Advances in Filament Structure of 3D Bioprinted Biodegradable Bone Repair Scaffolds

Abstract

Conventional bone repair scaffolds can no longer meet the high standards and requirements of clinical applications in terms of preparation process and service performance. Studies have shown that the diversity of filament structures of implantable scaffolds is closely related to their overall properties (mechanical properties, degradation properties, and biological properties). To better elucidate the characteristics and advantages of different filament structures, this paper retrieves and summarizes the state of the art in the filament structure of the three-dimensional (3D) bioprinted biodegradable bone repair scaffolds, mainly including single-layer structure, double-layer structure, hollow structure, core-shell structure and bionic structures. The eximious performance of the novel scaffolds was discussed from different aspects (material composition, ink configuration, printing parameters, etc.). Besides, the additional functions of the current bone repair scaffold, such as chondrogenesis, angiogenesis, anti-bacteria, and anti-tumor, were also concluded. Finally, the paper prospects the future material selection, structural design, functional development, and performance optimization of bone repair scaffolds.

Keywords: 3D printing; Bone repair scaffolds; Filament structure; Mechanical properties.

Figure 1

Schematic diagrams of classical scaffold structures. (A) Optical images and Micro-CT images of CSi-Mg/TCP scaffold after sintering[85]. (Reprinted from Journal of the European Ceramic Society, 36, Shao H, He Y, Fu J, et al., 3D printing magnesium-doped wollastonite/β-TCP bioceramics scaffolds with high strength and adjustable degradation, 1495-1503, Copyright (2016), with permission from Elsevier) (B) Schematic diagram of the micro-nanostructure surface fabrication process of BRT scaffold[86]. (Reprinted from Deng C, Lin R, Zhang M, et al., Advanced Functional Materials, Copyright^© 1999-2021 John Wiley and Sons, Inc). (C) Schematic diagram of HA scaffold surface morphology[87]. (from ref[87] licensed under Creative Commons Attribution 4.0 license) (D) Local SEM images of bionic HA/TCP[88]. (Bio-Design and Manufacturing, 3D printing of hydroxyapatite/tricalcium phosphate scaffold with hierarchical porous structure for bone regeneration, 3, 2020, 15-29, Li X, Yuan Y, Liu L, et al., © 2021 Springer Nature Switzerland AG. With permission of Springer). (E) Schematic diagram of low-temperature 3D printed and AP and OP cross-linked TCP/PLGA scaffolds[89]. (from ref.[89] licensed under Creative Commons Attribution 4.0 license). (F) Finished PCL (left) and PCL/β-TCP (right) scaffolds[90]. (Reprinted from Pae H, Kang J, Cha J, et al., Journal of Biomedical Materials Research Part B: Applied Biomaterials, Copyright © 1999-2021 John Wiley and Sons, Inc).

Figure 2

Schematic diagram of bilayer scaffold structure. (A) Schematic diagram of CHA scaffold printing[5]. (Reprinted with permission from Lin K F, He S, Song Y, et al. Low-Temperature Additive Manufacturing of Biomimic Three-Dimensional Hydroxyapatite/Collagen Scaffolds for Bone Regeneration. ACS Applied Materials and Interfaces. 2016; 8(11):6905-6916. Copyright© 2016 American Chemical Society). (B) Schematic diagram of scaffold printing by LBL method[91]. Reprinted with permission from Shao H, Ke X, Liu A, et al., Biofabrication,2017; 9(2):025003, ©Copyright 2021 IOP Publishing (C) Schematic diagram of cell-carrying α-TCP/collagen scaffold printing[92]. (Reprinted from Journal of the European Ceramic Society, 36, Shao H, He Y, Fu J, et al., 3D printing magnesium-doped wollastonite/β-TCP bioceramics scaffolds with high strength and adjustable degradation, 1495-1503, Copyright (2016) with permission from Elsevier). (D) Schematic diagram of CSi+PVA+Metal ion bilayer scaffold[93]. (Reprinted from Journal of the Mechanical Behavior of Biomedical Materials, 104, Alksne M, Kalvaityte M, Simoliunas E, et al. In vitro comparison of 3D printed polylactic acid/hydroxyapatite and polylactic acid/bioglass composite scaffolds: Insights into materials for bone regeneration, Copyright© 2021, with permission from Elsevier) (E) Schematic diagram of PLA/PLA+HA/PLA+BG bilayer scaffold[94]. (From ref.[94] licensed under Creative Commons Attribution 4.0 license).

Figure 3

Schematic diagram of hollow structure scaffold. (A) Schematic diagram of Lotus-like structure scaffold[95]. (from ref.[95] licensed under Creative Commons Attribution 4.0 license). (B) Schematic diagram of Haversian-like bone scaffold structure[96]. (from ref.[96] licensed under Creative Commons Attribution Non-Commercial License 4.0 (CC BY-NC) (C) Schematic diagram of non-porous, monoporous and porous scaffold prepared from apatite material[97]. (Reprinted with permission from Wang X, Lin M, Kang Y. Engineering Porous β-Tricalcium Phosphate (β-TCP) Scaffolds with Multiple Channels to Promote Cell Migration, Proliferation, and Angiogenesis. ACS Applied Materials and Interfaces. 2019; 11(9):9223-9232. Copyright© 2019 American Chemical Society) (D) Schematic diagram of nut-like scaffold structure prepared from NICE bioink[98]. (Reprinted with permission from Chimene D, Miller L, Cross L M, et al. Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue. ACS Applied Materials and Interfaces. 2020; 12(14):15976-15988. Copyright© 2020 American Chemical Society) (e) Schematic diagram of scaffold composed of highly microporous hollow filament structure[99]. (Reprinted from Journal of the European Ceramic Society, 35(16), Moon Y W, Choi I J, Koh Y H, et al., Macroporous alumina scaffolds consisting of highly microporous hollow filaments using three-dimensional ceramic/camphene-based co-extrusion, 4623-4627., