Intervertebral disc degeneration and back pain place a significant burden on veteran health. Pathology of the cartilage and bony endplate adjacent to the disc is observed concomitant with disc degeneration, and is strongly associated with the occurrence of back pain. Despite this, there has been little research effort placed on regeneration of the vertebral endplate in conjunction with the treatment of disc degeneration. The objective of this proposal is to develop and evaluate a composite engineered biologic intervertebral disc and vertebral endplate construct as a strategy for spinal regeneration. This will be accomplished via two specific aims:
Aim 1 : Engineer biologic disc constructs with endplates (eDAPS) at multiple size scales (small animal to human) and evaluate the functional maturation and integration of these constructs with in vitro culture. In this aim, engineered discs will be fabricated at multiple size scales either with (eDAPS) or without (DAPS) the addition of porous polymer foam endplates. Constructs will be seeded with disc cells, and cultured in chemically defined media supplemented with TGF-?3 for up to 15 weeks. At each time point, the functional and compositional maturation of the constructs will be evaluated by MRI T2 mapping, histology, biochemical assays and mechanical testing.
Aim 2 : Determine whether vertebral endplate replacement enhances maintenance of engineered disc (DAPS) structure, composition and nutrition using a pre-clinical rabbit model. For this aim, pre- cultured DAPS alone (no endplate region), or eDAPS with or without hydroxyapaptite incorporated in the endplate region will be implanted in the rabbit lumbar spine for 12 weeks. Construct nutrition, vascularity, composition and mechanical function will be evaluated via in vivo post-contrast enhanced MRI, CT, biochemical assays, histology and mechanical testing. It is anticipated that the results from this research will advance the clinical treatment of pain related to intervertebral disc and vertebral endplate degeneration. The proposed research will be combined with additional training and career development activities, including formal coursework, grant writing workshops, conference presentations, teaching and student mentoring throughout the duration of the career development award period. The research and training activities will be supported by Dr. Gullbrand's dedicated team of mentors, and will position her for success as a future independent faculty member and VA investigator.
The research objective of this proposal is to elucidate the role of the vertebral endplate in a novel treatment strategy for intervertebral disc degeneration, with the aim of advancing veteran care for low back pain and disc degeneration. The proposed research builds on Dr. Gullbrand's previous research experience in animal models, disc nutrition and imaging, while allowing her to develop new skills and expertise in disc biology and tissue engineering. The proposed research is complimentary to the objectives of her mentors' VA-funded research efforts in this area. This Career Development Award proposal identifies a mentoring team, career development and research activities that will support Dr. Gullbrand in transitioning towards a position as an independent VA investigator.
| Gullbrand, Sarah E; Ashinsky, Beth G; Bonnevie, Edward D et al. (2018) Long-term mechanical function and integration of an implanted tissue-engineered intervertebral disc. Sci Transl Med 10: |
| Piazza, Matthew; Peck, Sun H; Gullbrand, Sarah E et al. (2018) Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration. J Orthop Res 36:2771-2779 |
| Gullbrand, Sarah E; Kim, Dong Hwa; Bonnevie, Edward et al. (2018) Towards the scale up of tissue engineered intervertebral discs for clinical application. Acta Biomater 70:154-164 |
