Advances in techniques for probing mechanoregulation of tissue morphogenesis

Cells process various mechanical cues in the microenvironment to self-organize into high-order architectures during tissue morphogenesis. Impairment of morphogenic processes is the underlying cause of many diseases; as such, understanding the regulatory mechanisms associated with these processes will form the foundation for the development of innovative approaches in cell therapy and tissue engineering. Nevertheless, little is known about how cells collectively respond to mechanical cues in the microenvironment, such as global geometric guidance, local cell-cell interactions, and other physicochemical factors, for the emergence of the structural hierarchy across multiple length scales. To elucidate the mechanoregulation of tissue morphogenesis, numerous approaches based on biochemical, biomaterial, and biophysical techniques have been developed in the past decades. In this review, we summarize techniques and approaches for probing the mechanoregulation of tissue morphogenesis and illustrate their applications in vasculature development. The potential and limitations of these methods are also discussed with a view toward the investigation of a wide spectrum of tissue morphogenic processes.