Microscale approaches for molecular regulation of skeletal development

Abstract

Cells reside in dynamic, three-dimensional (3-D) microenvironments, which regulate their ability to respond to the spatiotemporal cues, such as neighbouring cells, the extracellular matrix, soluble factors and physical forces. Microscale technologies are rapidly emerging as key strategies to recapitulate the 3-D microarchitecture of the tissue, and the complex biochemical milieu and dynamic biomechanical cues of the in vivo cellular microenvironment. An overview of principal microscale approaches that have been successfully applied to promote skeletal development through augmentation of skeletal cell growth and differentiation is presented in this chapter. The microscale approaches include micropatterning techniques to fabricate defi ned microtopographies for directing skeletal cell differentiation; high-throughput material formulation and microarray techniques, in combination with microfabrication approaches, for rapid screening, selection and fabrication of 3-D biomaterial scaffolds with microscale resolution, which offers increased control of the cellular microenvironment and improved ability to direct skeletal stem cell fate; application of microbioreactors and microfl uidic scaffolds for culturing skeletal cells in closely regulated 3-D microenvironments that recapitulate the organ-specifi c microarchitecture and dynamic physical forces crucial for manipulation of long-term skeletal cell growth and differentiation; and microinjection/micromanipulation techniques for modulation of skeletal development in ex vivo models, followed by analyses of skeletal development and 3-D bone microarchitecture using microcomputed tomography. Thus, microscale technologies have enhanced our ability to generate physiologically relevant ex vivo microscale skeletal tissue models, which effectively recapitulate in vivo tissue development and function, and have the potential to be used for the development of skeletal disease models and for pharmacological and toxicological drug screening.