Design and Fabrication of 3D Printed Tissue Scaffolds Informed by Mechanics and Fluids Simulations

2017 ◽  
Author(s):  
Paul F. Egan ◽  
Veronica C. Gonella ◽  
Max Engensperger ◽  
Stephen J. Ferguson ◽  
Kristina Shea
Keyword(s):  
Elastic Modulus ◽  
Additive Manufacturing ◽  
Shear Modulus ◽  
Pore Size ◽  
Design Automation ◽  
Volume Ratio ◽  
Tissue Growth ◽  
Tissue Scaffolds ◽  
Trade Offs ◽  
3D Printed

Advances in additive manufacturing are enabling the fabrication of lattices with complex geometries that are potentially advantageous as tissue scaffolds. Scaffold design for optimized mechanics and tissue growth is challenging, due to complicated trade-offs among scaffold structural properties including porosity, pore size, surface-volume ratio, elastic modulus, shear modulus, and permeability. Here, a design for additive manufacturing approach is developed for tuning unit cell libraries as tissue scaffolds through (1) simulation, (2) design automation, and (3) fabrication. Finite element simulations are used to determine elastic and shear moduli of lattices as a function of porosity. Fluids simulations suggest that lattice permeability scales with porosity cubed over surface-volume ratio squared. The design automation approach uses simulation results to configure lattices with specified porosity and pore size. A cubic and octet lattice are fabricated with pore sizes of 1,000μm and porosities of 60%; these lattice types represent unit cells with high unidirectional elastic modulus/permeability and high shear modulus/surface-volume ratio, respectively. Imaging suggests the 3D printing process recreates the form accurately, but distorts microscale features. Future iterations are required to determine how lattices perform in comparison to computational predictions. The developed approach provides the foundations of a design automation approach for optimized 3D printed tissue scaffolds informed by simulation and experiments.

Design and Biological Simulation of 3D Printed Lattices for Biomedical Applications

2019 ◽  
Author(s):  
Paul F. Egan
Keyword(s):  
Sensitivity Analysis ◽  
Biomedical Applications ◽  
Volume Ratio ◽  
Computational Design ◽  
Tissue Growth ◽  
Analytical Relationship ◽  
Biological Growth ◽  
Trade Offs ◽  
Unit Cells ◽  
3D Printed

Abstract There is great potential for using 3D printed designs fabricated via additive manufacturing processes for diverse biomedical applications. 3D printing offers capabilities for customizing designs for each new fabrication that could leverage automated design processes for personalized patient care, but there are challenges in developing accurate and efficient assessment methods. Here, we conduct a sensitivity analysis for a biological growth simulation for evaluating 3D printed lattices for regenerating bone and then use these simulations to identify performance trends. Four design topologies were compared by generating varied unit cells. Biological growth was modeled in a voxel environment by simulating the advancement of a tissue front by calculating its local curvature. Designs were generated with properties suitable for bone tissue engineering, namely 50% porosity and microscale pores. The sensitivity analysis determined trade-offs between prediction consistency and computation time, suggesting calculating curvature within a radius of 7.5 voxels is sufficient for most cases. Topologies were compared in bulk with design variations. All topologies had similar tissue growth rates for a given surface-volume ratio, but with differing unit cell sizes. These findings inform future optimization for selecting unit cells based on volume requirements and other criteria, such as mechanical stiffness. A fitted analytical relationship predicted tissue growth rate based on a design’s surface-volume ratio, which enables design evaluation without computationally expensive simulations. Lattices were 3D printed with biocompatible materials as proof-of-concepts, demonstrating the feasibility of the approach for future computational design methods for personalized medicine.

