Development of Bioactive Scaffolds for Orthopedic Applications by Designing Additively Manufactured Titanium Porous Structures: A Critical Review
Source abstract
Abstract
We overview recent findings achieved in the field of model-driven development of additively manufactured porous materials for the development of a new generation of bioactive implants for orthopedic applications. Porous structures produced from biocompatible titanium alloys using selective laser melting can present a promising material to design scaffolds with regulated mechanical properties and with the capacity to be loaded with pharmaceutical products. Adjusting pore geometry, one could control elastic modulus and strength/fatigue properties of the engineered structures to be compatible with bone tissues, thus preventing the stress shield effect when replacing a diseased bone fragment. Adsorption of medicals by internal spaces would make it possible to emit the antibiotic and anti-tumor agents into surrounding tissues. The developed internal porosity and surface roughness can provide the desired vascularization and osteointegration. We critically analyze the recent advances in the field featuring model design approaches, virtual testing of the designed structures, capabilities of additive printing of porous structures, biomedical issues of the engineered scaffolds, and so on. Special attention is paid to highlighting the actual problems in the field and the ways of their solutions.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Bone Tissue Engineering Materials · Additive Manufacturing and 3D Printing Technologies · Additive Manufacturing Materials and Processes
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
N.N. Blokhin National Medical Research Center of Oncology (N.N. Blokhin NMRCO), Ministry of Health of the Russian Federation, 115478 Moscow, Russia
Department of Casting Technologies and Artistic Processing of Materials, National University of Science and Technology “MISIS”, 119049 Moscow, Russia
Laboratory for Metals and Alloys under Extreme Impacts, Ufa University of Science and Technology, 450076 Ufa, Russia
Laboratory for Dynamics and Extreme Characteristics of Promising Nanostructured Materials, Saint Petersburg State University, 199034 St. Petersburg, Russia
Funding
Russian Science Foundation
References (100+)
Show source-provided references
1. Additively manufactured metallic biomaterials
2. Vesvoranan, O., Anup, A., and Hixon, K.R. (2022). Current Concepts and Methods in Tissue Interface Scaffold Fabrication. Biomimetics, 7.10.3390/biomimetics7040151 ↗
3. Lv, Y., Wang, B., Liu, G., Tang, Y., Lu, E., Xie, K., Lan, C., Liu, J., Qin, Z., and Wang, L. (2021). Metal Material, Properties and Design Methods of Porous Biomedical Scaffolds for Additive Manufacturing: A Review. Front. Bioeng. Biotechnol., 9.10.3389/fbioe.2021.641130 ↗
4. Koju, N., Niraula, S., and Fotovvati, B. (2022). Additively Manufactured Porous Ti6Al4V for Bone Implants: A Review. Metals, 12.10.3390/met12040687 ↗
5. Properties and applications of additively manufactured metallic cellular materials: A review10.1016/j.pmatsci.2021.100918 ↗
6. The Biology of Fracture Healing10.1016/j.injury.2011.03.031 ↗
7. Newman, H., Shih, Y.V., and Varghese, S. (2021). Resolution of inflammation in bone regeneration: From understandings to therapeutic applications. Biomaterials, 277.10.1016/j.biomaterials.2021.121114 ↗
8. (2023, August 23). The Orthopaedic Industry Annual Report 2023. Available online: https://www.orthoworld.com/the-orthopaedic-industry-annual-report/.
9. Bioactivity—Symphony or Cacophony? A Personal View of a Tangled Field10.3390/prosthesis3010008 ↗
10. (2014). Implants for Surgery—In Vitro Evaluation for Apatite-Forming Ability of Implant Materials (Standard No. ISO 23317).
11. Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)10.1351/PAC-REC-10-12-04 ↗
12. Biology of Bone Sarcomas and New Therapeutic Developments10.1007/s00223-017-0372-2 ↗
13. Advances in immune checkpoint inhibitors for bone sarcoma therapy10.1016/j.jbo.2019.100221 ↗
14. Ma, X., Gao, Y., Zhao, D., Zhang, W., Zhao, W., Wu, M., Cui, Y., Li, Q., Zhang, Z., and Ma, C. (2022). Titanium Implants and Local Drug Delivery Systems Become Mutual Promoters in Orthopedic Clinics. Nanomaterials, 12.10.3390/nano12010047 ↗
15. New biomaterials for orthopedic implants
16. Strategies for creating living, additively manufactured, open-cellular metal and alloy implants by promoting osseointegration, osteoinduction and vascularization: An overview10.1016/j.jmst.2018.09.003 ↗
17. Engineered three-dimensional scaffolds for enhanced bone regeneration in osteonecrosis
18. Imran, R., Al Rashid, A., and Koç, M. (2022). Review on computational modeling for the property, process, product and performance (PPPP) characteristics of additively manufactured porous magnesium implants. Bioprinting, 28.10.1016/j.bprint.2022.e00236 ↗
19. A drug-loaded composite coating to improve osteogenic and antibacterial properties of Zn–1Mg porous scaffolds as biodegradable bone implants
20. Additive manufacturing of biodegradable magnesium-based materials: Design strategies, properties, and biomedical applications10.1016/j.jma.2022.12.001 ↗
21. Challenges and Solutions for the Additive Manufacturing of Biodegradable Magnesium Implants10.1016/j.eng.2020.02.015 ↗
22. The Additive Manufacturing (AM) of Titanium Alloys10.1016/j.mprp.2016.12.062 ↗
23. Antunes, L.H.M., and de Lima, C.R.P. (2018). Reference Module in Materials Science and Materials Engineering, Elsevier.
24. Goharian, A. (2017). Trauma Plating Systems, Elsevier.
25. Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur10.1016/S0021-9290(99)00111-6 ↗
26. Savio, D., and Bagno, A. (2022). When the total hip replacement fails: A review on the stress-shielding effect. Processes, 10.10.3390/pr10030612 ↗
27. Orthopedic implants and devices for bone fractures and defects: Past, present and perspective
28. Titanium alloys for biomedical applications10.1016/j.msec.2005.08.032 ↗
29. A topology strategy to reduce stress shielding of additively manufactured porous metallic biomaterials10.1016/j.ijmecsci.2021.106331 ↗
30. Effect of pore size on bone ingrowth into porous titanium implants fabricated by additive manufacturing: An in vivo experiment10.1016/j.msec.2015.10.069 ↗
31. Predicting permeability of regular tissue engineering scaffolds: Scaling analysis of pore architecture, scaffold length, and fluid flow rate effects10.1080/10255842.2016.1215436 ↗
32. Fluid permeability of graded porosity scaffolds architectured with minimal surfaces10.1021/acsbiomaterials.8b01400 ↗
33. Additive manufacturing of low-cost porous titanium-based composites for biomedical applications: Advantages, challenges and opinion for future development10.1016/j.jallcom.2020.154263 ↗
34. Synthetic bone: Design by additive manufacturing10.1016/j.actbio.2019.07.049 ↗
35. Kim, F.H., and Moylan, S.P. (2018). Literature Review of Metal Additive Manufacturing Defects, National Institute of Standards and Technology.10.6028/NIST.AMS.100-16 ↗
36. Quality Analysis in metal additive manufacturing with Deep Learning10.1007/s10845-020-01549-2 ↗
37. Additive manufacturing: A framework for implementation10.1016/j.ijpe.2013.07.008 ↗
38. Additive Manufacturing of Metals10.1016/j.actamat.2016.07.019 ↗
39. Additive manufacturing (3D printing): A review of materials, methods, applications and challenges10.1016/j.compositesb.2018.02.012 ↗
40. A Comprehensive Review on Additive Manufacturing of Medical Devices10.1007/s40964-021-00188-0 ↗
41. A comparative study on the nanoindentation behavior, wear resistance and in vitro biocompatibility of SLM manufactured CP–Ti and EBM manufactured Ti64 gyroid scaffolds10.1016/j.actbio.2019.08.008 ↗
