In vitro and biomechanical screening of polyethylene glycol and poly(trimethylene carbonate) block copolymers for annulus fibrosus repair

Abstract

Abstract: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.

Enhancement of Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Devices

“…Recent studies have shown that several biomaterials implanted for closure of AF defects maintain the height and stability of the IVD [29–31]. Since there are ample nutrient supplies at the edges of AF due to blood supply, porous materials with high transport properties implanted in AF can be designed to facilitate transport of nutrients from the edge of AF into the NP region in order to promote cellular energy production.…”

Multi-laminate Annulus Fibrosus Repair Scaffold with an Interlamellar Matrix Enhances Impact Resistance, Prevents Herniation and Assists in Restoring Spinal Kinematics

“…(Cruz et al, 2018;R. Long et al, 2016;Long et al, 2017) Additionally, while other studies using similar AF repair biomaterials have demonstrated the ability to resist expulsion from the AF focal defect, a substantial portion of native NP tissue is often removed which in turn may presumably reduce the IVD pressurization. (Cruz et al, 2018;Likhitpanichkul et al, 2014) Therefore, these AF repair biomaterials may not be exposed to the full magnitude of radially-directed loading following the removal of native NP tissue.…”

Feasibility of the annulus fibrosus repair with in situ gelating hydrogels – A biomechanical study

“…Parameters evaluated for compressive testing included compressive stiffness and disc height at each repeated test. Compressive stiffness was defined as the slope of the linear fit to the last 20% position of the force-position signal [19,33]. Initial disc height was measured on plain radiographs by averaging the shortest distances between endplates on antero-posterior and lateral view.…”