Additively manufactured metallic biomaterials

Abstract

Metal additive manufacturing (AM) has led to an evolution in the design and fabrication of hard tissue substitutes, enabling personalized implants to address each patient's specific needs. In addition, internal pore architectures integrated within additively manufactured scaffolds, have provided an opportunity to further develop and engineer functional implants for better tissue integration, and long-term durability. In this review, the latest advances in different aspects of the design and manufacturing of additively manufactured metallic biomaterials are highlighted. After introducing metal AM processes, biocompatible metals adapted for integration with AM machines are presented. Then, we elaborate on the tools and approaches undertaken for the design of porous scaffold with engineered internal architecture including, topology optimization techniques, as well as unit cell patterns based on lattice networks, and triply periodic minimal surface. Here, the new possibilities brought by the functionally gradient porous structures to meet the conflicting scaffold design requirements are thoroughly discussed. Subsequently, the design constraints and physical characteristics of the additively manufactured constructs are reviewed in terms of input parameters such as design features and AM processing parameters. We assess the proposed applications of additively manufactured implants for regeneration of different tissue types and the efforts made towards their clinical translation. Finally, we conclude the review with the emerging directions and perspectives for further development of AM in the medical industry.

Keywords: Additive manufacturing; Biomaterials; Metal implant; Porous scaffold; Tissue engineering.

Graphical abstract

Fig. 1

The most widely used metal additive manufacturing processes for fabrication of metal implants. (A) Laser powder bed fusion (LPBF), (B) electron beam powder bed fusion (EPBF), (C) Directed energy deposition (DED) with blown powder, and (D) binder jetting (BJ) process.

Fig. 2

Topology optimization approaches utilized for design of bone replacements. (A) Topology optimized pelvic prosthesis for four resection types. Reproduced with permission from Ref. [9]. Copyright 2019, Elsevier. (B) Stress-based topology optimized temporomandibular prosthesis showing different sections of the design. Reproduced with permission from Ref. [152]. Copyright 2017, Scientific Research Publishing (C) Venous-like topologies after applying perimeter control constraint. Reproduced with permission from Ref. [137]. Copyright 2018, Elsevier.

Fig. 3

Design strategies for the scaffolds with stochastic structures. (A) Porosity design based on connecting random points in the design volume. Reproduced with permission from Ref. [165]. Copyright 2018, Elsevier. (B) Voronoi-tessellation diagrams in (i) two-dimension (2D) and (ii) three-dimension (3D). Reproduced with permission from Ref. [167]. Copyright 2021, Elsevier. (iii) Design steps based on 3D Voronoi-Tessellation and (iv) controlling irregularity of the random geometries. Reproduced with permission from Ref. [172]. Copyright 2018, American Chemical Society.

Fig. 4

Examples and mechanical properties of additively manufactured metal lattice structures. (A) Schematic illustration of famous lattice network topologies. (B) Unit cells are marked with red rectangle and pore sizes are represented with blue circles in each lattice design. Reproduced with permission from Ref. [188]. Copyright 2017, Public Library of Science. (C) Stress-strain curves of (i) cube and (ii) diamond lattice. (iii) Yield strength and elastic modulus change with relative density for various conventional lattice structures. Reproduced with permission from Ref. [185]. Copyright 2021, Elsevier. (D) The stress-strain curves of (i) auxetic and (ii) conventional lattices. Reproduced with permission from Ref. [187]. Copyright 2018, Royal Society of Chemistry.

Fig. 5

Mechanical characterization of triply periodic minimal surface (TPMS)-based scaffolds manufactured by metal additive manufacturing (AM) techniques. (A) Solid and sheet-based gyroid topologies with various relative densities. Reproduced with permission from Ref. [194]. Copyright 2020, Elsevier. (B) (i) Schwarz P (P), gyroid (G), and diamond (D) unit cell geometries. Pore sizes are demonstrated in yellow. (ii) Relative compressive modulus changes with porosity and (iii) Surface area changes with unit cell size. Reproduced with permission from Ref. [196]. Copyright 2018, American Chemical Society. (C) (i) Failure mechanism of P, G, and D scaffolds. (ii) Elastic modulus and compressive strength change with relative density. (iii) Stress-strain curves of the D-surface scaffolds with various unit cell sizes. Reproduced with permission from Ref. [208], Copyright 2021, American Chemical Society.

