Dianne Little

Synthetic scaffolds for musculoskeletal tissue engineering: cellular responses to fiber parameters

npj Regenerative Medicine · 2019-06-27 · 233 citations

Tissue engineering often uses synthetic scaffolds to direct cell responses during engineered tissue development. Since cells reside within specific niches of the extracellular matrix, it is important to understand how the matrix guides cell response and then incorporate this knowledge into scaffold design. The goal of this review is to review elements of cell-matrix interactions that are critical to informing and evaluating cellular response on synthetic scaffolds. Therefore, this review examine…

TRPV4-mediated calcium signaling in mesenchymal stem cells regulates aligned collagen matrix formation and vinculin tension

Proceedings of the National Academy of Sciences · 2019-01-23 · 90 citations

Significance The development, repair, and regeneration of anisotropic connective tissues (e.g., tendon, ligament, meniscus) involve deposition of aligned fibrillar collagen by cells. However, the intracellular signaling mechanisms mediating this process are not fully understood. We show that the mechanosensitive cation channel transient receptor potential vanilloid 4 (TRPV4) plays a critical role in controlling aligned collagen assembly by mesenchymal stem cells. Specifically, inhibiting TRPV4 a…

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how)

Journal of Orthopaedic Research® · 2023-08-13 · 35 citations

Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior c…

Transgenic conversion of ω-6 to ω-3 polyunsaturated fatty acids via fat-1 reduces the severity of post-traumatic osteoarthritis

Arthritis Research & Therapy · 2020-04-15 · 31 citations

BACKGROUND: Dietary fatty acid (FA) content has been shown to influence the development of post-traumatic osteoarthritis (PTOA) in obesity. We used the fat-1 transgenic mouse to examine the hypothesis that endogenous reduction of ω-6 to ω-3 FA ratio, under the same dietary conditions, would mitigate metabolic inflammation and the pathogenesis of PTOA in obese male and female mice. METHODS: Male and female fat-1 and wild-type littermates were fed either a control diet or an ω-6 FA-rich high-fat d…

Biological resurfacing in a canine model of hip osteoarthritis

Science Advances · 2021-09-15 · 24 citations

Articular cartilage has unique load-bearing properties but has minimal capacity for intrinsic repair. Here, we used three-dimensional weaving, additive manufacturing, and autologous mesenchymal stem cells to create a tissue-engineered, bicomponent implant to restore hip function in a canine hip osteoarthritis model. This resorbable implant was specifically designed to function mechanically from the time of repair and to biologically integrate with native tissues for long-term restoration. A mass…