Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications

The development of biomedical devices and reconstruction of functional ex vivo tissues often requires the need to fabricate biomimetic surfaces with features of sub-micrometer precision. This can be achieved with the advancements in micro-/nano-engineering techniques, allowing researchers to manipulate a plethora of cellular behaviors at the cell-biomaterial interface. Systematic studies conducted on these 2D engineered surfaces have unraveled numerous novel findings that can potentially be integrated as part of the design consideration for future 2D and 3D biomaterials and will no doubt greatly benefit tissue engineering. In this review, recent developments detailing the use of micro-/nano-engineering techniques to direct cellular orientation and function pertinent to soft tissue engineering will be highlighted. Particularly, this article aims to provide valuable insights into distinctive cell interactions and reactions to controlled surfaces, which can be exploited to understand the mechanisms of cell growth on micro-/nano-engineered interfaces, and to harness this knowledge to optimize the performance of 3D artificial soft tissue grafts and biomedical applications. Advanced micro-/nanofabrication techniques applied at the cell-biomaterial interface can modulate a wide range of cellular activities such as i) spreading and adhesion, ii) induced alignment, and iii) stem cell differentiation. These 2D engineered surfaces and observations can be translated to the fabrication of 3D constructs with precise control over spatiotemporal regulatory factors.