No abstract

There is currently a lack of clinically available solutions to restore functionality to the intervertebral disk (IVD) following herniation injury to the annulus fibrosus (AF). Microdiscectomy is a commonly performed surgical procedure to alleviate pain caused by herniation; however, AF defects remain and can lead to accelerated degeneration and painful conditions. Currently available AF closure techniques do not restore mechanical functionality or promote tissue regeneration, and have risk of reherniation. This review determined quantitative design requirements for AF repair materials and summarized currently available hydrogels capable of meeting these design requirements by using a series of systematic PubMed database searches to yield 1500+ papers that were screened and analyzed for relevance to human lumbar in vivo measurements, motion segment behaviors, and tissue level properties. We propose a testing paradigm involving screening tests as well as more involved in situ and in vivo validation tests to efficiently identify promising biomaterials for AF repair. We suggest that successful materials must have high adhesion strength (∼0.2 MPa), match as many AF material properties as possible (e.g., approximately 1 MPa, 0. 3 MPa, and 30 MPa for compressive, shear, and tensile moduli, respectively), and have high tensile failure strain (∼65%) to advance to in situ and in vivo validation tests. While many biomaterials exist for AF repair, few undergo extensive mechanical characterization. A few hydrogels show promise for AF repair since they can match at least one material property of the AF while also adhering to AF tissue and are capable of easy implantation during surgical procedures to warrant additional optimization and validation.

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.

No abstract