Strategies for improving the physiological relevance of human engineered tissues

Abstract

This review examines important robust methods for sustained, steady-state, in vitro culture. To achieve 'physiologically relevant' tissues in vitro additional complexity must be introduced to provide suitable transport, cell signaling, and matrix support for cells in 3D environments to achieve stable readouts of tissue function. Most tissue engineering systems draw conclusions on tissue functions such as responses to toxins, nutrition, or drugs based on short-term outcomes with in vitro cultures (2-14 days). However, short-term cultures limit insight with physiological relevance because the cells and tissues have not reached a steady-state.

Keywords: 2D culture; 3D culture; bioreactors; long-term culture; microfluidics; tissue engineering.

Figure 1

To improve the 'physiological relevance' of engineered tissues biological context (extracellular matrix, vascularization and cell types), chemical cues, mechanical cues (bioreactors), spatial cues (culturing cells in 3D), and temporal timing of cultures should be considered.

Figure i

Long term culture in different in vitro platforms. To achieve greater culture duration in vitro; the increased complexity offered by 3D systems over 2D systems, along with larger tissue constructs with enhanced perfusion are required.