42. Metallurgy principles applied to powder bed fusion 3D printing/additive manufacturing of personalized and optimized metal and alloy biomedical implants: An overview10.1016/j.jmrt.2019.12.015 ↗
43. Material-structure-performance integrated laser-metal additive manufacturing10.1126/science.abg1487 ↗
44. 3D printing in Personalized Drug Delivery: An overview of hot-melt extrusion-based fused deposition modeling10.1016/j.ijpharm.2021.120501 ↗
45. Additive manufacturing of titanium-based alloys—A review of methods, properties, challenges, and prospects10.1016/j.heliyon.2022.e09041 ↗
46. Farazin, A., Zhang, C., Gheisizadeh, A., and Shahbazi, A. (2023). 3D bio-printing for use as bone replacement tissues: A review of Biomedical Application. Biomed. Eng. Adv., 5.10.1016/j.bea.2023.100075 ↗
47. Laser spot size and scaling laws for laser beam additive manufacturing10.1016/j.jmapro.2021.10.053 ↗
48. Investigation of process by-products during the selective laser melting of Ti6Al4V powder
49. A review of critical repeatability and reproducibility issues in powder bed fusion10.1016/j.matdes.2019.108346 ↗
50. Process parameter optimization for removable partial denture frameworks manufactured by Selective Laser Melting10.1016/j.prosdent.2021.04.021 ↗
51. Densification behavior, microstructure evolution, and wear performance of selective laser melting processed commercially pure titanium10.1016/j.actamat.2012.04.006 ↗
52. Development and mechanical characterization of porous titanium bone substitutes10.1016/j.jmbbm.2012.01.008 ↗
53. Residual stresses and porosity in Ti-6Al-4V produced by laser powder bed fusion as a function of process atmosphere and component design
54. Study of Residual Stresses in Additively Manufactured Ti-6Al-4V by Neutron Diffraction Measurements10.1007/s11661-019-05538-w ↗
55. Dejene, N.D., and Lemu, H.G. (2023). Current Status and Challenges of Powder Bed Fusion-Based Metal Additive Manufacturing: Literature Review. Metals, 13.10.3390/met13020424 ↗
56. A study of the microstructural evolution during selective laser melting of Ti–6Al–4V10.1016/j.actamat.2010.02.004 ↗
57. Additive manufacturing of strong and ductile Ti–6Al–4V by selective laser melting via in situ martensite decomposition10.1016/j.actamat.2014.11.028 ↗
58. Microstructure and mechanical behavior of Ti–6Al–4V produced by rapid-layer manufacturing, for biomedical applications10.1016/j.jmbbm.2008.05.004 ↗
59. Microstructure and mechanical properties investigation of CP titanium processed by selective laser melting (SLM)10.1016/j.jmatprotec.2016.10.022 ↗
60. Binding mechanisms in selective laser sintering and Selective Laser melting10.1108/13552540510573365 ↗
61. Jin, B., Wang, Q., Zhao, L., Pan, A., Ding, X., Gao, W., Song, Y., and Zhang, X. (2023). A Review of Additive Manufacturing Techniques and Post-Processing for High-Temperature Titanium Alloys. Metals, 13.10.3390/met13081327 ↗
62. Wei, J., Sun, H., Zhang, D., Gong, L., Lin, J., and Wen, C. (2018). Influence of heat treatments on microstructure and mechanical properties of Ti–26Nb alloy elaborated in situ by laser additive manufacturing with Ti and Nb mixed powder. Materials, 12.10.3390/ma12010061 ↗
63. Heat treatment of ti6al4v produced by selective laser melting: Microstructure and mechanical properties10.1016/j.jallcom.2012.07.022 ↗
64. Peritectic Titanium Alloys for 3D Printing10.1038/s41467-018-05819-9 ↗
65. Surface and morphological modification of selectively laser melted titanium lattices using a chemical post treatment10.1016/j.surfcoat.2020.125794 ↗
66. A review on 3D printing process on metals and their surface roughness and dimensional accuracy10.1016/j.matpr.2022.05.018 ↗
67. Trapped powder removal from sheet-based porous structures based on triply periodic minimal surfaces fabricated by electron beam powder bed fusion10.1016/j.msea.2022.144479 ↗
68. Role of porosity defects in metal 3D printing: Formation Mechanisms, impacts on properties and mitigation strategies10.1016/j.mattod.2022.08.014 ↗
69. Gibson, L.J., Ashby, M.F., and Harley, B.A. (2010). Cellular Materials in Nature and Medicine, Cambridge University Press.
