Myofibroblast Inhibition to Prevent Posttraumatic Joint Contracture.

摘要

Fibrosis in the joints of the extremities is due to the action of myofibroblasts, cells activated by the inflammatory cascade of injury to effect scarring and contracture. There is as yet no medical or pharmaceutical adjuvant therapy that can prevent or treat scar contracture in the joint. We postulate that molecular inhibition of myofibroblasts will mitigate scarring and contracture in a rabbit model of post-traumatic knee arthrofibrosis. The goal is to use small interfering RNAs as therapeutic agents, delivered through non-viral means. We have thus far established a baseline model of scar contracture across the knee joint in the rabbit hindleg that mimics a typical human clinical course: injury, followed by a period of fixation (8 weeks), followed by an extended period of release (16 weeks). We note marked contracture in the injured, operated joint, with none in the contralateral control hindlimb. Histologic and initial molecular analysis confirms dense intracapsular scar formation in the injured joints compared to contralateral control. These findings establish a significant baseline of injury against which our intervention may be measured.