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3D Bioprinting of a Living Aortic Valve. Update : February 2, 2008. 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

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3d bioprinting of a living aortic valve

3D Bioprinting of a Living Aortic Valve

Update : February 2, 2008

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
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

Mechanical Properties

TE Aortic Valve

ideal biomaterial characteristics for engineered heart valves
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
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

WF68DA

WF68DA/A2

WF68DA/A4

WF68DA/A3

a pea is minimally immunogenic thrombogenic

Monocytes secreted over 5-fold less IL-6 on PEAs than on other polymers, 24 hrs

A-PEA is Minimally Immunogenic/Thrombogenic

IL-6 : proinflammatory cytokine, ↑ macrophage cytotoxic activity

Monocytes on PEAs secreted less IL-1β, a potent pro-inflammatory cytokine, that can increase the surface thrombogenicity of the endothelium, 24 hrs

MediVas TCT 04

3d hydrogel cytotoxicity assay
3D Hydrogel Cytotoxicity Assay

96 well 3D gels with aortic valve interstitial cells

3d cyotoxicity with photo crosslinking
3D Cyotoxicity with Photo-Crosslinking

96 well 3D gels with aortic valve interstitial cells

90K cells/gel

mechanical testing of hydrogels
Mechanical Testing of Hydrogels

Grips

Environmental Chamber

Hydrogel

Load Cell

high throughput measurement of photo crosslinking effects
High Throughput Measurement of Photo-Crosslinking Effects
  • Riboflavin induced crosslinking of collagen I
  • Central disk punched out via well guide
  • Dose dependent effects
next steps
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