A high throughput mechanical screening device for cartilage tissue engineering

Abstract

Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying ‘hits’, or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput.

Maximizing cartilage formation and integration via a trajectory-based tissue engineering approach

“…This system would provide for almost continuous analysis of constructs, eliminating the substantial variation in the model and allow for determination of maturation curves from individual specimens as opposed to using different samples at each time point as in this study. Alternatively, high throughput mechanical test systems [38] would allow for many samples to be tested, substantially reducing the time needed for data collection. Our sensitivity analysis suggests that both approaches could easily yield the required information to adequately predict the point at which maturation rate is maximal.…”

Toward understanding the role of cartilage particulates in synovial inflammation

“…These concentrations are previously established for studies of cytokine effects on joint tissues 22–24 . FLS were also cultured ± 250 latex particles per cell to establish a baseline non-biologic particle response.…”

A high-throughput model of post-traumatic osteoarthritis using engineered cartilage tissue analogs

“…Based on the outcomes of single-sample injury, high throughput injury was applied to constructs at 75% strain at 50% strain/sec. For this, a custom high throughput mechanical screening device 26 was used. The device consisted of an aluminum housing with linear bearings to guide the vertical displacement of a loading platen which included a force-sensitive resistor (FSR) array for real-time monitoring of compressive forces during injury.…”

“…Here, we adapted our high throughput mechanical testing system 26 to apply compressive injury to CTAs in a rapid and reproducible manner. The primary goals of this study were to determine the strain and rate dependent response of engineered cartilage to compressive injury, to evaluate the progression of degeneration, and to validate this response with respect to native articular cartilage explants treated similarly.…”