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Mechanobiology of Complex Loading in Functional Spinal Units

Hartman, Robert / RAH (2014) Mechanobiology of Complex Loading in Functional Spinal Units. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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A majority of back pain, a costly condition and leading cause of disability, is mechanical in origin involving the intervertebral disc, facet joints, or ligamentum flavum. Mechanical loading may be beneficial or detrimental to spinal tissues depending on loading mode, magnitude, frequency, and duration. Ex vivo mechanobiology systems have been used to explore how axial loading parameters influence intervertebral disc biology, but flexion/extension (F/E) and combined rotations, loading modes relevant to back pain, have not been investigated. Moreover, biological responses in facet cartilage (FC) and ligamentum flavum (LF) have not been studied. A novel experimental platform was developed to assess simultaneous biological responses to six degrees-of-freedom (DOF) loading of intact functional spinal units (FSUs) in annulus fibrosus (AF), nucleus pulposus (NP), FC and LF. A bioreactor previously validated for assessment of axially compressed FSUs was attached to a robotic testing system and validated for rigid fixation and unrestricted movement in F/E and axial torsion (AT). At first, neutral F/E of varying range-of-motion and cycle number was applied. F/E loading elicited a predominantly catabolic response from spinal tissues with significant up-regulation of catabolic gene expression in AF and FC. Range-of-motion modulated aggrecan fragmentation in AF. AT was then added to F/E in small and large magnitudes to simulate mild and severe axial asymmetries treated clinically. F/E with coupled AT was pro-inflammatory in all spinal tissues and was pro-catabolic in AF and LF. In FC, which is gapped by torsion on one side and compressed on the other, pro-inflammatory changes were higher in gapped joints, and catabolic loss of matrix was higher in compressed joints. These findings point to a role for altered segmental mechanics in driving pro-inflammatory, catabolic processes in spinal tissues that may play a role in spinal disorders involved in back pain. Finally, multiple regression analysis was performed to assess how well mechanical responses predicted changes in gene expression. Mechanical predictors accounted for more variation in gene expression in FC and LF than AF and NP. The development of this system provides spine and orthopaedic research with a novel experimental platform that can evaluate complex loading and simulated in vivo motions.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Hartman, Robert / RAHrah30@pitt.eduRAH30
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSowa, Gwendolyn / GASsowaga@upmc.eduGAS26
Committee MemberKang, James /
Committee MemberDebski, Richard / REDgenesis1@pitt.eduGENESIS1
Committee MemberBrown, Bryan /
Date: 19 September 2014
Date Type: Publication
Defense Date: 21 July 2014
Approval Date: 19 September 2014
Submission Date: 24 July 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 389
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Mechanobiology; Flexion-extension; Intervertebral disc; Axial torsion; Facet Cartilage; Ligamentum Flavum
Date Deposited: 19 Sep 2014 17:45
Last Modified: 19 Dec 2016 14:42


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