Correlating Material Properties with Tissue Composition in Enzymatically Digested Bovine Annulus Fibrosus and Nucleus Pulposus Tissue

Abstract

Aging and degeneration of the intervertebral disk are accompanied by decreases in water and proteoglycan contents, and structural alterations. The aim of this study was to determine the impact of compositional changes on the material properties of intervertebral disk tissues. Confined compression stress-relaxation experiments were applied to bovine caudal annulus fibrosus and nucleus pulposus tissue specimens that were separated into three experimental groups: in situ, free-swelling control (PBS), and digestion (chondroitinase-ABC). Measurements of glycosaminoglycan (GAG) and water content, as well as nonlinear finite deformation biphasic theory and multiple linear regression analyses were performed. The compressive modulus HA0 and permeability k0 of in situ specimens were 0.37+/-0.06 MPa and 0.49+/-0.08x10(-15) m4 N-1 s-1 for nucleus, and 0.74+/-0.13 MPa and 0.42+/-0.05x10(-15) m4 N-1 s-1 for annulus, respectively. There was a larger effect of swelling and digestion on the material properties and biochemical composition of nucleus pulposus than for annulus fibrosus. Alterations in proteoglycan and water content affected the compressive modulus and permeability, although the permeability was somewhat more strongly affected by water content than by proteoglycan content. Correlation coefficients r<or=0.75 for the multiple regression indicated water and GAG content can moderately predict material properties, however other compositional and structural factors must be considered.

An In Vivo Model of Reduced Nucleus Pulposus Glycosaminoglycan Content in the Rat Lumbar Intervertebral Disc

“…Specifically, studies have shown hypermobility at low loads 34 and altered viscoelastic properties including increased creep rate and deformation 35 in early degeneration, mechanical changes that are attributed to the reduction in nucleus glycosaminoglycan. 5,7,8,36 At 4 weeks postinjection, neutral zone modulus, range of motion, and creep were all altered in a manner consistent with the expected changes in a degenerating disc, and were altered to the same degree as observed after an equivalent ChABC injection in vitro. Further, both neutral zone modulus and range of motion were linearly correlated with nucleus glycosaminoglycan content 4 weeks postinjection-relationships that were identical to those determined in the absence of biologic activity.…”

“…[2][3][4] This reduction of glycosaminoglycan content has an impact on the mechanical function of the disc: the ability to imbibe and bind water is diminished, pressure within the nucleus is decreased, and ultimately, the mechanical function of the nucleus and the entire motion segment is altered. [5][6][7][8] It is plausible that progressive degeneration follows this reduced glycosaminoglycan content and altered mechanics, yet this ultimately remains a hypothesis, and knowledge of specific mechanisms and interactions is limited. To this end, in vivo animal models simulating the condition of decreased nucleus pulposus glycosaminoglycan content as observed in early degeneration would be of great utility.…”

Age- and degeneration-related variations in cell density and glycosaminoglycan content in the human cervical intervertebral disc and its endplates

“…Recent years have seen a multitude of studies focusing on the analysis of changes in the extracellular matrix of the IVD during ageing [4,5,7,13,14,15,16,17,18]. However, despite tremendous research efforts, we still lack knowledge regarding cell density and GAG content throughout the IVD.…”

“…The youngest specimen in our study came from a 19-year-old person. This prevented us from analyzing how cell density and GAG content change during the years (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) when the IVD and the endplates undergo the greatest changes.…”

“…The correct spatial distribution of proteoglycans (with glycosaminoglycan chains -GAG) in the IVD is crucial for the discs' physiological swelling behaviors, streaming potential, and compressive properties [13]. During IVD degeneration, proteolytic fragmentation of large and small proteoglycans may induce or inhibit essential inflammatory response pathways, altering the ability of the extracellular matrix to maintain its structural integrity [14,15].…”