Mimicking the Dynamic Mechanical ECM Using Engineered Biomaterials to Investigate Cellular Crosstalk ^†

1. Introduction

The stiffness of a tissue changes during the lifetime of an individual and is an indicator of age, disease, and pathophysiological conditions. Increased tissue stiffness is a hallmark of illnesses like cancer and cardiovascular diseases, causing major mortality worldwide. Cells interact with the mechanical cues of the surrounding ECM by adjusting themselves through communication from the nanometer to the meter scale by rearranging their cytoskeleton, nuclear envelope structure and composition, and migration. Understanding how forces work will unlock new avenues in disease research, regenerative medicine, and the design of implantable biomaterials.

2. Materials and Methods

A 3D silk fibroin biomaterial library is created with diverse mechanical stiffness ranging from ~3 kPa to 0.4 kPa.

3. Results

The cell–cell and cell–ECM interactions in this dynamic niche are evaluated using stem cells. The up- or down-regulation of certain genes with ECM stiffness acts as a marker of cellular response to dynamic mechanical ECM, while cell-mediated mineralization is indicative of cell–cell and cell–ECM crosstalk.

4. Conclusions

This study also confirms that biomimetic, dynamic ECM-mediated physical cues not only influence the differentiation behavior of the cells but also regulate the migration of surrounding cells toward the engineered niche. However, further investigation is needed.