Cell-contact-mediated assembly of contractile airway smooth muscle rings.

Microtissues in the shape of toroidal rings provide an ideal geometry to better represent the structure and function of the airway smooth muscle present in the small airways, and to better understand diseases such as asthma. Here, polydimethylsiloxane devices consisting of a series of circular channels surrounding central mandrels are used to form microtissues in the shape of toroidal rings by way of the self-aggregation and -assembly of airway smooth muscle cell (ASMC) suspensions. Over time, the ASMCs present in the rings become spindle-shaped and axially align along the ring circumference. Ring strength and elastic modulus increase over 14 days in culture, without significant changes in ring size. Gene expression analysis indicates stable expression of mRNA for extracellular matrix-associated proteins, including collagen I and laminins α1 and α4 over 21 days in culture. Cells within the rings respond to TGF-β1 treatment, leading to dramatic decreases in ring circumference, with increases in mRNA expression for collagen I and fibronectin, as well as contraction-associated smooth muscle myosin heavy chain and α-smooth muscle actin. These data demonstrate the utility of ASMC rings as a platform for modeling diseases of the small airways such as asthma.