Remodeling of Aligned Fibrous Extracellular Matrix by Encapsulated Cells Under Mechanical Stretching

Extracellular matrix remodeling is essential for the development and functions of connective tissues (e.g., heart, muscle and periodontal ligament), where ECM is generally with highly anisotropic features and under mechanical stimulation. However, the nature of how cells remodel their surrounding ECM under mechanical stimulation remains elusive. Herein, we encapsulated human periodontal ligament stem cells (hPDLSCs) within the aligned rat collagen scaffold labeled with fluorescein isothiocyanate (FITC) and provided continuous mechanical stimulation by magnetic stretching. Through tracking the FITC-labeled rat collagen scaffold and the newly secreted human type I collagen, we studied the mechanism of aligned ECM remodeling by encapsulated cells under mechanical stretching. We found that the aligned topography combined with magnetic stretching could significantly promote initial ECM degradation and new ECM secretion: the expression of matrix metalloproteinase 1 and 9 are significantly higher, and the elastic modulus increases from 50 kPa to 75 kPa as compared to the random collagen scaffold encapsulating hPDLSCs. Therefore, we decipher that cells remodel their surrounding ECM under continuous stretching through degradation and then secretion of new ECM to integrate with the aligned ECM and maintain tissue functions. Our study holds great potential in optimization of biomaterial scaffold design for clinical translation.