Dynamic Modulation of the Microenvironment Promotes Functional Maturation of Engineered Tissues

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cell Biology

Background:

• In vivo cellular microenvironments are complex, involving interactions between cells and the extracellular matrix.
• Engineered tissues often lack this complexity, limiting their ability to accurately mimic native tissue dynamics in vitro.

Purpose of the Study:

• To develop a method for dynamically modulating the cellular microenvironment in engineered tissues during maturation.
• To assess the impact of dynamic microenvironment control on the development of vascular and cardiac tissues, as well as stem cell differentiation.

Main Methods:

• Utilized a biocompatible small molecule capable of diffusing into maturing tissues to dynamically alter the cellular microenvironment.
• Administered the small molecule in multiple doses at different maturation stages to achieve controlled adjustments.
• Cultured endothelial cells, engineered cardiac tissues, and induced pluripotent stem cells within dynamically modulated hydrogel matrices.

Main Results:

• Dynamically modulated endothelial cell cultures formed thicker, more native-like blood vessels compared to traditional methods.
• Engineered cardiac tissues exhibited enhanced contraction strength and more mature electrophysiology in dynamic matrices.
• Coordinating matrix stiffness with stem cell developmental stages during differentiation maximized cardiomyocyte functionality.

Conclusions:

• Dynamic modulation of the tissue microenvironment using a diffusible small molecule offers a facile and safe approach to improve engineered tissue development.
• This technology represents a significant advancement toward more accurate in vitro recapitulation of complex biological processes for tissue engineering applications.