Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study.
OBJECTIVE
Epidural fibrosis is nonphysiological scar formation, usually at the site of neurosurgical access into the spinal canal, in the intimate vicinity of and around the origin of the radicular sheath. The formation of dense fibrous tissue causes lumbar and radicular pain. In addition to radicular symptoms, the formation of scar tissue may cause problems during reoperation. The authors aimed to investigate the effects of cross-linked high-molecular-weight hyaluronic acid (HA), an HA derivative known as HA gel, on the prevention of epidural fibrosis by using histopathological and biochemical parameters.


METHODS
Fifty-six adult female Sprague-Dawley rats were evaluated. The rats were divided into 4 groups. Rats in the sham group (n = 14) underwent laminectomy and discectomy and received no treatment; rats in the control group (n = 14) underwent laminectomy and discectomy and received 0.9% NaCl treatment in the surgical area; rats in the HA group (n = 14) received HA treatment at the surgical area after laminectomy and discectomy; and rats in the HA gel group (n = 14) underwent laminectomy and discectomy in addition to receiving treatment with cross-linked high-molecular-weight HA in the surgical area. All rats were decapitated after 4 weeks, and the specimens were evaluated histopathologically and biochemically. The results were statistically compared using the Mann-Whitney U-test.


RESULTS
Compared with the sham and control groups, the HA and HA gel groups showed significantly lower fibroblast cell density and tissue hydroxyproline concentrations (p < 0.05). There was statistically significant lower dural adhesion and foreign-body reaction between the control and HA gel groups (p < 0.05). Granulation tissue and epidural fibrosis were significantly lower in the HA and HA gel groups compared with the sham group (p < 0.05). There were no significant differences in any histopathological parameters or biochemical values between Groups 3 and 4 (p > 0.05).


CONCLUSIONS
Cross-linked high-molecular-weight HA had positive effects on the prevention of epidural fibrosis and the reduction of fibrotic tissue density. The efficacy of this agent should also be verified in further experimental and clinical studies.
Department of Neurosurgery, Uludag University Medical School, Bursa, Turkey.
Semra
S
Isık
M Özgür
MÖ
Taşkapılıoğlu
Fatma Oz
FO
Atalay
Seref
S
Dogan
D000818:Animals; D002921:Cicatrix / Q000209:etiology* / Q000517:prevention & control*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004824:Epidural Space / Q000187:drug effects / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D007796:Laminectomy / Q000009:adverse effects*; D008970:Molecular Weight; D017207:Rats, Sprague-Dawley; D012086:Reoperation; D013115:Spinal Canal / Q000473:pathology / Q000601:surgery
D003432:Cross-Linking Reagents; D006820:Hyaluronic Acid
HA = hyaluronic acid; TNF = tissue necrosis factor; cross-linked high-molecular-weight hyaluronic acid; epidural fibrosis; laminectomy