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Review
. 2021 Jun 24:16:4289-4319.
doi: 10.2147/IJN.S311001. eCollection 2021.

3D Printing of Micro- and Nanoscale Bone Substitutes: A Review on Technical and Translational Perspectives

Lijia Cheng  1 , Shoma Suresh K  2 , Hongyan He  1 , Ritu Singh Rajput  2 , Qiyang Feng  1 , Saravanan Ramesh  2 , Yuzhuang Wang  1 , Sasirekha Krishnan  2 , Serge Ostrovidov  3 , Gulden Camci-Unal  4 , Murugan Ramalingam  2
Affiliations
Review

3D Printing of Micro- and Nanoscale Bone Substitutes: A Review on Technical and Translational Perspectives

Lijia Cheng et al. Int J Nanomedicine. .

Abstract

Recent developments in three-dimensional (3D) printing technology offer immense potential in fabricating scaffolds and implants for various biomedical applications, especially for bone repair and regeneration. As the availability of autologous bone sources and commercial products is limited and surgical methods do not help in complete regeneration, it is necessary to develop alternative approaches for repairing large segmental bone defects. The 3D printing technology can effectively integrate different types of living cells within a 3D construct made up of conventional micro- or nanoscale biomaterials to create an artificial bone graft capable of regenerating the damaged tissues. This article reviews the developments and applications of 3D printing in bone tissue engineering and highlights the numerous conventional biomaterials and nanomaterials that have been used in the production of 3D-printed scaffolds. A comprehensive overview of the 3D printing methods such as stereolithography (SLA), selective laser sintering (SLS), fused deposition modeling (FDM), and ink-jet 3D printing, and their technical and clinical applications in bone repair and regeneration has been provided. The review is expected to be useful for readers to gain an insight into the state-of-the-art of 3D printing of bone substitutes and their translational perspectives.

Keywords: 3D printing; artificial bone; biomaterials; bone tissue engineering; nanomaterials.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
The schematic diagram of stereolithography appearance (SLA), selective laser sintering (SLS), fused deposition modeling (FDM), and ink-jet 3D printing techniques.
Figure 2
Figure 2
A photograph showing the resected specimen (Achilles tendon) and 3D printed titanium heel prosthesis used to replace the defect.
Figure 3
Figure 3
(A and B) Photographs of a 3D printed titanium prosthesis before implantation; (C and D) intraoperative photographs displaying the implant; (E and F) radiographs of the prosthesis.
Figure 4
Figure 4
Structures of polymeric biomaterials (A) PCL, (B) PLA, (C) PLGA, and (D) PEEK.
Figure 5
Figure 5
(A) Intraoperative images of the magnesium-PCL implant. (B) Bone graft. (C) Plate stabilization.
Figure 6
Figure 6
3D printed hydroxyapatite scaffold with defined macroporosity. Scale bars: 0.5 cm (A), 500 µm (B), and 5 µm (C).
Figure 7
Figure 7
(A) Extruded PBT/CNT composite filament. (B) 3D printed monolayer of PBT/CNT composite. (C) SEM image of the PBT/CNT monolayer illustrating the ridges. (D) Extruded PBT/G composite filament. (E) 3D printed monolayer of PBT/G composite. (F) SEM image of the PBT/G monolayer illustrating the ridges. Black scale bars are 1 cm and white scale bars are 500 μm.
Figure 8
Figure 8
SEM Images of nanocomposite scaffold architecture following extrusion with 400-µm diameter nozzle. (A) Top view of single layer print; (B) side view of seven-layer print displaying inter-layer spacing and lateral spacing between fibers; (CandD) cross-sectional view of single fibers following biopsy from the macrostructure.
Figure 9
Figure 9
In vitro studies on bioactive nanocomposite scaffolds. (A) hMSCs seeded on 3D scaffolds proliferated over one week. The effect of nano silicate on hMSCs differentiation was evaluated by monitoring. (B) ALP activity and production of mineralized matrix. The presence of nanosilicates upregulated the peak ALP activity (Day 14) and production of a mineralized matrix (Day 21). ***P<0.001.
Figure 10
Figure 10
Uniformly formed highly porous interconnected network via the combination of indirect 3D printing and foaming processes. (A-D) Indirect fabrication can be combined with a foaming process to produce highly and uniformly porous gelatin scaffolds with complex channel architectures. (E and F) The order of this structure can be improved further by incorporating monodispersed microspheres into the casting process.
Figure 11
Figure 11
(A) The implantation process of a 3D printed scaffold for bone defects of rabbits. (B) Microstructure of human cortical bone. (C) Schematic diagram of the channel structure which is an ideal space for bone tissue ingrowth; a channel structure has been observed along with the black arrow. (D) Gross morphology of the 3d-printed scaffold (E) Photo of the side of the printed scaffold. (F) Photo of the top surface of the printed scaffold. (G) The channel is shown in the sketch map of the 3d-printed scaffold structure.
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References

    1. Baroli B. From natural bone grafts to tissue engineering therapeutics: brainstorming on pharmaceutical formulative requirements and challenges. J Pharm Sci. 2009;98(4):1317–1375. doi:10.1002/jps.21528 - DOI - PubMed
    1. Wang H, Xu T, Shou B. Determination of material strengths by Hydraulic Bulge Test. Mater (Basel, Switzerland). 2016;10(1):23. doi:10.3390/ma10010023 - DOI - PMC - PubMed
    1. Laurencin C, Khan Y, El-Amin SF. Bone graft substitutes. Expert Rev Med Devices. 2006;3(1):49–57. doi:10.1586/17434440.3.1.49 - DOI - PubMed
    1. Jimi E, Hirata S, Osawa K, Terashita M, Kitamura C, Fukushima H. The current and future therapies of bone regeneration to repair bone defects. Int J Dent. 2012;2012:1–7. doi:10.1155/2012/148261 - DOI - PMC - PubMed
    1. Kashte S, Jaiswal AK, Kadam S. Artificial bone via bone tissue engineering: current scenario and challenges. Tissue Eng Regen Med. 2017;14(1):1–14. doi:10.1007/s13770-016-0001-6 - DOI - PMC - PubMed