3D Bioprinting of a Living Aortic Valve
Jonathan Butcher (BME)
C.C. Chu (DHE)
Hod Lipson (MAE)
Larry Bonassar (MAE/BME)
Len Girardi (Weill Medical)
Clinical Need and State of the Art
Nearly 100,000 valve replacements annually in US
Prosthetic valves poor choice for young/active
Tissue engineering has potential but limited by inability to mimic 3D anatomy and heterogeneous material properties
Ideal Biomaterial Characteristics for Engineered Heart Valves
Enzymatically bioadsorbable
Cell mediated, non-toxic end products
Aqueous based hydrogel
Can fabricate with cells distributed within matrix
Non-thrombogenic/non-immunogenic
Tunable material properties: crosslinking
Bio-functionality
Charge, hydrophobicity, hydroxyl/amine groups
Arginine Based PEA Hydrogels (A-PEA)
Precursors are water soluble
Can be photo-crosslinked by UV light
Degraded by a variety of cellular enzymes
Numerous accessible functional groups
A-PEA is Minimally Immunogenic/Thrombogenic
3D Hydrogel Cytotoxicity Assay
3D Cyotoxicity with Photo-Crosslinking
Mechanical Testing of Hydrogels
High Throughput Measurement of Photo-Crosslinking Effects
Riboflavin induced crosslinking of collagen I
Central disk punched out via well guide
Dose dependent effects
3D Bioprinting Technology
Next Steps
Switch to A-PEA based hydrogels
Cytotoxicity of crosslinking dose
Mechanical testing of crosslinking effects
Incorporate a second syringe in the printer
Print a temporary scaffold to support structure
Print 3D anatomical models of heart valves
Axisymmetric aortic valve geometry
Anatomical models via MRI: Yi Wang, Weill Med
Incorporate a tuned UV laser to the print head
Spot specific engineered tissue material properties