3D Bioprinting of a Living Aortic Valve

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
Native Aortic Valve
TE Aortic Valve
Mechanical 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

WF68DA
WF68DA/A2
WF68DA/A3
WF68DA/A4
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
IL-6 : proinflammatory cytokine, ↑ macrophage cytotoxic activity
MediVas TCT 04
Monocytes on PEAs secreted less IL-1β, a potent pro-inflammatory cytokine, that can increase the surface thrombogenicity of the endothelium, 24 hrs

3D Hydrogel Cytotoxicity Assay
96 well 3D gels with aortic valve interstitial cells

3D Cyotoxicity with Photo-Crosslinking
96 well 3D gels with aortic valve interstitial cells
90K cells/gel

Mechanical Testing of Hydrogels
Load Cell
Environmental Chamber
Hydrogel
Grips

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