In situforming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy
1 Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
2 Department of Orthopaedics, National Taiwan University College of Medicine and National Taiwan University Hospital, No.1, Sec. 1, JenAi Road, Taipei 100, Taiwan
3 School of Dental Technology, College of Oral Medicine, Taipei Medical University, 250 Wuxing Street, Taipei 110, Taiwan
4 Department of Orthopaedics, Far Eastern Memorial Hospital, No.21, Sec. 2, Nanya S. Road, Banciao District, New Taipei City 220, Taiwan
5 Institute of Biomed Engineering and Nanomedicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan
Abstract
Post-operative epidural fibrosis is a biological response after laminectomy that may lead to clinical symptoms, such as radicular pain. An ideal material for prevention of epidural fibrosis should be able to inhibit fibroblast adhesions and reduce formation of scar tissue. An injectable hydrogel would be the material of choice for this purpose, since it could fill an irregular surgical defect completely, gelatein situand be delivered in a minimally-invasive manner. The objective of this study was to evaluate,in vitroandin vivo, the cytocompatibility and anti-adhesive effect of an oxidised hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) hydrogel. Different cell types present in the spine were used to test the cytocompatibility of the hydrogel. The hydrogel extraction medium had no deleterious effects on neural cells (PC-12), but reduced fibroblasts viability (NIH/3T3). Although the hydrogel did not change the release of lactate dehydrogenase from myoblasts (C2C12) and Schwann cells (RSC96), the extraction medium concentration slightly affected the mitochondrial activity of these two cell types. qPCR showed that the hydrogel down-regulated S100a and P4hb expression in NIH/3T3 cells, supporting the hypothesis that the hydrogel might inhibit fibroblast activity. The animal study showed a reduction of scar tissue formation as well as severity of adhesion between scar tissue and the dura mater in a rat laminectomy model. Superficially, the peel-off test showed significantly decreased tenacity. In conclusion, the oxi-HA/ADH hydrogel is a promising injectable and thermosensitive material for prevention of post-operative epidural fibrosis.
Keywords
- Injectable hydrogel
- thermosensitive
- hyaluronic acid
- epidural fibrosis
- laminectomy
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