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Development of an Intervertebral Disc Mechanobiological System

Hartman, Robert A (2011) Development of an Intervertebral Disc Mechanobiological System. Master's Thesis, University of Pittsburgh. (Unpublished)

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Intervertebral disc degeneration is a leading cause of low back pain, a significant socioeconomic burden with a broad array of costly treatment options. Motion-based therapy has shown modest efficacy in treating LBP. Basic science research has begun to identify thresholds of beneficial and detrimental mechanical loading of the intervertebral disc. Ex-vivo mechanobiological systems are important experimental models for determining the effect of loading parameters on disc biology and matrix homeostasis. A novel experimental platform has been developed to facilitate in-situ loading of a rabbit functional spinal unit (FSU) with outcome measures relevant to disc matrix homeostasis and cell behavior. First, the system was designed for multi-axis motion outside of an incubator and validated for rigid fixation and stable, physiologic environmental conditions that maintained adequate cell viability. Following system development and validation, experimental testing on rabbit FSUs proceeded with cyclic compression and four-hour constant compression compared. Disc tissue was analyzed for cell viability using a colorimetric absorbance assay or relative gene expression. Conditioned media was assayed for matrix metalloproteinase activity, type-II collagen degradation fragments, prostaglandins, and an aggrecan epitope implicated in aggrecan synthesis. Cell viability remains high (>90%) regardless of loading. Relative gene expression shows small increases in anabolism and larger, variable increases in catabolic and inflammatory markers. These trends are more reliable in AF than NP. Interestingly, matrix metalloproteinase activity trends toward a decrease in media in loaded specimen culture. Although type-II collagen fragment concentrations do not correlate with loading, the aggrecan synthesis marker concentrations do. Results indicate increased catabolism and aggrecan turnover in response to loading, though the net effect on matrix homeostasis at later time points is unclear. Future work will explore applying other loading patterns, rotational loading, and coupling local inflammatory stimuli with loading. This novel experimental platform will explore the effect of physiologic motion simulations on disc homeostasis, helping to improve motion-based therapies.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Hartman, Robert Arah30@pitt.eduRAH30
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSowa, Gwendolyn Asowaga@upmc.eduGAS26
Committee MemberKang, James
Committee MemberDebski, Richard Erdebski@engr.pitt.eduGENESIS1
Date: 26 January 2011
Date Type: Completion
Defense Date: 16 November 2010
Approval Date: 26 January 2011
Submission Date: 22 November 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: MSBeng - Master of Science in Bioengineering
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: biomechanics; CS-846; disc biomarkers; dissolved oxygen; fixture rigidity; flexible bioreactor; intradiscal pressure; MMP-3; organ culture; PGE2; temperature control; CTX-II; MMP-1
Other ID:, etd-11222010-104529
Date Deposited: 10 Nov 2011 20:05
Last Modified: 19 Dec 2016 14:37


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