Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells

Abstract

Mechanical effects on cells have received more and more attention in the studies of tissue engineering, cellular pathogenesis, and biomedical device design. Anisotropic biaxial cyclic stress, reminiscent of the in vivo cellular mechanical environment, may promise significant implications for biotechnology and human health. We have designed, fabricated and characterized a microdevice that imparts a variety of anisotropic biaxial cyclic strain gradients upon cells. The device is composed of an elastic membrane with microgroove patterns designed to associate cell orientation axes with biaxial strain vectors on the membrane and a Flexcell stretcher with timely controlled vacuum pressure. The stretcher generates strain profile of anisotropic biaxial microgradients on the membrane. Cell axes determined by the microgrooves are associated with the membrane strain profile to impose proper biaxial strains on cells. Using vascular smooth muscle cells as a cell model, we demonstrated that the strain anisotropy index of a cell was likely one of the determinant mechanical factors in cell structural and functional adaptations. The nuclear shape and cytoskeleton structure of smooth muscle cells were influenced by mechanical loading, but were not significantly affected by the strain anisotropy. However, cell proliferation has profound responses to strain anisotropy.

High pulsatility flow stimulates smooth muscle cell hypertrophy and contractile protein expression

“…While this model system was not able to incorporate stretch, we previously examined its effect on SMCs. Our previous work showed that the nuclear shape, proliferation, and cytoskeletal structure of SMCs were influenced by varied cyclic stretch mechanical loading (50). Thus the addition of cyclic stretch to the high pulsatility flow system could further contribute to SMC hypertrophy and hyperplasia and should be studied in the future.…”

Altered phenotypic gene expression of 10T1/2 mesenchymal cells in nonuniformly stretched PEGDA hydrogels

“…Many studies have shown that cells of several types (including mesenchymal cells) tend to upregulate proliferation in the presence of stretch (5,13,15,46,49). Also, fibroblasts have been shown to proliferate more rapidly in uniaxial than biaxial stretch, supporting the graded response result found here (15).…”

Actuation means for the mechanical stimulation of living cells via microelectromechanical systems: A critical review

“…This concept can be scaled down to the microscale level, and MEMS devoted to the distention of cell substrates have been actuated by electrostatic actuators (Wu et al, 2005), fluids (Kim et al, 2007), and air pressure (Sim et al, 2007;Tan et al, 2008;Moraes et al, 2010).…”