Ex Vivo Explant Models: Unique Insights Offered by Studying Disease in a Dish

: At first glance, tendon may seem to be a relatively simple tissue with the straightforward function of transferring muscle forces to the bony skeleton. A closer look reveals that it is actually a complex physiological system, with tightly coordinated interplay between an “intrinsic compartment” comprising the fibrous collagen core (tendon cells and the multiscale arrangement of collagen assemblies), and an “extrinsic tendon compartment” consisting of synovium-like tissues that interface with the immune, vascular, and nervous systems. The extent of intrinsic and extrinsic compartment coordination in functional repair, and discord in degenerative processes, is still poorly understood. In this workshop segment, we aim to make the case that explant models from rodent tail tendon provide a powerful platform to identify, investigate and understand aspects of the complex cellular and cell-matrix interplay in tendon tissue, and offer potential to reveal central mechanisms of connective tissue homeostasis and repair. Background: Tendon is an under-researched tissue, a fact that that can be at least partly attributed to a shortage of physiologically and clinically relevant research models. Almost all existing data regarding basic mechanisms of tissue physiology or tendon damage and repair thus stem either from a limited range of non-primate animal models or from in vitro experiments on isolated animal or human tendon cells in 2D or 3D tissue culture. Although 2D and 3D culture systems are widely used due to their practicality, these experimental models are really only amenable to the study of robust cellular mechanisms that are realtively insensitive to physiological context and/or subtleties of the biochemical and biophysical cellular niche. The physiological contexts that 2D and 3D adequately capture arguably include neotendon formation after an acute injury, or the study of acute interactions between recruited tendon cells and an implanted biomaterial. In contrast, the physiological contexts of tendon tissue homeostasis, disease, and repair of focal tissue damage involves cellular niches in which the extracellular matrix (ECM) architecture, ECM biophysics, context dependent cell-matrix interactions, and spatially regulated cell-cell