Fig. 6

Examples of functionally graded scaffolds designed to meet conflicting requirements in bone constructs. (A) Stochastic porous scaffold with gradient porosity designed based on the bone's local stiffness. Reproduced with permission from Ref. [175]. Copyright 2019, Elsevier. (B) The steps for generating porous scaffolds using probability spheres with various sizes based on Voronoi-Tessellation approach. Reproduced with permission from Ref. [172]. Copyright 2018, Applied Chemical Society. (C) The sheet-based gyroid architecture with (i) graded porosity generated by varying the sheet thickness and (ii) unit cell size. Reproduced with permission from Ref. [194]. Copyright 2020, Elsevier. (D) Localized stiffness design within the scaffold by changing the sheet thickness to mimic specific tissue types. Reproduced with permission from Ref. [196]. Copyright 2018, American Chemical Society. (E) Bone regeneration within the scaffolds with various pore sizes including (i) 300–500 μm, (ii) 200–600 μm, (iii) 100–700 μm, and (iv) non-porous after the (v) implantation surgery. (vi) Bone volume per total volume and (vii) push-out force (N) of the scaffolds. Reproduced with permission from Ref. [216]. Copyright 2019, Elsevier.

Fig. 7

Examples of porous metallic biomaterials with pore shape gradient. (A) Multiple topologies within the sheet-based TPMS scaffold with a smooth transition from diamond to gyroid. Reproduced with permission from Ref. [194]. Copyright 2020, Elsevier. (B) Hybrid implant designs including conventional and auxetic lattices with various internal angles. Reproduced with permission from Ref. [187]. Copyright 2018, Royal Society of Chemistry.

Fig. 8

Examples of the material gradient in metal additive manufacturing (AM) of biomedical structures. (A) Laser melting deposition of Ti–6Al–4V reinforced with TiC particles with various TiC concentrations from 0% to 50% from bottom to top. Reproduced with permission from Ref. [231]. Copyright 2017, Elsevier. (B) Laser-engineered net shaping of multi-material structure with layers of pure Ti–6Al–4V, Ti–6Al–4V + Al₂O₃, and pure Al₂O₃. Reproduced with permission from Ref. [232]. Copyright 2018, Elsevier.

Fig. 9

Classification of different defect types commonly occur in the microstructure of metallic additively manufactured implants (involving nodes and struts) in terms of their sources, components affected, and their effects.

Fig. 10

Structural defects in additively manufactured metal implants. (A) Printability of the triply periodic minimal surface (TPMS) with P and D topologies at various unit cell sizes and macroporosity. Reproduced with permission from Ref. [208]. Copyright 2021, American Chemical Society. (B) Deviation of additively manufactured P and D scaffolds from the computer-aided design (CAD) models. The green color represents a deviation of less than 0.1 mm. Reproduced with permission from Ref. [208]. Copyright 2021, American Chemical Society. (C) (i-iii) heterogeneous thickness, waviness, and misalignment of the structs in a lattice structure. Reproduced with permission from Ref. [237]. Copyright 2017, Elsevier. (iv) Parasitic mass on the nodes. Reproduced with permission from Ref. [243]. Copyright 2020, Cambridge University Press. (D) (i-iii) Aggregation of unmolten powder bonded to the hanging features. Reproduced with permission from Ref. [208]. Copyright 2021, American Chemical Society. (iv) Bonded powders (yellow arrow), stair-step defect (pink arrow), and porosity defect (blue arrow). Reproduced with permission from Ref. [243]. Copyright 2020, Cambridge University Press. (v) Heat transfer in the laser powder bad fusion (LPBF) process resulting in powder bonding defect in the hanging features. Reproduced with permission from Ref. [252]. Copyright 2018, Multidisciplinary Digital Publishing Institute. (E) X-ray tomography of the LPBF processed structure showing the trapped keyhole micropores within the solid phase. Reproduced with permission from Ref. [208]. Copyright 2021, American Chemical Society. Defects in the structures due to the (ii) entrapped gas porosity, (iii) incomplete melting, (iv) lack of fusion (LOF), and (v) cracks. Reproduced with permission from Ref. [246]. Copyright 2019, Wiley-VCH.

Fig. 11

Classification of methods for minimization of AM defects.

Fig. 12

Fatigue and impact responses in metal implants. (A) Lattice structure (i) after the fatigue test and (ii) the location of the fatigue crack initiation. Detection of fatigue crack propagation in Ti2448 lattice structure using scanning electron microscopy (SEM)-based electron backscatter diffraction (EBSD) technique showing (iii) morphology of single β grains and (iv) EBSD analysis of the struts along the building direction. Reproduced with permission from Ref. [268]. Copyright 2017, Elsevier. (B) Failure modes in (i) P, I-WP, gyroid, and diamond under (ii) static compression loading and (iii) fatigue test. The shear lines are represented in purple. Barreling and diagonal collapsing of layers are highlighted in green. Reproduced with permission from Ref. [270]. Copyright 2017, Elsevier. (C) The hip implant setup for (i) distraction, (ii) fatigue. (iii) Reaction force on the implant's neck. (iv) Crack initiation and fracture locations in the solid hip implant. Reproduced with permission from Ref. [274]. Copyright 2016, Wiley-VCH. (D) Dental implant (i) assembly and (ii) fatigue test setup. (iii) Crack region on the screw thread of the dental implant after fatigue test. (iv) External load-fatigue life (F–N) data for the dental implants under various screw tightening torques. Reproduced with permission from Ref. [275]. Copyright 2020, Multidisciplinary Digital Publishing Institute.

