Perfusion directed 3D mineral formation within cell-laden hydrogels

Area of Science:

• Biomaterials Engineering
• Tissue Engineering
• Regenerative Medicine

Background:

• Manufacturing large-scale bone tissue scaffolds faces challenges in nutrient perfusion through thick constructs.
• Advances in stem cell engineering and bioprinting offer potential but require solutions for construct vascularization.

Purpose of the Study:

• To develop a scalable method for creating thick, perfusable bone tissue constructs.
• To demonstrate the efficacy of using 3D printed sacrificial channels for nutrient delivery and bone mineralization.

Main Methods:

• Encapsulating osteoblast-like Saos-2 cells in gelatin methacrylate (GelMA) hydrogels.
• Utilizing 3D printed polyvinyl alcohol (PVA) pipes as sacrificial templates for perfusable channels.
• Employing a custom bioreactor for perfusing osteogenic media and quantifying mineral deposition via micro-CT.

Main Results:

• Progressive matrix mineralization was observed around perfused channels, unlike random deposition in static constructs.
• Micro-CT confirmed a direct relationship between channel perfusion time and construct mineralization.
• COMSOL modeling simulated oxygen diffusion, aiding the design of scaled-up constructs with 3D channel arrays.

Conclusions:

• The developed method provides a scalable approach for large-scale bone tissue scaffold fabrication.
• This technique utilizes readily available 3D printers, sacrificial materials, and hydrogels.
• The findings offer a model for creating functional bone tissue replacements through enhanced nutrient delivery.