CAREER: Understanding Collagen Microcracks in Soft Tissues Under Normal Body Loads

University Of Connecticut, Storrs CT

Investigators

Abstract

Researchers have extensively characterized sub-millimeter-scale fissures in osteoarthritis, but the PI's lab recently discovered that an impact usually considered non-injurious in fact causes micrometer-scale cracks in collagen of human cartilage. These microcracks may lead to pre-clinical osteoarthritis, but the extent to which they grow under repetitive loads during normal daily activities is unknown. This Faculty Early Career Development (CAREER) Program award supports fundamental research to understand growth of collagen microcracks in soft tissues by validating novel computer simulations with new experimental data. Understanding and modeling cartilage microcracks will likely lead to new therapies and/or lifestyle modification strategies for osteoarthritis patients. Osteoarthritis afflicts nearly 20 percent of the US population; costs over $185.5BN a year (2007); and causes pain, functional limitations, lost earnings and depression, yet we understand neither its cause nor progression. The research will not only characterize one of the earliest observable signs of deterioration likely related to osteoarthritis, but also facilitate studies of other tissues and engineering materials. Moreover, this research will integrate education and outreach to promote interest in science among diverse underrepresented students. Leveraging cartilage as a model system, with availability of healthy and damaged human tissues and longitudinal magnetic reasonance images from the NIH-funded Osteoarthritis Initiative, this award will test the hypothesis that normal physiological loading causes existing cracks of a critical threshold size to propagate in the collagen network of cartilage. To quantify and predict origins of soft tissue damage propagation, the research team will quantify the micro-mechanics of cartilage's constituents; establish image-based, multi-scale simulations; predict microcrack propagation ex vivo; and test prediction sensitivity. Validation studies quantifying microcrack propagation ex vivo will confirm the predictive power of ex vivo and in vivo simulations. Next, the team will predict propagation of cartilage microcracks in vivo under physiological loads, e.g. running, using multi-scale simulations of full knee joints, and test whether areas with increased cartilage microcrack density collocate with cartilage thinning observed in early-stage osteoarthritis. The team will leverage every step to actively engage students. This award will provide: (1) baseline data on microcrack propagation; (2) validated tools to predict local micro-mechanics of damage in porous, fibrous materials from macroscopic deformations; (3) platform technologies to more broadly study mechanical function of fibrous load-bearing tissues (e.g. ligaments) and engineering materials; (4) mechanistic understanding of a likely path to osteoarthritis; (5) new markers to evaluate efficacy of therapies targeting early cartilage degeneration; (6) an educational platform to engage diverse students.