Degenerative intervertebral disc disease which is irreversible and widespread is an enormous healthcare issue in terms of patient morbidity and societal cost. Non-operative treatment is symptomatic and neither preventative nor restorative. Current, operative intervention for restoration of spine mechanical function is limited to various spinal fusion techniques for endstage disease with varied result in both short and long term outcome. Spinal fusion fails to restore disc motion and mechanical replacement is not a viable clinical option. In this program, the problem of degenerative disc disease is addressed by focusing on the underlying scientific concepts of tissue engineering for a novel treatment in which the nucleus pulposus tissue of the intervertebral disc is regenerated. Hybrid cell-biomaterial constructs in which nucleus pulposus cells are cultured on poly[lactide-co- glycolide] (PLGA) and bioactive glass resorbable substrates are investigated. At the time of hybrid implantation, the biomaterial substrate would provide both biologic and physical support for tissue growth while acting as a spacer for preservation of the intervertebral disc anatomy. With time, the nucleus pulposus would regenerate with elimination of the substrate through biodegradation. The approach is to harvest nucleus pulposus tissue from the host recipient, to isolate and culture nucleus pulposus cells, to introduce these nucleus pulposus cells into the biodegradable, porous substrate of poly[lactide-co- glycolide] and/or bioactive glass and to reimplant this hybrid for reconstruction of the host intervertebral disc. Therefore, the purpose of the program is to test the hypothesis that intervertebral disc function can be restored through regeneration of the nucleus pulposus tissue using a hybrid cell-biomaterial construct.
The specific aims are: 1) to test the hypothesis that a population of nucleus pulposus cells can be expanded in vitro with maintenance of differentiated phenotype, when grown in pellet culture, 2) to examine the suitability of PLGA, bioactive glass, and composites of these as resorbable substrates for vertebral disc reconstruction by assaying mechanical strength, biodegradation and surface properties, 3) to investigate the two-way interaction of the nucleus pulposus cells and the substrates in vitro, and 4) To investigate in vivo the extent of biological and physical restoration of the intervertebral disc when the nucleus pulposus is reconstructed, with constructs of nucleus pulposus cells on PLGA and bioactive glass.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-F (M2))
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University of Pennsylvania
Schools of Medicine
United States
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Yao, Jun; Radin, Shula; S Leboy, Phoebe et al. (2005) The effect of bioactive glass content on synthesis and bioactivity of composite poly (lactic-co-glycolic acid)/bioactive glass substrate for tissue engineering. Biomaterials 26:1935-43
Yao, Jun; Radin, Shula; Reilly, Gwendolen et al. (2005) Solution-mediated effect of bioactive glass in poly (lactic-co-glycolic acid)-bioactive glass composites on osteogenesis of marrow stromal cells. J Biomed Mater Res A 75:794-801
Risbud, Makarand V; Fertala, Jolanta; Vresilovic, Edward J et al. (2005) Nucleus pulposus cells upregulate PI3K/Akt and MEK/ERK signaling pathways under hypoxic conditions and resist apoptosis induced by serum withdrawal. Spine (Phila Pa 1976) 30:882-9
Gan, Jean C; Ducheyne, Paul; Vresilovic, Edward J et al. (2003) Intervertebral disc tissue engineering I: characterization of the nucleus pulposus. Clin Orthop Relat Res :305-14
Risbud, Makarand V; Izzo, Marc W; Adams, Christopher S et al. (2003) An organ culture system for the study of the nucleus pulposus: description of the system and evaluation of the cells. Spine (Phila Pa 1976) 28:2652-8; discussion 2658-9
Gan, Jean C; Ducheyne, Paul; Vresilovic, Edward J et al. (2003) Intervertebral disc tissue engineering II: cultures of nucleus pulposus cells. Clin Orthop Relat Res :315-24
Rajpurohit, Ramesh; Risbud, Makarand V; Ducheyne, Paul et al. (2002) Phenotypic characteristics of the nucleus pulposus: expression of hypoxia inducing factor-1, glucose transporter-1 and MMP-2. Cell Tissue Res 308:401-7
Gan, J C; Ducheyne, P; Vresilovic, E et al. (2000) Bioactive glass serves as a substrate for maintenance of phenotype of nucleus pulposus cells of the intervertebral disc. J Biomed Mater Res 51:596-604
Ducheyne, P; Qiu, Q (1999) Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials 20:2287-303