Feasibility of a Genipin-Crosslinked Fibrin Gel as a Patch for Annulus Fibrosus Repair in the Intervertebral Disc

Abstract

Tears in the annulus fibrosus (AF) of the intervertebral disc are a significant clinical problem resulting in pain and disability for patients. This thesis investigated a tissue engineering solution using fibrin gels crosslinked with genipin and seeded with mesenchymal stem cells to repair defects in the annulus and promote generation of new tissue. The addition of an antifibrinolytic agent was required to maintain gel stability over 30 days, and gel stiffness was significantly increased by the addition of 0.100mg/mL genipin without affecting cell viability. Gene expression indicated that genipin crosslinking upregulated expression of chondrogenic-specific markers. Cells responded to being placed in a defect in tissue and loading may have promoted a more fibrochondrogenic type of lineage differentiation. Histology showed genipin gels promoted a more fibroblastic type of morphology than fibrin gels. Genipin-crosslinked fibrin gels were shown to have sufficient properties for annulus fibrosus repair and should be investigated further.