Validation and Screening in a High Throughput Mechanical Injury Model of Engineered Cartilage

نویسندگان

  • Bhavana Mohanraj
  • Rodolfo Finocchi
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.

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تاریخ انتشار 2014