Repair of Herniated Intervertebral Discs: Designing and Translating Annulus Fibrosus Sealants

This thesis developed repairs for the annulus fibrosus (AF). Damaged AF results in altered biomechanical response of the intervertebral disc (IVD), reduced disc height and increased risk of painful reherniation after surgery. The purpose was to address the open clinical problem of AF repair by identifying and screening candidate repairs for successful deploying in a large animal model. For successful translation, the repair must withstand intradiscal pressures up to 2.3 MPa (lifting 20kg) and strains up to 65% (full flexion) and have tensile modulus between 0.5 – 1 MPa and shear modulus 0.1 - 0.3 MP. A newly synthesized, injectable polyethylene glycol block copolymer, TMC3, was screened and had adhesive strength of 0.177 MPa and shear modulus of 0.26 MPa. TMC3 restored range of motion and torsional stiffness of injured intervertebral discs, but extruded at loads lower than human physiologic, highlighting the need for greater adhesion strength. An alternate composite repair, fibrin crosslinked with genipin (FibGen) with and without a space-filling scaffold (Conical), was assessed for torsional response and failure since extrusion is a common failure risk for AF repair. The Conical scaffold failed at lower rotation (5.2 ± 2°) than FibGen (16 ± 5°). The FibGen and Conical repairs had a rate of change of torsional stiffness and torque range above injured but below intact IVDs, indicating improvement. The partial restoration and low herniation risk of FibGen prioritized development of an ovine model of AF injury for preclinical testing. After 1 year, intradiscal blood or osteophytes were present in both FibGen and non-repaired injured IVDs. There were no differences in biomechanical response between treatment groups. These results suggest an AF defect with reduced risk of vertebral body effects could improve the utility of the model for further assessment of FibGen. This thesis established AF repair design requirements and a screening protocol encompassing material and structural tests. It characterized multiple repair strategies, and deployed a promising repair in large animal model. The protocols, material property recommendations, and in vitro and long term in vivo outcomes presented in this thesis advance the pursuit of successful AF repair.

Year	Entry
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1979	Nachemson AL, Schultz AB, Berkson MH. Mechanical properties of human lumbar spine motion segments: influences of age, sex, disc level, and degeneration. Spine. January–February 1979;4(1):1-8.
1999	Wilke H-J, Neef P, Caimi M, Hoogland T, Claes LE. New in vivo measurements of pressures in the intervertebral disc in daily life. Spine. April 15, 1999;24(8):755-762.
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.
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Year

Entry

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.

1986

Miller JAA, Schultz AB, Warwick DN, Spencer DL. Mechanical properties of lumbar spine motion segments under large loads. J Biomech. 1986;19(1):79-84.

1979

Nachemson AL, Schultz AB, Berkson MH. Mechanical properties of human lumbar spine motion segments: influences of age, sex, disc level, and degeneration. Spine. January–February 1979;4(1):1-8.

1999

Wilke H-J, Neef P, Caimi M, Hoogland T, Claes LE. New in vivo measurements of pressures in the intervertebral disc in daily life. Spine. April 15, 1999;24(8):755-762.

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.