Additively Manufactured Multi-Morphology Bone-like Porous Scaffolds: Experiments and Micro-Computed Tomography-Finite Element Modeling Approaches

Tissue engineering, whose aim is to repair or replace damaged tissues by combining the principle of biomaterials and cell transplantation, is one of the most important and interdisciplinary fields of regenerative medicine. Despite remarkable progress, there are still some limitations in the tissue engineering field, among which designing and manufacturing suitable scaffolds. With the advent of additive manufacturing (AM), a breakthrough happened in the production of complex geometries. In this vein, AM has enhanced the field of bioprinting in generating biomimicking organs or artificial tissues possessing the required porous graded structure. In this study, triply periodic minimal surface structures, suitable to manufacture scaffolds mimicking bone’s heterogeneous nature, have been studied experimentally and numerically; the influence of the printing direction and printing material has been investigated. Various multi-morphology scaffolds, including gyroid, diamond, and I-WP, with different transitional zone, have been 3D printed and tested under compression; further, a micro-computed tomography (μCT) analysis has been employed to obtain the real geometry of printed scaffolds. Finite element analyses have been also performed and compared with experimental results. Finally, the scaffolds’ behavior under complex loading has been investigated based on the combination of μCT and finite element modeling

Modeling, assessment, and design of porous cells based on schwartz primitive surface for bone scaffolds

The design of bone scafolds for tissue regeneration is a topic of great interest, which involves diferent issues related to geometry of architectures, mechanical behavior, and biological requirements, whose optimal combination determines the success of an implant. Additive manufacturing (AM) has widened the capability to produce structures with complex geometries, which should potentially satisfy the diferent requirements. These architectures can be obtained by means of refned methods and have to be assessed in terms of geometrical and mechanical properties. In this paper a triply periodic minimal surface (TPMS), the Schwarz's Primitive surface (P-surface), has been considered as scafold unit cell and conveniently parameterized in order to investigate the efect of modulation of analytical parameters on the P-cell geometry and on its properties. Several are the cell properties, which can afect the scafold performance. Due to the important biofunctional role that the surface curvature plays in mechanisms of cellular proliferation and diferentiation, in this paper, in addition to properties considering the cell geometry in its whole (such as volume fraction or pore size), new properties were proposed. Tese properties involve, particularly, the evaluation of local geometrical-diferential properties of the P-surface. Te results of this P-cell comprehensive characterization are very useful for the design of customized bone scafolds able to satisfy both biological and mechanical requirements. A numerical structural evaluation, by means of fnite element method (FEM), was performed in order to assess the stifness of solid P-cells as a function of the changes of the analytical parameters of outer surface and the thickness of cell. Finally, the relationship between stifness and porosity has been analyzed, given the relevance that this property has for bone scafolds design

Relationship between the morphological, mechanical and permeability properties of porous bone scaffolds and the underlying microstructure

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold

Relationship between the morphological, mechanical and permeability properties of porous bone scaffolds and the underlying microstructure

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold

CAD-Based Porous Scaffold Design of Intervertebral Discs in Tissue Engineering

With the development and maturity of three-dimensional (3D) printing technology over the past decade, 3D printing has been widely investigated and applied in the field of tissue engineering to repair damaged tissues or organs, such as muscles, skin, and bones, Although a number of automated fabrication methods have been developed to create superior bio-scaffolds with specific surface properties and porosity, the major challenges still focus on how to fabricate 3D natural biodegradable scaffolds that have tailor properties such as intricate architecture, porosity, and interconnectivity in order to provide the needed structural integrity, strength, transport, and ideal microenvironment for cell- and tissue-growth. In this dissertation, a robust pipeline of fabricating bio-functional porous scaffolds of intervertebral discs based on different innovative porous design methodologies is illustrated. Firstly, a triply periodic minimal surface (TPMS) based parameterization method, which has overcome the integrity problem of traditional TPMS method, is presented in Chapter 3. Then, an implicit surface modeling (ISM) approach using tetrahedral implicit surface (TIS) is demonstrated and compared with the TPMS method in Chapter 4. In Chapter 5, we present an advanced porous design method with higher flexibility using anisotropic radial basis function (ARBF) and volumetric meshes. Based on all these advanced porous design methods, the 3D model of a bio-functional porous intervertebral disc scaffold can be easily designed and its physical model can also be manufactured through 3D printing. However, due to the unique shape of each intervertebral disc and the intricate topological relationship between the intervertebral discs and the spine, the accurate localization and segmentation of dysfunctional discs are regarded as another obstacle to fabricating porous 3D disc models. To that end, we discuss in Chapter 6 a segmentation technique of intervertebral discs from CT-scanned medical images by using deep convolutional neural networks. Additionally, some examples of applying different porous designs on the segmented intervertebral disc models are demonstrated in Chapter 6

Numerical and experimental evaluation of TPMS Gyroid scaffolds for bone tissue engineering

The combination of computational methods with 3D printing allows for the control of scaffolds microstructure. Lately, triply periodic minimal surfaces (TPMS) have been used to design porosity-controlled scaffolds for bone tissue engineering (TE). The goal of this work was to assess the mechanical properties of TPMS Gyroid structures with two porosity levels (50 and 70%). The scaffold stiffness function of porosity was determined by the asymptotic homogenisation method and confirmed by mechanical testing. Additionally, microCT analysis confirmed the quality of the printed parts. Thus, the potential of both design and manufacturing processes for bone TE applications is here demonstrated.info:eu-repo/semantics/publishedVersio

Three-Dimensional Printed Hydroxyapatite Bone Substitutes Designed by a Novel Periodic Minimal Surface Algorithm Are Highly Osteoconductive

