague-Dawley ; Spinal Canal - pathology ; spine ; Viscosupplements - administration &amp; dosage</subject><ispartof>Journal of orthopaedic research, 2016-02, Vol.34 (2), p.299-306</ispartof><rights>2015 Orthopaedic Research Society. 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Orthop. Res</addtitle><description>ABSTRACT Post‐laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an important cause of failed back syndrome (FBS). The various clinical approaches used to control EF yield mixed outcomes. Cross‐linked hyaluronic acid hydrogel (cHA) was synthesized to increase mechanical stability and residence time. We evaluated the therapeutic attenuation of proliferative EF in laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11‐L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10 each) of Sprague‐Dawley rats and then histologically examined 2 months post‐surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III) laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the diameters within the spinal canal, dura mater thickness, and the area of the epidural space, subarachnoid space, and conus medullaris space were assessed. The cHA‐treated subgroups (I, III) had a significantly lower grade of EF, thinner dura mater, and larger epidural and subarachnoid spaces than did the control subgroups (II, IV) (p &lt; 0.05). The cHA formed a solid interpositional membrane barrier that prevented invasive fibrosis, and also helped reduce pathological changes to the adjacent structures. In conclusion, topically applied cHA is effective for reducing EF. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:299–306, 2016.</description><subject>Animals</subject><subject>cross-linked hyaluronic acid hydrogel (cHA)</subject><subject>Disease Models, Animal</subject><subject>Drug Evaluation, Preclinical</subject><subject>Dura Mater - pathology</subject><subject>epidural fibrosis (EF)</subject><subject>Failed Back Surgery Syndrome - prevention &amp; control</subject><subject>Fibrosis - prevention &amp; control</subject><subject>Hyaluronic Acid - administration &amp; dosage</subject><subject>Laminectomy</subject><subject>laminotomy</subject><subject>Male</subject><subject>Random Allocation</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal Canal - pathology</subject><subject>spine</subject><subject>Viscosupplements - administration &amp; dosage</subject><issn>0736-0266</issn><issn>1554-527X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kEtv1DAUhS0EokNhwR9AXsIiHT_iR5ZQlfKoKCog2FmOfVPcOnFqZ4CIP09mpu2O1T1X-s63OAg9p-SIEsLWVykfMU4IfYBWVIi6Ekz9eIhWRHFZESblAXpSyhUhRFGmH6MDJhljdSNX6O9J1wVn3YxTh6c0Ljlil1MpVQzDNXj8c7Zxk9MQHLYubH-f0yVEHAY8ZvgFwxSGSzymMuFo-zCAm1I_r3c5bSPuQrsYQ9lWLM52wn3yEJ-iR52NBZ7d3kP07e3J1-N31dn56fvj12eVq6WmlfNtw70gulXKW-frVjPR1qQlzHmiO6F9I6DlSnpqG8moE4IzgLrWtgMt-CF6ufeOOd1soEymD8VBjHaAtCmGKkkaTqVuFvTVHt1NkKEzYw69zbOhxGy3NsvWZrf1wr641W7aHvw9eTfuAqz3wO8QYf6_yXw4v7hTVvtGKBP8uW_YfG2k4kqY759ODWUf68_kyxtzwf8BO0SaJA</recordid><startdate>201602</startdate><enddate>201602</enddate><creator>Wu, Cheng-Yi</creator><creator>Huang, Yi-Hung</creator><creator>Lee, Jung-Shun</creator><creator>Tai, Ta-Wei</creator><creator>Wu, Po-Ting</creator><creator>Jou, I-Ming</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201602</creationdate><title>Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model</title><author>Wu, Cheng-Yi ; Huang, Yi-Hung ; Lee, Jung-Shun ; Tai, Ta-Wei ; Wu, Po-Ting ; Jou, I-Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4681-cdb93d508b77dacd4b825b40b02cd08f58d95eb376d1a9621c5532ee448afe853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>cross-linked hyaluronic acid hydrogel (cHA)</topic><topic>Disease Models, Animal</topic><topic>Drug Evaluation, Preclinical</topic><topic>Dura Mater - pathology</topic><topic>epidural fibrosis (EF)</topic><topic>Failed Back Surgery Syndrome - prevention &amp; control</topic><topic>Fibrosis - prevention &amp; control</topic><topic>Hyaluronic Acid - administration &amp; dosage</topic><topic>Laminectomy</topic><topic>laminotomy</topic><topic>Male</topic><topic>Random Allocation</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Canal - pathology</topic><topic>spine</topic><topic>Viscosupplements - administration &amp; dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Cheng-Yi</creatorcontrib><creatorcontrib>Huang, Yi-Hung</creatorcontrib><creatorcontrib>Lee, Jung-Shun</creatorcontrib><creatorcontrib>Tai, Ta-Wei</creatorcontrib><creatorcontrib>Wu, Po-Ting</creatorcontrib><creatorcontrib>Jou, I-Ming</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of orthopaedic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Cheng-Yi</au><au>Huang, Yi-Hung</au><au>Lee, Jung-Shun</au><au>Tai, Ta-Wei</au><au>Wu, Po-Ting</au><au>Jou, I-Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model</atitle><jtitle>Journal of orthopaedic research</jtitle><addtitle>J. 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subjects Animals
cross-linked hyaluronic acid hydrogel (cHA)
Disease Models, Animal
Drug Evaluation, Preclinical
Dura Mater - pathology
epidural fibrosis (EF)
Failed Back Surgery Syndrome - prevention & control
Fibrosis - prevention & control
Hyaluronic Acid - administration & dosage
Laminectomy
laminotomy
Male
Random Allocation
Rats, Sprague-Dawley
Spinal Canal - pathology
spine
Viscosupplements - administration & dosage
title Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post laminectomy/laminotomy fibrosis in a rat model
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