A device for high-throughput monitoring of degradation in soft tissue samples.

This work describes the design and validation of a novel device, the High-Throughput Degradation Monitoring Device (HDD), for monitoring the degradation of 24 soft tissue samples over incubation periods of several days inside a cell culture incubator. The device quantifies sample degradation by monitoring its deformation induced by a static gravity load. Initial instrument design and experimental protocol development focused on quantifying cartilage degeneration. Characterization of measurement errors, caused mainly by thermal transients and by translating the instrument sensor, demonstrated that HDD can quantify sample degradation with <6 µm precision and <10 µm temperature-induced errors. HDD capabilities were evaluated in a pilot study that monitored the degradation of fresh ex vivo human cartilage samples by collagenase solutions over three days. HDD could robustly resolve the effects of collagenase concentration as small as 0.5 mg/ml. Careful sample preparation resulted in measurements that did not suffer from donor-to-donor variation (coefficient of variance <70%). Due to its unique combination of sample throughput, measurement precision, temporal sampling and experimental versality, HDD provides a novel biomechanics-based experimental platform for quantifying the effects of proteins (cytokines, growth factors, enzymes, antibodies) or small molecules on the degradation of soft tissues or tissue engineering constructs. Thereby, HDD can complement established tools and in vitro models in important applications including drug screening and biomaterial development.

Quantifying Cartilage Biomechanical Properties Using a Linearized Frequency-Domain Method.

Articular cartilage function relies on its unique mechanical behavior. Cartilage mechanics have been described by several analytic models, whose parameters are usually estimated by fitting their constitutive equations to stress-relaxation data. This procedure can be long and is prone to experimental and fitting errors. Τhis study describes a novel methodology for estimating the biomechanical properties of cartilage samples based on their linearized frequency response, derived by applying a series of small-amplitude harmonic displacements superimposed to a bias strain. The proposed methodology, denoted as linearized frequency-domain method (LFM), was demonstrated by quantifying the effects of collagenase and hyaluronidase on cartilage, where it provided robust cartilage parameter estimates that overall agreed well with estimates obtained by stress-relaxation analysis. LFM was also applied to unveil the strain-dependent nature of porcine cartilage biomechanical parameters. Results showed that increasing the bias strain from 5% to 15% caused a significant decrease in cartilage permeability but did not have significant effect on the compression modulus and the Poisson's ratio. Apart from cartilage, LFM can potentially quantify the strain-dependent nature of tissues and biomaterials, thereby enhance tissue-level understanding on organ physiology and pathology, lead to better computational tissue models, and guide tissue engineering research.