Cells in their in vivo microenvironment constantly encounter and respond to a multitude of signals. While the role of biochemical signals has long been appreciated, the importance of biophysical signals has only recently been investigated. Biophysical cues are presented in different forms including topography and mechanical stiffness imparted by the extracellular matrix and adjoining cells. Microfabrication technologies have allowed for the generation of biomaterials with microscale topographies to study the effect of biophysical cues on cellular function at the cell–substrate interface. Topographies of different geometries and with varying microscale dimensions have been used to better understand cell adhesion, migration, and differentiation at the cellular and sub-cellular scales. Furthermore, quantification of cell-generated forces has been illustrated with micropillar topographies to shed light on the process of mechanotransduction. In this review, we highlight recent advances made in these areas and how they have been utilized for neural, cardiac, and musculoskeletal tissue engineering application.

Micro- and nanotechnologies have emerged as potentially effective fabrication tools for addressing the challenges faced in tissue engineering and drug delivery. The ability to control and manipulate polymeric biomaterials on the micron and nanometer scale with these fabrication techniques has allowed for the creation of controlled cellular environments, engineering of functional tissues, and development of better drug delivery systems. In tissue engineering, micro- and nanotechnologies have enabled the recapitulating of the micro- and nanoscale detail of cell’s environment through controlling surface chemistry and topography of materials, generating 3D cellular scaffolds, and regulating cell-cell interactions. Furthermore, these technologies have led to advances in high-throughput screening (HTS), enabling rapid and efficient discovery of a library of materials and screening of drugs that induce cell-specific responses. In drug delivery, controlling the size and geometry of drug carriers with micro- and nanotechnologies have allowed for modulation of parameters such as bioavailability, pharmacodynamics, and cell-specific targeting. In this review, we introduce recent developments in micro- and nanoscale engineering of polymeric biomaterials with an emphasis on lithographic techniques, and present an overview of their applications in tissue engineering, HTS, and drug delivery.