Final Activity Report Summary - NOVODISC (Development of injectable materials for intervertebral disc repair)
Debilitating low back pain as a result of symptomatic lumbar disc degeneration places a significant burden on an industrial society. Surgical treatments involving discectomy followed by fusion of the anterior and posterior spinal elements often result in varied and unpredictable outcomes. At present, there is much interest in using synthetic hydrogels as an alternative therapy for intervertebral implants.
Currently employed synthetic hydrogels have proved to be very effective soft tissue biomaterials for a range of applications, but fail to match the behaviour of natural nucleus pulposus in terms of hydration and osmotic responsiveness. In this study, we have pursued a biomimetic approach employing the sulphonate group as a surrogate for the naturally occurring sulphate in proteoglycans to produce an injectable, in-situ polymerized, osmotically-responsive and non-degradable nucleus pulposus replacement.
Thus we make use of two available precursor monomers: the sodium salt of 2-acrylamido 2, 2 methylpropane sulphonic acid (NaAMPS) and the potassium salt of 2-sulphopropyl acrylate (KSPA) using various compositions. We used an in-house artificially-induced degenerate explant model by injecting enzyme mixture to allow for proteoglycan degeneration prior to the implantation with the PG-analogue. The tailored implant injected matches the behaviour of natural tissue is terms of hydration and ionic responsiveness. It is shown to be biocompatible, as disc and fibroblast cells show no adverse cellular responses to either the monomers or the polymer itself over the concentration ranges which were utilised in this project.
To address issues of visibility, a radio-opaque dye was included in the monomer mixture which appeared not to change the rheological properties. Preliminary biomechanical tests showed stability of the implant within the nucleus pulposus cavity. Using this approach, we aim to demonstrate the potential for a novel, biomimetic and minimally invasive treatment for a rapid repair and replacement of damaged intervertebral disc in cases of competent annulus fibrosus, greatly reducing the risk of a spinal surgery.
Currently employed synthetic hydrogels have proved to be very effective soft tissue biomaterials for a range of applications, but fail to match the behaviour of natural nucleus pulposus in terms of hydration and osmotic responsiveness. In this study, we have pursued a biomimetic approach employing the sulphonate group as a surrogate for the naturally occurring sulphate in proteoglycans to produce an injectable, in-situ polymerized, osmotically-responsive and non-degradable nucleus pulposus replacement.
Thus we make use of two available precursor monomers: the sodium salt of 2-acrylamido 2, 2 methylpropane sulphonic acid (NaAMPS) and the potassium salt of 2-sulphopropyl acrylate (KSPA) using various compositions. We used an in-house artificially-induced degenerate explant model by injecting enzyme mixture to allow for proteoglycan degeneration prior to the implantation with the PG-analogue. The tailored implant injected matches the behaviour of natural tissue is terms of hydration and ionic responsiveness. It is shown to be biocompatible, as disc and fibroblast cells show no adverse cellular responses to either the monomers or the polymer itself over the concentration ranges which were utilised in this project.
To address issues of visibility, a radio-opaque dye was included in the monomer mixture which appeared not to change the rheological properties. Preliminary biomechanical tests showed stability of the implant within the nucleus pulposus cavity. Using this approach, we aim to demonstrate the potential for a novel, biomimetic and minimally invasive treatment for a rapid repair and replacement of damaged intervertebral disc in cases of competent annulus fibrosus, greatly reducing the risk of a spinal surgery.