Noninvasive Assessment of Glycosaminoglycan Production in Injectable Tissue-Engineered Cartilage Constructs Using Magnetic Resonance Imaging

Abstract

The glycosaminoglycan (GAG) content of engineered cartilage is a determinant of biochemical and mechanical quality. The ability to measure the degree to which GAG content is maintained or increases in an implant is therefore of importance in cartilage repair procedures. The gadolinium exclusion magnetic resonance imaging (MRI) method for estimating matrix fixed charge density (FCD) is ideally suited to this. One promising approach to cartilage repair is use of seeded injectable hydrogels. Accordingly, we assess the reliability of measuring GAG content in such a system ex vivo using MRI. Samples of the photopolymerizable hydrogel, poly(ethylene oxide) diacrylate, were seeded with bovine chondrocytes (*2.4 million cells/sample). The FCD of the constructs was determined using MRI after 9, 16, 29, 36, 43, and 50 days of incubation. Values were correlated with the results of biochemical determination of GAG from the same samples. FCD and GAG were found to be statistically significantly correlated (R 2 = 0.91, p < 0.01). We conclude that MRI-derived FCD measurements of FCD in injectable hydrogels reflect tissue GAG content and that this methodology therefore has potential for in vivo monitoring of such constructs.

Magnetization Transfer Imaging Provides a Quantitative Measure of Chondrogenic Differentiation and Tissue Development

“…This measurement was found to be highly correlated with the GAG content of the construct. 15,33 Recently, to improve contrast in MRI, a Food and Drug Administration-approved superparamagnetic iron oxide contrast agent (Feridex) was used to label chondrocytes and observe the presence of individual cells in tissue-engineered cartilage constructs. 34 Such information is vital to staging and assessing tissue development.…”

“…Therefore, changes in the absolute or relative amounts of CG and PG in different layers of cartilage or in each layer with time can be expected to reflect the biochemical and biomechanical status of engineered cartilage. Over the past decade, MRI has been increasingly used to monitor tissue-engineered constructs, [11][12][13][14][15][16][17] with a great deal of research directed at correlating the CG and PG content with the T 1 and T 2 relaxation times, 18 the apparent diffusion coefficient (ADC), 18 the fixed charge density, 15,19 and the MTR. 3,18 However, to our knowledge, there has not yet been a report applying the qMTI technique to assess the early growth and development of tissueengineered cartilage.…”

Translational Imaging for Regenerative Medicine

“…In addition to cells, SPIONs can be incorporated into engineered scaffolds before implantation, and their location and degradation can be monitored using MRI [17]. Contrast-enhanced, T 1 -weighted imaging by injecting a gadolinium (Gd)-DTPA contrast agent has been used to monitor/measure glycosaminoglycan content during cartilage regeneration [60].…”

CHAPTER 14. Applications of MRI and MRS in Cartilage Therapeutics and Tissue Engineering

“…This demonstrates the potential for non-invasive longitudinal evaluation of matrix production post-implantation. 89 In addition, cell tracking in these gels using MRI has been demonstrated using superparamagnetic iron oxide (SPIO) nanoparticles (see also Chapter 11). SPIO-labeled cells result in hypointense MRI contrast as compared with surrounding tissue due to the iron-induced increase in MRI relaxivity.…”