Engineering fibronectin-templated multi-component fibrillar extracellular matrices to modulate tissue-specific cell...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cell Biology

Background:

• Cells construct fibrillar extracellular matrix (ECM) scaffolds using fibronectin (FN) and other proteins, crucial for tissue-specific environments.
• Existing methods for bioengineering 3D FN matrices in vitro do not fully capture the complexity of native ECM compositions and cellular responses.

Purpose of the Study:

• To engineer novel 3D fibrillar matrices templated by fibronectin that can incorporate other ECM proteins, such as vitronectin, collagen, and laminin.
• To create biomimetic ECM architectures that recapitulate in vivo tissue-specific compositions and guide cellular behavior.

Main Methods:

• Utilized innate fibrillogenic mechanisms of ECM proteins (shear forces, pH-dependent interactions, binding domains) for co-assembly.
• Engineered large-scale, multi-composite 3D fibrillar ECM matrices with tailored compositions and morphologies.

Main Results:

• Successfully recapitulated diverse tissue-specific ECM compositions and morphologies.
• Demonstrated the ability of engineered matrices to guide fibroblast adhesion, 3D fibroblast tissue formation, and epithelial cell morphogenesis.
• Showcased customized matrices supporting neuronal network growth and human brain organoid development.

Conclusions:

• Developed a versatile platform for engineering complex, multi-composite 3D fibrillar ECM matrices.
• These engineered matrices can modulate tissue-specific cellular responses and advance studies in cell biology and regenerative medicine.