3D Bioprinting of a Living Aortic Valve Jonathan Butcher (BME) C.C. Chu (DHE) Hod Lipson (MAE) Larry...
-
Upload
rose-strickland -
Category
Documents
-
view
217 -
download
0
Transcript of 3D Bioprinting of a Living Aortic Valve Jonathan Butcher (BME) C.C. Chu (DHE) Hod Lipson (MAE) Larry...
![Page 1: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/1.jpg)
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)
Update : February 2, 2008
![Page 2: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/2.jpg)
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
![Page 3: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/3.jpg)
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
![Page 4: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/4.jpg)
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
![Page 5: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/5.jpg)
A-PEA is Minimally Immunogenic/Thrombogenic
Monocytes secreted over 5-fold less IL-6 on PEAs than on other polymers, 24 hrs
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
![Page 6: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/6.jpg)
3D Hydrogel Cytotoxicity Assay96 well 3D gels with aortic valve interstitial cells
![Page 7: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/7.jpg)
3D Cyotoxicity with Photo-Crosslinking96 well 3D gels with aortic valve interstitial cells
90K cells/gel
![Page 8: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/8.jpg)
Mechanical Testing of Hydrogels
Load Cell
Environmental ChamberHydrogel
Grips
![Page 9: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/9.jpg)
High Throughput Measurement of Photo-Crosslinking Effects
• Riboflavin induced crosslinking of collagen I• Central disk punched out via well guide• Dose dependent effects
![Page 10: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/10.jpg)
3D Bioprinting Technology
![Page 11: 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) Update.](https://reader034.fdocuments.us/reader034/viewer/2022051315/56649e455503460f94b39fd3/html5/thumbnails/11.jpg)
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