70. Simulation of cell seeding within a three-dimensional porous scaffold: A fluid-particle analysis10.1089/ten.tec.2011.0660 ↗
71. Lutzweiler, G., Ndreu Halili, A., and Engin Vrana, N. (2020). The Overview of Porous, Bioactive Scaffolds as Instructive Biomaterials for Tissue Regeneration and Their Clinical Translation. Pharmaceutics, 12.10.3390/pharmaceutics12070602 ↗
72. Numerical and experimental evaluation of TPMS gyroid scaffolds for bone tissue engineering10.1080/10255842.2019.1569638 ↗
73. Structural evaluation of scaffolds prototypes produced by three-dimensional printing10.1007/s00170-011-3219-4 ↗
74. Spatial optimization in perfusion bioreactors improves bone tissue-engineered construct quality attributes10.1002/bit.25303 ↗
75. Bertassoni, L.E., and Coelho, P.G. (2015). Engineering Mineralized and Load Bearing Tissues, Springer.10.1007/978-3-319-22345-2 ↗
76. A Review of the Selective Laser Melting Lattice Structures and Their Numerical Models10.1002/adem.202000611 ↗
77. SLM lattice structures: Properties, performance, applications and challenges10.1016/j.matdes.2019.108137 ↗
78. Mechanical and permeability properties of porous scaffolds developed by a Voronoi tessellation for bone tissue engineering10.1039/D2TB01478E ↗
79. Wu, Y., Wang, Y., Liu, M., Shi, D., Hu, N., and Feng, W. (2023). Mechanical Properties and in Vivo Assessment of Electron Beam Melted Porous Structures for Orthopedic Applications. Metals, 13.10.3390/met13061034 ↗
80. Compressive behavior assessment of a newly developed circular cell-based lattice structure10.1016/j.matdes.2021.109716 ↗
81. Advanced porous scaffold design using multi-void triply periodic minimal surface models with high surface area to volume ratios10.1007/s12541-014-0516-5 ↗
82. Additively manufactured metallic porous biomaterials based on minimal surfaces: A unique combination of topological, mechanical, and mass transport properties10.1016/j.actbio.2017.02.024 ↗
83. Shi, J., Wei, F., Chouraki, B., Sun, X., Wei, J., and Zhu, L. (2023). Study on Performance Simulation of Vascular-like Flow Channel Model Based on TPMS Structure. Biomimetics, 8.10.3390/biomimetics8010069 ↗
84. Multifunctional mechanical metamaterials based on triply periodic minimal surface lattices10.1002/adem.201900524 ↗
85. Functionally graded porous scaffolds in multiple patterns: New design method, physical and mechanical properties10.1016/j.matdes.2018.09.053 ↗
86. MSLattice: A free software for generating uniform and graded lattices based on triply periodic minimal surfaces
87. Du Plessis, A., Kouprianoff, D.-P., Yadroitsava, I., and Yadroitsev, I. (2018). Mechanical Properties and In Situ Deformation Imaging of Microlattices Manufactured by Laser Based Powder Bed Fusion. Materials, 11.10.20944/preprints201807.0616.v1 ↗
88. Biomedical applications of the powder-based 3D Printed Titanium Alloys: A Review10.1016/j.jmst.2021.11.084 ↗
89. Finite Element Analysis of Porous Commercially Pure Titanium for Biomedical Implant Application10.1016/j.msea.2018.04.009 ↗
90. Finite element modeling of porous titanium10.1016/j.ijsolstr.2006.04.020 ↗
91. Mechanical properties of open-cell metallic biomaterials manufactured using additive manufacturing10.1016/j.matdes.2013.01.071 ↗
92. A Prospect for Computing in Porous Materials Research: Very Large Fluid Flow Simulations10.1016/j.jocs.2015.11.013 ↗
93. Bermejillo Barrera, M.D., Franco-Martínez, F., and Díaz Lantada, A. (2021). Artificial Intelligence Aided Design of Tissue Engineering Scaffolds Employing Virtual Tomography and 3D Convolutional Neural Networks. Materials, 14.10.3390/ma14185278 ↗
94. Identification and ranking biomaterials for bone scaffolds using machine learning and PROMETHEE10.1007/s42600-022-00257-5 ↗
95. Jafari Chashmi, M., Fathi, A., Shirzad, M., Jafari-Talookolaei, R.-A., Bodaghi, M., and Rabiee, S.M. (2020). Design and analysis of porous functionally graded femoral prostheses with improved stress shielding. Designs, 4.10.3390/designs4020012 ↗
96. Vora, L.K., Gholap, A.D., Jetha, K., Thakur, R.R., Solanki, H.K., and Chavda, V.P. (2023). Artificial Intelligence in pharmaceutical technology and Drug Delivery Design. Pharmaceutics, 15.10.3390/pharmaceutics15071916 ↗
97. Machine learning-guided three-dimensional printing of tissue engineering scaffolds10.1089/ten.tea.2020.0191 ↗
98. Generating 3D porous structures using machine learning and additive manufacturing10.1016/j.matdes.2022.110858 ↗
99. Correlating in vitro performance with physico-chemical characteristics of nanofibrous scaffolds for skin tissue engineering using supervised machine learning algorithms10.1098/rsos.201293 ↗
100. Machine Learning in Tissue Engineering10.1089/ten.tea.2022.0128 ↗