Spatial patterning of PCLµ-scaffolds directs 3D vascularized bio-constructs morphogenesisin vitro

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Modular tissue engineering (mTE) aims to create 3D tissue analogues in vitro.
• Integration with host vasculature is critical for engineered tissue survival in vivo.
• Current mTE strategies require improved control over vascularization.

Purpose of the Study:

• To develop a computer-aided modular approach for fabricating fully vascularized hybrid bio-constructs.
• To control micro-metric size and orientation of blood vessel growth.
• To investigate the role of micro-scaffold architecture on cell colonization and tissue formation.

Main Methods:

• Fabrication of polycaprolactone micro-scaffolds using fluidic emulsion technique.
• Creation of ordered and disordered micro-scaffold patterns via soft lithography.
• Co-culture of human dermal fibroblasts and endothelial cells on micro-scaffold patterns.
• Assembly of mono-layered bio-constructs into bi-layered, 1 mm thick constructs.

Main Results:

• The ordered micro-scaffold pattern provided superior control over bio-construct shape and vasculature architecture compared to the disordered pattern.
• Cell colonization and new tissue growth showed minor differences between ordered and disordered patterns.
• Fully vascularized, viable 1 mm thick bio-constructs were successfully created and cultured in vitro for 1 week.

Conclusions:

• Micro-scaffold architectural features and spatial patterning synergistically influence cell colonization and biosynthesis.
• The developed approach enables in silico design of vascular networks within modularly engineered bio-constructs.
• This work paves the way for advanced vascularized tissue engineering strategies.