AR3T supports the development and testing of ex vivo systems capable of applying biologically-relevant mechanical load regimens to an array of microtissue constructs in order to examine the effects of mechanical forces on stem cells.
Tissue loading is a powerful means for modulating the tissue microenvironment and promoting healing. However, not all loading is the same, and both cellular and tissue responses are highly sensitive to characteristics such as stiffness, magnitude, frequency and duration of the stimulus. Indeed, stem cells interpret mechanical forces in a broad spectrum of ways that can affect their viability, phenotype, secretory properties and other functions.
Significant effort has focused on the engineering of microscale tissue constructs, often derived from or comprised entirely of different types of stem cells, for the purpose of modeling 3D cell assemblies ex vivo, for example. Tissue constructs have been developed using microfabricated technologies or directly within microfabricated devices in order to create arrays of microscale tissues for high-throughput applications such as drug screening. Despite technical advances allowing the creation of complex, well-defined environmental conditions, most currently available technologies are not capable of applying mechanical loading regimens that can replicate biological forces experienced by stem cells, particularly in dynamic multicellular physical environments. Current approaches to applying mechanical forces on the microscale to engineered tissues typically rely on suspending cells at relatively low density in a hydrogel material and/or physically attaching constructs to deformable substrates or post/pillars. Dynamic microfabricated systems have been developed, such as with pneumatically-actuated microposts, to apply a range of different forces to microtissue constructs in parallel. By varying the dimensions of the actuation diaphragms, it is possible to obtain a range of vertical displacements with a single pressure across an entire array of constructs. While such systems enable well-controlled applications of mechanical forces and measurements, most do not accurately mimic the multicellular physical composition of native tissues and, thus, the direct translational knowledge gained by the results of such experiments may be limited.
AR3T provides technology development grants to support the development and validation of technologies that will be used for the ex vivo elucidation of the stem cell response to extrinsic mechanical signals to simulate conditions analogous to rehabilitation.
One example of an AR3T-funded project: the development and testing of an ex vivo system capable of examining the effect of mechanical forces on stem cells in a 3D multicellular environment that allows for both static and cyclic mechanical loading of the microtissue constructs using different durations and frequencies of time.