3D Printing Biomechanically Heterogeneous Tissue Engineered Aortic Valves
Laura A. Hockaday, Kevin H. Kang, Kevin Yeh, Nicholas W. Colagelo, Philip Y. Cheung, Jun Wu, Lawrence J. Bonassar, Hod Lipson, C C. Chu, Jonathan T. Butcher.
OBJECTIVE:Aortic valve disease is an increasing clinical problem for which prosthetic replacements remain poor options for younger patients. Tissue engineered living aortic valves have the potential for growth and remodeling, but current approaches have limited ability to mimic the native anatomical architecture. Current tissue engineering strategies do not adequately replicate key cellular and mechanical internal tissue heterogeneities within heart valves. To overcome these limitations, we combine microCT image processing, custom algorithms, and 3D printing to generate cell-seeded valve constructs incorporating complex geometry and anatomic heterogeneities.
METHODS:In this study, we used poly-(ethylene glycol) diacrylate (PEG-DA) hydrogels synthesized from 700 and 8000MW PEG-DA as model biomaterials. Aortic valve sterolithographic models were designed by scanning excised porcine aortic valves using microCT. Valve models were then printed using the hydrogels and a modified Fab@Home 3D printer. The printer rapidly deposited and photocrosslinked hydrogels simultaneously. Volumetric and layer-specific shape fidelity of printed valves were quantified using microCT. Porcine aortic valve interstitial cells (PAVICs) were cultured within printed valves. Heterogeneous aortic valve models were created from microCT scans using custom algorithms. Material gradients were then printed into the root wall, sinus wall, and leaflets.
RESULTS:A broad range of elastic responses were observed in uniaxial tensile and compressive mechanical tests when PEG-DA precursors of different MWs were blended. Modulus could be tuned between 75kPa and 5kPa, and the failure strain between 0.5 and 2. Different hydrogel blends were printed into valve constructs and gradients. Valve sizes from 12mm and 22mm inner diameter were printed. Valve constructs were printed in as little as 14 minutes. Shape accuracy was as high as 89%. PAVICs cultured on valve constructs were viable at 21 days. Heterogeneous printed valves exhibited controlled internal variation.
CONCLUSIONS:These results demonstrate that 3D tissue printing can fabricate anatomically precise, living valve conduits across the physiological size range. We were able to duplicate complex valve shape and control internal structure within valve constructs. This strategy has the potential to generate patient-specific valve replacements.
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