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.
A major challenge in tissue engineering is the generation of cell-seeded implants with structures that mimic native tissue, both in anatomic geometries and intratissue cell distributions. By combining the strengths of injection molding tissue engineering with those of solid freeform fabrication (SFF), three-dimensional (3-D) pre-seeded implants were fabricated without custom-tooling, enabling efficient production of patient-specific implants. The incorporation of SFF technology also enabled the fabrication of geometrically complex, multiple-material implants with spatially heterogeneous properties that would otherwise be challenging to produce. Utilizing a custom-built robotic SFF platform and gel deposition tools, alginate hydrogel was used with calcium sulfate as a crosslinking agent to produce pre-seeded living implants of arbitrary geometries. The process was determined to be sterile and viable at 94 +/- 5%. The GAG and hydroxyproline production was found to be similar to that of other implants fabricated using the same materials with different shaping methods. The geometric fidelity of the process was quantified by using the printing platform as a computerized measurement machine (CMM); the RMS surface roughness of printed samples in the z-dimension was found to be 0.16 +/- 0.02 mm.
Solid freeform fabrication has the potential to revolutionize manufacturing, perhaps even to allow consumers to customize and manufacture goods cost-effectively in their own home. At present, the florescence of the technology is limited by a "chicken and egg" paradox. There is insufficient consumer demand and too narrow a range of applications for SFF systems to allow mass production to reduce their cost and complexity. At the same time, consumer applications for, demand for, and indeed awareness of SFF technology is limited by its high cost and complexity. We posit that just as the personal computer revolution was spurred by development of computer kits, getting SFF technology into the hands of hobbyists and hackers will simultaneously generate applications for, and improvements to it. To this end, we have developed the Fab@Home personal SFF kit, and are developing a user-group website to promote exchange of ideas and improvements. The designs and software for Fab@Home will be freely distributed, and constructing a first generation kit should cost roughly $2000. The kit design and a working unit will be presented, along with our experience deploying a unit for public use.
Purpose-To seek to produce low-voltage, soft mechanical actuators entirely via freeform fabrication as part of a larger effort to freeform fabricate complete electromechanical devices with lifelike and/or biocompatible geometry and function. Design/methodology/approach-The authors selected ionomeric polymer-metal composite (IPMC) actuators from the literature and the authors' own preliminary experiments as most promising for freeform fabrication. The authors performed material formulation and manual device fabrication experiments to arrive at materials which are amenable to robotic deposition and developed an SFF process which allows the production of complete IPMC actuators and their fabrication substrate integrated within other freeform fabricated devices. The authors freeform fabricated simple IPMC's, explored some materials/performance interactions, and preliminarily characterized these devices in comparison to devices produced by non-SFF methods. Findings-Freeform fabricated IPMC actuators operate continuously in air for more than 4 h and 3,000 bidirectional actuation cycles. The output stress scaled to input power is one to two orders of magnitude inferior to that of non-SFF devices. Much of this difference may be associated with processsensitive microstructure of materials. Future work will investigate this performance gap. Research limitations/implications-Device performance is sufficient to continue exploration of SFF of complete electromechanical devices, but will need improvement for broader application. The feasibility of the approach for producing devices with complex, non-planar geometry has not been demonstrated. Practical implications-This work demonstrates the feasibility of freeform fabricating IPMC devices, and lays groundwork for further development of the materials and methods. Originality/value-This work constitutes the first demonstration of complete, functional, IPMC actuators produced entirely by freeform fabrication.
Quantification of shape fidelity of complex geometries for tissue-engineered constructs has not been thoroughly investigated. The objective of this study was to quantitatively describe geometric fidelities of various approaches to the fabrication of anatomically shaped meniscal constructs. Ovine menisci (n ¼ 4) were imaged using magnetic resonance imaging (MRI) and microcomputed tomography (mCT). Acrylonitrile butadiene styrene plastic molds were designed from each imaging modality and three-dimensional printed on a Stratasys FDM 3000. Silastic impression molds were fabricated directly from ovine menisci. These molds were used to generate shaped constructs using 2% alginate with 2% CaSO 4 . Solid freeform fabrication was conducted on a custom openarchitecture three-dimensional printing platform. Printed samples were made using 2% alginate with 0.75% CaSO 4 . Hydrogel constructs were scanned via laser triangulation distance sensor. The point cloud images were analyzed to acquire computational measurements for key points of interest (e.g., height, width, and volume). Silastic molds were within AE10% error with respect to the native tissue for seven key measurements, mCT molds for six of seven, mCT prints for four of seven, MRI molds for five of seven, and MRI prints for four of seven. This work shows the ability to generate and quantify anatomically shaped meniscal constructs of high geometric fidelity and lends insight into the relative geometric fidelities of several tissue engineering techniques.
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