Autologous bone remains the gold standard bone substitute in clinical practice. Therefore, the microarchitecture of newly developed synthetic bone substitutes, which reflects the spatial distribution of materials in the scaffold, aims to recapitulate the natural bone microarchitecture. However, the natural bone microarchitecture is optimized to obtain a mechanically stable, lightweight structure adapted to the biomechanical loading situation. In the context of synthetic bone substitutes, the application of a Triply Periodic Minimum Surface (TPMS) algorithm can yield stable lightweight microarchitectures that, despite their demanding architectural complexity, can be produced by additive manufacturing. In this study, we applied the TPMS derivative Adaptive Density Minimal Surfaces (ADMS) algorithm to produce scaffolds from hydroxyapatite (HA) using a lithography-based layer-by-layer methodology and compared them with an established highly osteoconductive lattice microarchitecture. We characterized them for compression strength, osteoconductivity, and bone regeneration. The in vivo results, based on a rabbit calvaria defect model, showed that bony ingrowth into ADMS constructs as a measure of osteoconduction depended on minimal constriction as it limited the maximum apparent pore diameter in these scaffolds to 1.53 mm. Osteoconduction decreased significantly at a diameter of 1.76 mm. The most suitable ADMS microarchitecture was as osteoconductive as a highly osteoconductive orthogonal lattice microarchitecture in noncritical- and critical-size calvarial defects. However, the compression strength and microarchitectural integrity in vivo were significantly higher for scaffolds with their microarchitecture based on the ADMS algorithm when compared with high-connectivity lattice microarchitectures. Therefore, bone substitutes with high osteoconductivity can be designed with the advantages of the ADMS-based microarchitectures. As TPMS and ADMS microarchitectures are true lightweight structures optimized for high mechanical stability with a minimal amount of material, such microarchitectures appear most suitable for bone substitutes used in clinical settings to treat bone defects in weight-bearing and non-weight-bearing sites

Ti-6Al-4V triply periodic minimal surface structures for bone implants fabricated via selective laser melting

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tTriply periodic minimal surface (TPMS) structures have already been shown to be a versatile source of biomorphic scaffold designs. Therefore, in this work, Ti-6Al-4V Gyroid and Diamond TPMS lattices having an interconnected high porosity of 80-95% and pore sizes in the range of 560-1600 μm and 480-1450 μm respectively were manufactured by selective laser melting (SLM) for bone implants. The manufacturability, microstructure and mechanical properties of the Ti-6Al-4V TPMS lattices were evaluated. Comparison between 3D micro-CT reconstructed models and original CAD models of the Ti-6Al-4V TPMS lattices shows excellent reproduction of the designs. The as-built Ti-6Al-4V struts exhibit the microstructure of columnar grains filled with very fine and orthogonally oriented α' martensitic laths with the width of 100-300 nm and have the microhardness of 4.01 ± 0.34 GPa. After heat treatment at 680°C for 4h, the α' martensite was converted to a mixture of α and β, in which the α phase being the dominant fraction is present as fine laths with the width of 500-800 nm and separated by a small amount of narrow, interphase regions of dark β phase. Also, the microhardness is decreased to 3.71 ± 0.35 GPa due to the coarsening of the microstructure. The 80-95% porosity TPMS lattices exhibit a comparable porosity with trabecular bone, and the modulus is in the range of 0.12-1.25 GPa and thus can be adjusted to the modulus of trabecular bone. At the same range of porosity of 5-10%, the moduli of cortical bone and of the Ti-6Al-4V TPMS lattices are in a similar range. Therefore, the modulus and porosity of Ti-6Al-4V TPMS lattices can be tailored to the levels of human bones and thus reduce or avoid "stress shielding" and increase longevity of implants. Due to the biomorphic designs, and high interconnected porosity and stiffness comparable to human bones, SLM-made Ti-6Al-4V TPMS lattices can be a promising material for load bearing bone implants.This work is supported by the UK Technology Strategy Board (TSB) funded project(TP14/BA036D) entitled “SAVING – Sustainable product development via design optimisation and AdditiVe manufacturing”, National Natural Science Foundation of China (Grant no. 51375188 and 51375189) and the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2013C071)

Numerical-experimental analysis of the permeability-porosity relationship in triply periodic minimal surfaces scaffolds

Bone Tissue Engineering has been focusing on improving the current methods for bone repair, being the use of scaffolds presented as an upgrade to traditional surgery techniques. Scaffolds are artificially porous matrices, meant to promote cell seeding and proliferation, being these properties influenced by the permeability of the structure. This work employed experimental pressure drop tests and Computational Fluid Dynamics models to assess permeability (and fluid streamlines) within different triply periodic minimal surfaces scaffold geometries (Schwarz D, Gyroid and Schwarz P). The pressure outputs from the computational analysis presented a good correlation with the experimental results, with R2 equal to 0.903; they have also shown that a lower porosity may not mean a lower permeability if the geometry is altered, such as the difference between 60% porous Gyroid scaffolds (8.1*10-9 mm2) and 70% porous Schwarz D scaffolds (7.1*10-9 mm2). Fluid streamlines revealed how the Gyroid geometries are the most appropriate design for most bone tissue engineering applications, due to their consistent fluid permeation, followed by Schwarz D. The Schwarz P geometries have shown flat streamlines and significant variation of the permeability with the porosity (an increase of 10% in their porosity lead to an increase in the permeability from 5.1*10-9 mm2 to 11.7*10-9 mm2), which would imply a poor environment for cell seeding and proliferation.info:eu-repo/semantics/publishedVersio