Article: Hockaday LA, Kang KH, Colangelo NW, Cheung PYC, Duan B, Malone E, Wu J, Girardi LN, Bonassar LJ, Lipson H, Chu CC and Butcher JT (2012). “Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds.” Biofabrication 4(3).
Abstract: The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo engineered living tissue valve strategies. We present a novel simultaneous 3D printing/photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3 +/- 0.9 to 74.6 +/- 1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3 +/- 2.6, 85.1 +/- 2.0 and 73.3 +/- 5.2% for 22, 17 and 12 mm ID porcine valves; 89.1 +/- 4.0, 84.1 +/- 5.6 and 66.6 +/- 5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.