Computational Investigation of Tissue and Blood Vessel Growth Trade-Offs in Hierarchical Lattices

2021 ◽  
Author(s):  
Amit M. E. Arefin ◽  
Paul F. Egan
Keyword(s):  
Blood Vessel ◽  
Computational Design ◽  
Tissue Growth ◽  
Beam Diameter ◽  
Design Decisions ◽  
Large Void ◽  
Biomechanical Behavior ◽  
Trade Offs ◽  
Vessel Growth ◽  
3D Printed

Abstract Computational design is growing in necessity for advancing biomedical technologies, particularly when considering complex systems with numerous trade-offs among design decisions and resulting biomechanical behavior. In tissue engineering applications, porous bone scaffold structures enabled by 3D printing can have intricate lattice structures and hierarchical features that mimic the biological hierarchy of natural bone. However, these hierarchies create challenges in predicting the tissue regeneration process and how different scales of the hierarchy drive varied biological behaviors. Smaller pores facilitate tissue growth while larger pores are necessary for blood vessel growth, however, identifying favorable trade-offs to maximize growth of both tissue and blood vessels remains a challenge, especially for complex 3D printed structures. Here, we adapt tissue and blood vessel growth models for predicting biological growth in scaffolds with varied combinations of beam diameter size, unit cell topology, and hierarchical pore size/distribution. Findings demonstrate that on a normalized scale lattices with no large voids provide greater tissue growth but less blood vessel growth in comparison to lattice layouts with large void areas. A lattice with large void channels provided the greatest blood vessel growth but poorer tissue growth, while a lattice with evenly distributed large voids provided a better compromise between the two types of growth. Overall, these findings demonstrate the merit in computational investigations for design trade-off comparisons in tissue scaffolds, and provide a foundation for future explorations of biological design decisions for regenerative medicine and 3D printed systems.

scholarly journals Influence of Crosslinking on the Mechanical Behavior of 3D Printed Alginate Scaffolds: Experimental and Numerical Approaches

2018 ◽  
Author(s):  
Saman Naghieh ◽  
Mohammad Reza Karamooz-Ravari ◽  
Md Sarker ◽  
Eva Karki ◽  
Xiongbiao Chen
Keyword(s):  
Mechanical Properties ◽  
Elastic Modulus ◽  
Mechanical Behavior ◽  
Three Dimensional ◽  
Decisive Role ◽  
Element Model ◽  
Tissue Scaffolds ◽  
3D Bioprinting ◽  
3D Printed ◽  
Numerical Approaches

Tissue scaffolds fabricated by three-dimensional (3D) bioprinting are attracting considerableattention for tissue engineering applications. Because the mechanical properties of hydrogelscaffolds should match the damaged tissue, changing various parameters during 3D bioprintinghas been studied to manipulate the mechanical behavior of the resulting scaffolds. Crosslinkingscaffolds using a cation solution (such as CaCl2) is also important for regulating the mechanicalproperties, but has not been well documented in the literature. Here, the effect of variedcrosslinking agent volume and crosslinking time on the mechanical behavior of 3D bioplottedalginate scaffolds was evaulated using both experimental and numerical methods. Compressiontests were used to measure the elastic modulus of each scaffold, then a finite element model wasdeveloped and a power model used to predict scaffold mechanical behavior. Results showed thatcrosslinking time and volume of crosslinker both play a decisive role in modulating the mechanicalproperties of 3D bioplotted scaffolds. Because mechanical properties of scaffolds can affect cellresponse, the findings of this study can be implemented to modulate the elastic modulus ofscaffolds according to the intended application.

scholarly journals Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

2020 ◽  
Author(s):  
Pascal R. Buenzli ◽  
Matthew Lanaro ◽  
Cynthia S. Wong ◽  
Maximilian P. McLaughlin ◽  
Mark C. Allenby ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pore Size ◽  
Reaction Diffusion ◽  
Tissue Growth ◽  
Simple Reaction ◽  
Cell Proliferation And Migration ◽  
Reaction Diffusion Model ◽  
3D Printed ◽  
And Migration ◽  
Proliferation And Migration

AbstractTissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction–diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction–diffusion models of cells that have robust, consistent behaviours.

scholarly journals Integrated Design Approaches for 3D Printed Tissue Scaffolds: Review and Outlook

Materials ◽  
2019 ◽  
Vol 12 (15) ◽  
pp. 2355 ◽  
Author(s):  
Egan
Keyword(s):  
3D Printing ◽  
Material Selection ◽  
Integrated Design ◽  
Simulation Models ◽  
Tissue Scaffolds ◽  
Mechanical Stiffness ◽  
Tissue Scaffold ◽  
Trade Offs ◽  
3D Printed ◽  
New Research

