Peer-Reviewed Journal Details
Mandatory Fields
Likhitpanichkul, M., Kim, Y., Torre, O.M., See, E., Kazezian, Z., Pandit, A., Hecht, A.C. and Iatridis, J.
The Spine Journal
Fibrin-genipin Annulus Fibrosus Sealant as a Delivery System for Anti-TNFα Drug
Optional Fields
Intervertebral disc; Annulus fibrosus repair; Biomaterials; Anti-inflammatory drug; Drug delivery; Spinal injection
BACKGROUND CONTEXT: Intervertebral discs (IVDs) are attractive targets for local drug delivery because they are avascular structures with limited transport. Painful IVDs are in a chronic inflammatory state. Although anti-inflammatories show poor performance in clinical trials, their efficacy treating IVD cells suggests that sustained, local drug delivery directly to painful IVDs may be beneficial. PURPOSE: The purpose of this study was to determine if genipin cross-linked fibrin (FibGen) with collagen Type I hollow spheres (CHS) can serve as a drug-delivery carrier for infliximab, the antitumor necrosis factor a (TNFa) drug. Infliximab was chosen as a model drug because of the known role of TNFa in increasing downstream production of several pro-inflammatory cytokines and pain mediators. Genipin cross-linked fibrin was used as drug carrier because it is adhesive, injectable, and slowly degrading hydrogel with the potential to seal annulus fibrosus (AF) defects. CHS allow simple and nondamaging drug loading and could act as a drug reservoir to improve sustained delivery. STUDY DESIGN/SETTING: This is a study of biomaterials and human AF cell culture to determine drug release kinetics and efficacy. METHODS: Infliximab was delivered at low and high concentrations using FibGen with and without CHS. Gels were analyzed for structure, drug release kinetics, and efficacy treating human AF cells after release. RESULTS: Fibrin showed rapid infliximab drug release but degraded quickly. CHS alone showed a sustained release profile, but the small spheres may not remain in a degenerated IVD with fissures. Genipin cross-linked fibrin showed steady and low levels of infliximab release that was increased when loaded with higher drug concentrations. Infliximab was bound in CHS when delivered within FibGen and was only released after enzymatic degradation. The infliximab released over 20 days retained its bioactivity as confirmed by the sustained reduction of interleukin (IL)-1b, IL-6, IL-8, and TNFa concentrations produced by AF cells.
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