The influence of exogenous cross-linking and compressive creep loading on intradiscal pressure

Abstract

This study involves a biomechanical evaluation of a prospective injectable treatment for degenerative discs. The high osmolarity of the non-degenerated nucleus pulposus attracts water contributing to the hydrostatic behavior of the tissue. This intradiscal pressure is known to drop as fluid is exuded from the matrix due to compressive loading. The objective of this study was to compare the changes in intradiscal pressure in control and genipin cross-linked intervertebral discs. Thirty bovine lumbar motion segments were randomly divided into a phosphate-buffered saline control group and a 0.33% genipin group and soaked at room temperature for 2 days. A needle pressure sensor was held in the center of the disc while short-term and static creep compressive loads were applied. The control group demonstrated a 25% higher average intradiscal pressure compared to genipin-treated discs under 750 N compressive load (p=0.029). Depressurization during static compressive creep was 56% higher in the control than in the genipin group (p=0.014). These results suggest cross-linking induced changes in the poroelastic properties of the involved tissues affected the mechanics of compressive load support in the disc with lower levels of nucleus pressure, a corresponding decrease in the elastic expansion of the annulus, and an increased axial compressive loading of the inner and outer annulus tissues. It is possible that concurrent changes in hydraulic permeability and proteoglycan retention known to be associated with genipin cross-linking were also contributors to poroelastic changes. Reduction of peak pressures and moderation of pressure fluctuations could be beneficial relative to discogenic pain.

Influence of Cervical Spine Position, Turning Time, and Cervical Segment on Cadaver Intradiscal Pressure During Cervical Spinal Manipulative Therapy

“…Our experimental results reveal that different cervical positions during SMT substantially influence IDP, which reduce gradually through flexion 20°, flexion 10°, neutral position, extension 10°to extension 20°. This is similar to lumbar flexion causing higher IDP than lumbar extension 43 and other studies that reported a direct link between increased lumbar flexion and increased IDP in sitting. [44][45][46][47][48] Furthermore, higher IDP was equated with higher risk of annulus rupture and low back pain because tensile stress to annulus fibers was mainly equated with compressive load.…”

Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs

“…Soaking was used rather than injections of reagent in order to minimize variation of treatment coverage, which could potentially mask the treatment effects. A previous study verified that soaking treatment does not affect disc tissue hydration [ 33 ].…”

“…In a previous study investigating the exogenous crosslinking effects on IDP, it was noted that IDP was lower in genipin-crosslinked disc specimens under axial compressive load and that the drop in IDP caused by creep loading was decreased [ 33 ]. In seeming opposition, another work revealed that genipin crosslinking doubled fluid flow into and out of the NP following compressive creep loading and recovery [ 29 ].…”

“…Combined with the previously determined anisotropic material properties, these data enabled calculation of tissue stresses and exogenous-crosslinking-induced changes in load sharing. An experimental model under static creep loading was chosen to both be consistent with previous studies [ 29 , 33 ] and provide an indication of load sharing changes at differing levels of disc fluid content.…”

Consecutive Applications of Protein Crosslinking Reagents to Intervertebral Disc Annulus Fibrosus Results in a Cumulative Increase in Crosslinking

“…Genipin is a deglycosylated derivative of geniposide, which itself is a naturally occurring component of gardenia seed pods, and is capable of crosslinking proteins by self-polymerization and crosslinking of protein-bound primary amines (predominantly of lysine and arginine residues). 13 It has been shown that GP treatment of the intervertebral disc can address several of the underlying problems related to back pain and disability, including nutritional deficiency, joint stability, disc bulge, 12,[14][15][16][17] and, most recently, loss of proteoglycans. 18 One potential drawback of this approach is the limited solubility of GP in aqueous solutions such as ones previously developed to optimize its reaction kinetics.…”