Herniated intervertebral discs are a common cause of back and neck pain. There is an unmet clinical need to seal annulus fibrosus (AF) defects, since discectomy surgeries address acute pain but are complicated by reherniation and recurrent pain. Copolymers of polyethylene glycol with trimethylene carbonate (TMC) and hexamathylene diisocyanate end-groups were formulated as AF sealants since the hexamathylene diisocyanate form covalent bonds with native AF tissue. TMC adhesives were evaluated and optimized using the design criteria: stable size, strong adherence to AF tissue, high cytocompatibility, restoration of intervertebral disc biomechanics to intact levels following in situ repair, and low extrusion risk. TMC adhesives had high adhesion strength as assessed with a pushout test (150 kPa), and low degradation rates over three weeks in vitro. Both TMC adhesives had shear moduli (220 & 490kPa) similar to, but somewhat higher than AF tissue. The adhesive with three TMC moieties per branch (TMC3) was selected for additional in situ testing because it best matched AF shear properties. TMC3 restored torsional stiffness, torsional hysteresis area and axial range of motion to intact states. However, in a failure test of compressive deformation under fixed 5° flexion, some herniation risk was observed with failure strength of 5.9 MPa compared to 13.5 MPa for intact samples; TMC3 herniated under cyclic organ culture testing. These TMC adhesives performed well during in vitro and in situ testing, but additional optimization to enhance failure strength is required to further this material to advanced screening tests such as long term degradation.
|Journal||Journal of tissue engineering and regenerative medicine|
|Publication status||Published - 1 Feb 2018|