Nondestructive Techniques to Evaluate the Characteristics and Development of Engineered Cartilage

Abstract

In this review, methods for evaluating the properties of tissue engineered (TE) cartilage are described. Many of these have been developed for evaluating properties of native and osteoarthritic articular cartilage. However, with the increasing interest in engineering cartilage, specialized methods are needed for nondestructive evaluation of tissue while it is developing and after it is implanted. Such methods are needed, in part, due to the large inter- and intra-donor variability in the performance of the cellular component of the tissue, which remains a barrier to delivering reliable TE cartilage for implantation. Using conventional destructive tests, such variability makes it near-impossible to predict the timing and outcome of the tissue engineering process at the level of a specific piece of engineered tissue and also makes it difficult to assess the impact of changing tissue engineering regimens. While it is clear that the true test of engineered cartilage is its performance after it is implanted, correlation of pre and post implantation properties determined non-destructively in vitro and/or in vivo with performance should lead to predictive methods to improve quality-control and to minimize the chances of implanting inferior tissue.

Near-Infrared Spectroscopy Predicts Compositional and Mechanical Properties of Hyaluronic Acid-Based Engineered Cartilage Constructs

“…76 Mansour et al and Trachtenberg et al have recently reviewed a comprehensive list of nondestructive evaluation methods used for cartilage and engineered cartilage tissue. 37,77 Kunstar et al used Raman microspectroscopy to study ECM production of primary bovine chondrocytes seeded onto threedimensional scaffolds and assigned two peaks (937 and 1062 cm -1 ) to collagen and proteoglycan, respectively. 78 Although these data are encouraging, there are several challenges in implementing NIR spectral data collection from engineered constructs.…”

“…29 Micro-MRI can yield micron size resolution (and better signal to noise compared to typical clinical imaging), but requires higher field strength, signal averaging, and/or powerful gradient sets, all of which may not be practical in a clinical setting. 37 Contrast-enhanced micro-CT is another option for nondestructive assessment of cartilage proteoglycan content. 38 However, this technique requires the addition of an external contrast agent, which may not be compatible with subsequent implantation of developing constructs.…”

Within or Without You? A Perspective Comparing In Situ and Ex Situ Tissue Engineering Strategies for Articular Cartilage Repair

“…[260] ECM deposition and remodeling can be tracked using reporter gene-based imaging in vivo. [257] 3.6.5. Regulatory Challenges While the regulatory frameworks around new treatments can differ greatly depending on the classification of the medical device, general requirements include regulatory approval, certification of the manufacturing facility, and certification of the quality control processes.…”

“…Only the combined assessment of the balance between the outcomes from different studies and the costs of the products will consolidate the promising results of experimental trials in clinical practice [ 257 ] and will help to determine the specific cohort of eligible patients.…”

Human mesenchymal stem cells induced to differentiate as chondrocytes follow a biphasic pattern of extracellular matrix production

“…Cultured cells secrete matrix molecules, but only a portion of these molecules become entrapped in an insoluble matrix. Most of these secreted molecules, particularly at early stages, are released into conditioned medium as soluble molecules 12,13 . This affords the opportunity to apply proteomic methods to follow differentiation events in a non-invasive manner.…”