Lysophosphatidic Acid: A Novel Biochemical Agent for Tissue Engineering Fibrocartilage

The knee meniscus is a fibrocartilaginous tissue vital to orthopedic health but critically lacking in regenerative capacity. Over 450,000 meniscectomies are performed annually in the US, and such defects are left empty due to the lack of a suitable meniscus replacement. Meniscectomies, however, have been shown to lead to osteoarthritis. Meniscus tissue generated in vitro may greatly improve current clinical methods. Mechanical properties for such tissues are crucial to replacing function since meniscus loading occurs constantly in vivo. Our group has pioneered a scaffold-less self-assembly process to engineer cartilage with compressive properties approaching native values [1, 2]. The tensile properties of this engineered cartilage requires improvement. To do so, we studied the effects of a novel phospholipid growth factor, lysophosphatidic acid (LPA), upon self-assembled meniscus constructs. LPA has been separately shown to induce cell-mediated matrix contraction of collagen gels and maintain cell viability [3, 4], but its use in tissue engineering has been minimal. We hypothesized that LPA would promote cell proliferation in tissue-engineered meniscus constructs as well as enhance tensile properties, and that LPA combined with hydrostatic pressure (HP) stimulation would lead to additional increases in tensile properties.