Scaffold Architecture and Matrix Strain Modulate Mesenchymal Cell and Microvascular Growth and Development in a Time...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Volumetric tissue engineering relies on vascular networks, influenced by scaffold properties.
• Scaffold pore size and mechanical properties affect cell behavior and tissue development.
• Scaffold architecture may control stromal-vessel interactions during tissue morphogenesis.

Purpose of the Study:

• To investigate the impact of scaffold pore architecture on stromal-vessel interactions.
• To assess the role of pore size in vascularization within engineered tissue constructs.
• To correlate computational models with experimental findings on vascular network formation.

Main Methods:

• Mesenchymal stem cells (MSCs) and microvascular fragments (MVFs) were cultured in hydroxyapatite scaffolds with varying pore sizes (450, 340, 250 μm) and fibrin hydrogels.
• In vitro assessment over 21 days, including mRNA sequencing.
• Development of a computational mechanics model to predict vascularization based on scaffold architecture and matrix stiffness.

Main Results:

• Vessel growth, branching, and network formation were observed in scaffolds, with greater branching in larger pores.
• Hypoxia and angiogenic signaling (VEGF, BMP2) stimulated vessel growth within scaffolds.
• Computational models accurately predicted experimental trends in vascularization and branching morphology.

Conclusions:

• Scaffold architecture significantly influences microvessel growth and branching morphology.
• Hypoxia signaling and mechanotransduction within the scaffold matrix are key drivers of cell and vessel development.
• Computational modeling provides a valuable tool for predicting vascularization in tissue-engineered constructs.