Emerging 3D printing technologies are enabling the fabrication of complex scaffold structures for diverse medical applications. 3D printing allows controlled material placement for configuring porous tissue scaffolds with tailored properties for desired mechanical stiffness, nutrient transport, and biological growth. However, tuning tissue scaffold functionality requires navigation of a complex design space with numerous trade-offs that require multidisciplinary assessment. Integrated design approaches that encourage iteration and consideration of diverse processes including design configuration, material selection, and simulation models provide a basis for improving design performance. In this review, recent advances in design, fabrication, and assessment of 3D printed tissue scaffolds are investigated with a focus on bone tissue engineering. Bone healing and fusion are examples that demonstrate the needs of integrated design approaches in leveraging new materials and 3D printing processes for specified clinical applications. Current challenges for integrated design are outlined and emphasize directions where new research may lead to significant improvements in personalized medicine and emerging areas in healthcare.

AM-Serienproduktion für die Automobilindustrie/AM series production for the automotive industry

2020 ◽  
Vol 110 (11-12) ◽  
pp. 752-757
Author(s):  
Lukas Weiser ◽  
Marco Batschkowski ◽  
Niclas Eschner ◽  
Benjamin Häfner ◽  
Ingo Neubauer ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Automotive Industry ◽  
Series Production ◽  
Production Scale ◽  
Additive Fertigung ◽  
Small Series ◽  
Start Up ◽  
3D Printed ◽  
Component Quality

Die additive Fertigung schafft neue Gestaltungsfreiheiten. Im Rahmen des Prototypenbaus und der Kleinserienproduktion kann das Verfahren des selektiven Laserschmelzens genutzt werden. Die Verwendung in der Serienproduktion ist bisher aufgrund unzureichender Bauteilqualität, langen Anlaufzeiten sowie mangelnder Automatisierung nicht im wirtschaftlichen Rahmen möglich. Das Projekt „ReAddi“ möchte eine erste prototypische Serienfertigung entwickeln, mit der additiv gefertigte Bauteile für die Automobilindustrie wirtschaftlich produziert werden können. Additive manufacturing (AM) offers new freedom of design. The selective laser-powderbed fusion (L-PBF) process can be used for prototyping and small series production. So far, it has not been economical to use it on a production scale due to insufficient component quality, long start-up times and a lack of automation. The project ReAddi aims to develop a first prototype series production to cost-effectively manufacture 3D-printed components for the automotive industry.

Fused Filament Fabrication 3D Printed Polylactic Acid Electroosmotic Pumps

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Liang Wu ◽  
Stephen Beirne ◽  
Joan-Marc Cabot Canyelles ◽  
Brett Paull ◽  
Gordon G. Wallace ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
3D Printing ◽  
Polylactic Acid ◽  
Fused Filament Fabrication ◽  
Flexible Approach ◽  
Electroosmotic Pump ◽  
3D Printed ◽  
Electroosmotic Pumps

Additive manufacturing (3D printing) offers a flexible approach for the production of bespoke microfluidic structures such as the electroosmotic pump. Here a readily accessible fused filament fabrication (FFF) 3D printing...

scholarly journals Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2146
Author(s):  
Jian Guan ◽  
Fu-zhen Yuan ◽  
Zi-mu Mao ◽  
Hai-lin Zhu ◽  
Lin Lin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Elastic Modulus ◽  
Chondrogenic Differentiation ◽  
Marker Genes ◽  
Self Healing ◽  
Polyethylene Glycol Diacrylate ◽  
3D Microenvironment ◽  
3D Printed

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

scholarly journals Shear modulus and yield stress of foams: contribution of interfacial elasticity

Soft Matter ◽  
2021 ◽  
Vol 17 (14) ◽  
pp. 3937-3944
Author(s):  
Annika R. Völp ◽  
Norbert Willenbacher
Keyword(s):  
Elastic Modulus ◽  
Block Copolymer ◽  
Shear Modulus ◽  
Yield Stress ◽  
Protein Food ◽  
General Correlation

A general correlation of foam shear modulus G0 and yield stress τy with the interfacial elastic modulus of foaming solutions in shear and dilation E∞ was found for surfactant, block-copolymer, protein, food, and particle-stabilized foams.

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