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

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.

Year	Entry
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Year

Entry

2003

Urban JPG, Roberts S. Degeneration of the intervertebral disc. Arthritis Res Ther. 2003;5(3):120-130.

1996

Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest. August 15, 1996;98(4):996-1003.

2005

Stokes IAF, Iatridis JC. Biomechanics of the spine. In: Mow VC, Huiskes R, eds. Basic Orthopaedic Biomechanics & Mechano-Biology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:529-561.

1999

Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet. May 1999;22(1):85-89.

1975

Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat. September 1975;120(1):113-130.