Fig. 13

Permeability analysis of porous metal additively manufactured scaffolds. (A) (i) Permeability setup for measuring the permeability of triply periodic minimal surface (TPMS) cubic scaffolds with P, G, and D topologies at different (ii) unit cell sizes and (iii) porosities. The value beside P, G, and D illustrate the porosity of the scaffolds and P0.25–0.75 represent the scaffolds with gradient macroporosity. Reproduced with permission from Ref. [208]. Copyright 2021, American Chemical Society. (B) Permeability analysis of TPMS scaffolds with G topology. (i) The schematic diagram of permeability setup. (ii) Permeability changes with flow rate for the scaffolds with various pore sizes. The samples labeled with C05, C07, C09, C11, and C13 have pore sizes of 500, 700, 900, 1100, and 1300 μm. (iii) Pressure distribution, (iv) velocity distribution, and (v) velocity distribution within vertical and horizontal cross-sections of the scaffold. Reproduced with permission from Ref. [284]. Copyright 2020, Elsevier.

Fig. 14

Application of metal additive manufacturing (AM) for skeletal bone implants. (A) Metallic pelvic prosthesis fabricated by electron beam powder bed fusion (EPBF) technology. Reproduced with permission from Ref. [308]. Copyright 2019, Springer Nature. (B) Fracture fixation in the pelvis by an additively manufactured metallic prosthesis. Reproduced with permission from Ref. [308]. Copyright 2019, Springer Nature. (C) Functionally graded porous metallic hip implant for biopermeability (higher designed macroporosity at the periphery) and enhanced mechanical strength (lower macroporosity at the center) can be integrated with cell-laden gelatin methacryloyl (GelMA) due to its high peripheral permeability. Reproduced with permission from Ref. [208]. Copyright 2021, American Chemical Society. (D) Hybrid hip implants including conventional and auxetic lattice topologies to prevent implant retraction from the bone. Reproduced with permission from Ref. [187]. Copyright 2018, Royal Society of Chemistry. (E) Deformable orthopedic implants architected with conventional lattice design at various relative densities. Reproduced with permission from Ref. [185]. Copyright 2021, Elsevier.

Fig. 15

Applications of metal additive manufacturing (AM) in spinal cord tissue regeneration. (A) Anterior column reconstruction using a customized metal prosthesis fabricated by electron beam powder bed fusion (EPBF) technology. The prosthesis includes a lattice design at the center of the implant that mimics cancellous bone and a fine shell to resemble the cortical bone. Reproduced with permission from Ref. [314]. Copyright 2018, Springer Nature. (B) Customized 3D printed prosthesis to bridge the unstable parts to the nearest stable vertebra. Reproduced with permission from Ref. [315]. Copyright 2019, Elsevier. (C) Reconstructing large vertebral defects using a 3D printed metal prosthesis. Reproduced with permission from Ref. [318]. Copyright 2019, Elsevier. (D) Porous self-stabilizing vertebral body prosthesis. Reproduced with permission from Ref. [317]. Copyright 2014, Lippincott Williams & Wilkins.

Fig. 16

Applications of metal AM in craniofacial implants and maxillofacial reconstructions. (A) Design steps for (i) bulk cranial implant and converting to (ii) porous implant. (iii) 3D printed metallic cranial implant on the skull. Reproduced with permission from Ref. [320]. Copyright 2017, Elsevier. (B) Customized models of cranial implants and guide for non-human primates. Reproduced with permission from Ref. [322]. Copyright 2017, Elsevier. (C) Customized V-shaped craniomaxillofacial 3D-printed metallic implant. Reproduced with permission from Ref. [323]. Copyright 2020, Elsevier. (D) (i) Designing 3D human mandible porous model. (ii) Metal 3D printed mandibular scaffold. (iii) Mechanical characterization of the mandibular scaffold after implantation. After 12 months from implantation, the strength of the implant was about the strength of the native mandible. Reproduced with permission from Ref. [321]. Copyright 2018, Springer Nature.

Fig. 17

Application of metal AM in dental implants. (A) The design and experimental steps for a three-dimensional (3D) printed metallic dental implant. Reproduced with permission from Ref. [328]. Copyright 2020, Elsevier. (B) (i) 3D printed metallic maxillary and mandibular base for dentures (ii) Complete denture including the metallic base. Reproduced with permission from Ref. [336]. Copyright 2020, Elsevier. (C) Surface functionalization of the dental implants for improved osseointegration and controlling the peri-implantitis issues. Reproduced with permission from Ref. [337]. Copyright 2019, Multidisciplinary Digital Publishing Institute.