Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds

Abstract

The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for 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 to 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 10-fold 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 minutes, 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.

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

“…However, this technique still requires extraction of residual (unpolymerized) monomer following gelation and, as a raster-based technique, is extremely slow for making anything but very small scaffolds. More promising is free-form printing techniques that can directly print a 3D gel structure in a single processing step using one of four approaches: (a) simple extrusion and deposition of preformed hydrogel tubes; [89] (b) printing and simultaneous rapid photocrosslinking of (meth)acrylated prepolymer solutions to convert the liquid-like prepolymer into a gel (also known as 3D printing stereolithography); [90] (c) printing a polyelectrolyte into a counterion solution (e.g., sodium alginate into a calcium ion bath) [91] to facilitate near-instantaneous ionotropic gelation; or (d) extrusion of thermoresponsive gelling pairs (e.g., sodium alginate/gelatin [92] ) on a cooled or heated support that induces gelation on contact. Stereolithography has been particularly commonly exploited in this context given its capacity for processing different polymers.…”

In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding

“…4,5 The technology presented in this paper is based on the principle of building 3D models, layer by layer, and enables the direct manufacturing of precise, complex-shaped implants using biocompatible or biodegradable materials from computerized data in several medical areas. [6][7][8][9] As a feasible, regenerative medicine approach, we developed completely autologous valved conduits, named Biovalves, [10][11][12] without any artificial scaffolds, through the use of "in-body tissue architecture" technology. This autologous Correspondence to: Y. Nakayama (e-mail: ny@ncvc.go.jp) Contract grant sponsor: Ministry of Education, Culture, Sports, Science, and Technology of Japan; contract grant number: B23360374 method is based on the phenomenon of tissue encapsulation of foreign materials implanted in living bodies.…”

Study of extrudability and standoff distance effect during nanoclay-enabled direct printing

“…in which various stimuli are used to induce rapid solidification of deposited build materials in situ, such as temperature change [14,15], ultraviolet (UV) radiation [16,17], and ionic cross-linking [10,18]. However, this fabrication methodology follows the traditional "solidification-while-printing" procedure and has some constraints including the requirement of rapid solidification of liquid build materials in order to retain the printed shape and nozzle clogging.…”