Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: A review.

Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

Organ Printing: Tissue Spheroids as Building Blocks

Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography.

Recent advances in additive manufacturing facilitated the fabrication of parts with great geometrical complexity and relatively small size, and allowed for the fabrication of topologies that could not have been achieved using traditional fabrication techniques. In this work, we explore the topology-property relationship of several classes of periodic cellular materials; the first class is strut-based structures, while the second and third classes are derived from the mathematically created triply periodic minimal surfaces, namely; the skeletal-TPMS and sheet-TPMS cellular structures. Powder bed fusion technology was employed to fabricate the cellular structures of various relative densities out of Maraging steel. Scanning electron microscope (SEM) was also employed to assess the quality of the printed parts. Compressive testing was performed to deduce the mechanical properties of the considered cellular structures. Results showed that the sheet-TPMS based cellular structures exhibited a near stretching-dominated deformation behavior, while skeletal-TPMS showed a bending-dominated behavior. On the other hand, the Kelvin and Gibson-Ashby strut-based topologies exhibited a mixed mode of deformation while the Octet-truss showed a stretching-dominated behavior. Overall the sheet-TPMS based cellular structures showed superior mechanical properties among all the tested structures. The most interesting observation is that sheet-based Diamond TPMS structure showed the best mechanical performance with nearly independence of relative density. It was also observed that at decreased volume fractions the effect of geometry on the mechanical properties is more pronounced.

Topology-mechanical property relationship of 3D printed strut, skeletal, and sheet based periodic metallic cellular materials

Minimal surface scaffold designs for tissue engineering

Recently, computer aided geometric design of triply periodic minimal surfaces (TPMS) has received considerable attention in the area of computer aided nano design on account of its ability to efficiently construct a large number of complex surfaces. In this paper, a TPMS is described with periodic surfaces composed of simple trigonometric functions, thus enabling easy generation of TPMS for use in various mechanical, chemical, and physical applications. We first describe a TPMS with mesh surface using conventional marching cube algorithm. We then propose various related algorithms for generating complete solid model for various applications, ranging from thickened solid, through voxel solid, to complexshaped solid. The validity of this new technique is demonstrated for a variety of TPMSs, including the P, G, D, I-WP, F-RD, L, and I2-Y** surfaces. Finally, a new control approach for pore size distribution in tissue scaffold design is presented based on the pore-making element composed of TPMS and conformal refinement of all-hexahedral mesh in order to show the practical applicability of the newly suggested modeling approach.

Computer-aided porous scaffold design for tissue engineering using triply periodic minimal surfaces

Creating biophysically and biologically desirable porous scaffolds has always been one of the greatest challenges in tissue engineering (TE). Advanced additive manufacture (AM) methods such as three-dimensional (3D) printing techniques have established remarkable improvements in the fabrication of porous scaffolds and structures close in architecture to biological tissue. Such fabrication techniques have opened new areas of research in TE. Recently, it was shown that porous scaffolds which are mathematically designed by using triply periodic minimal surface (TPMS) pore geometry and fabricated through 3D printing techniques have remarkably high cell viability and mechanical strength when compared with conventional scaffolds. The enhanced cell adhesion, migration, and proliferation of TPMS-based scaffolds arise from the high surface area to volume ratio (SA/V ratio) that is a basic and fundamental concept of biology. Here, we report the design of multi-void TPMS-based scaffolds that dramatically increase the SA/V ratio of conventional TPMS scaffolds. Our findings suggest that the proposed novel design methodology can be applied to create a variety of computational models for prototyping and printing of biomimetic scaffolds and bioartificial tissues.

Advanced porous scaffold design using multi-void triply periodic minimal surface models with high surface area to volume ratios

Recently, a paradigm shift is taking place in tissue engineering scaffold design from homogeneous porous scaffolds to functionally graded scaffolds that have heterogeneous internal structures with controlled porosity levels and architectures. This paper presents a new heterogeneous modeling methodology for designing tissue engineering scaffolds with precisely controlled porosity and internal architectures using triply periodic minimal surfaces. The internal architectures and porosity at the spatial locations of the scaffolds are determined based on a given distribution of architectures and porosity levels specified at a few selected points on the model. After generating the hexahedral elements for a 3D anatomical shape using the distance field algorithm, the unit cell libraries composed of triply periodic minimal surfaces are mapped into the subdivided hexahedral elements using the shape function widely used in the finite element method. By simply allocating parameter values related to the porosity and architecture type to the corner nodes in each hexahedral element, we can easily and precisely control the pore size, porosity, and architecture type at each region of the scaffold while preserving perfectly interconnected pore networks across the entire scaffold.

Heterogeneous porous scaffold design for tissue engineering using triply periodic minimal surfaces

Additive manufacturing (AM) method has been a promising technique to produce three-dimensional (3D) tissue engineering scaffolds comprised of complex pore morphologies. Multi-functional scaffolds fabricated through AM techniques can provide outstanding combinations of mechanical and biological properties including stiffness, strength, toughness, and fluidic permeability. Among the various scaffold design methods, the pore morphology based on triply periodic minimal surface (TPMS) has been of great interest to many researchers due to its easy and accurate controllability on design parameters such as pore size, pore shape, volume fraction, and inner channel interconnectivity. In this paper, we propose a new multi-morphology scaffold design algorithm for building a wide variety of complex hybrid scaffolds composed of multiple TPMS morphologies and arbitrarily-shaped transition boundaries within one scaffold using the volumetric distance field (VDF) and the beta growth function (BGF). Through a variety of design results, we demonstrate the potential to design highly complex and heterogeneous scaffolds with enhancements in stiffness, strength, and permeability. In the method, the resulting scaffold hybrid morphology can be easily and accurately controlled to systematically explore a multitude of transition pore morphologies thereby enabling the optimization of multi-functional properties such as a combination of a high mechanical stiffness together with a high biological diffusion rate.

An advanced multi-morphology porous scaffold design method using volumetric distance field and beta growth function

Advances introduced by additive manufacturing (AM) methods referred to as solid freedom fabrication (SFF) or rapid prototyping (RP) methods have significantly improved the ability to fabricate porous scaffold structures close in architectures to biological tissues. These technologies have led to the development of innovative porous scaffolds and spatially complex artificial tissues. However, the current approaches face many challenges, such as the lack of an effective design software for printing and prototyping of tissues and scaffolds. In this article, a brief overview of the recent trends and challenges in computer-aided tissue engineering is provided. Future directions are also suggested in order to discuss the challenging technological barriers and provide the overall feasibility of prototyping and printing of biomimetic scaffolds and bioartificial tissues or organs.

Dong-Jin Yoo

Papers

Computer-aided porous scaffold design for tissue engineering using triply periodic minimal surfaces

Advanced porous scaffold design using multi-void triply periodic minimal surface models with high surface area to volume ratios

Heterogeneous porous scaffold design for tissue engineering using triply periodic minimal surfaces

An advanced multi-morphology porous scaffold design method using volumetric distance field and beta growth function

Recent trends and challenges in computer-aided design of additive manufacturing-based biomimetic scaffolds and bioartificial organs