Validation and Screening in a High Throughput Mechanical Injury Model of Engineered Cartilage
نویسندگان
چکیده
Introduction Joint injuries increase the likelihood of developing post-traumatic osteoarthritis (PTOA) due to the initiation of catabolic processes that lead to progressive degeneration of the joint cartilage. Several in vitro models have been developed (using chondral explants) to investigate the pathologic mechanisms of PTOA and to evaluate the efficacy of putative small molecule therapeutics to stop or reverse the degenerative process. These agents include antiapoptotic agents that inhibit caspase activity, free-radical scavengers, and polymers that aid in the repair of cell membranes. Unfortunately explant models are limited in their throughput and in the homogeneity of explant response to injury, making larger scale drug screening studies impractical. To address this limitation, we recently developed a high throughput mechanical testing platform capable of applying injurious compression to engineered cartilage constructs, showing increased matrix degradation and cell death comparable to that reported for cartilage injury models. In the current study, we further validated this high throughput mechanical injury (HiTMI) model of PTOA by: 1) directly comparing the response of native chondral explants and engineered cartilage analogs subjected to identical injuries, and 2) using the HiTMI system to evaluate bioactive molecules previously reported to reduce cell death and proteoglycan loss post-injury.
منابع مشابه
Effect of Impact Injury on Engineered Cartilage using a High Throughput Mechanical Screening Device NSF Summer Undergraduate Fellowship in Sensor Technologies
Post-traumatic osteoarthritis (PTOA) occurs when a joint suffers a traumatic injury causing progressive degeneration of the cartilage. Our goal was to develop, in a micro-scale format, methods to mechanically impact native cartilage or cartilage tissue analogs (CTAs) using a high throughput device to initiate the degradative pathways that are associated with PTOA. Our device is designed to meas...
متن کاملPrediction of Engineered Cementitious Composite Material Properties Using Artificial Neural Network
Cement-based composite materials like Engineered Cementitious Composites (ECCs) are applicable in the strengthening of structures because of the high tensile strength and strain. Proper mix proportion, which has the best mechanical properties, is so essential in ECC design material to use in structural components. In this paper, after finding the best mix proportion based on uniaxial tensile st...
متن کاملNootropic Medicinal Plants; Evaluating Potent Formulation By Novelestic High throughput Pharmacological Screening (HTPS) Method
The principle of this method was to screen the pharmacological activity of six prepared polyphyto formulations by using high throughput screening method for their nootropic action. The study was performed in three stages using one, two and three animals, respectively in a group. Test formulations were given p.o daily at the dose of 50 and 100 mg/kg body weight. The test formulations were compar...
متن کاملMultiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow.
Understanding the mechanical environment of articular cartilage and chondrocytes is of the utmost importance in evaluating tissue damage which is often related to failure of the fibre architecture and mechanical injury to the cells. This knowledge also has significant implications for understanding the mechanobiological response in healthy and diseased cartilage and can drive the development of...
متن کاملAdvances in adipose-derived stem cells and cartilage regeneration: review article
The cartilage is a connective tissue that, due to the strength of its extracellular matrix, allows the tissue to tolerate mechanical stress without undergoing permanent deformation. It is responsible for the support of soft tissues and due to its smooth surface and elasticity, gives the joints the ability to slip and bend. excessive weight, excessive activity, or trauma can all cause cartilage ...
متن کامل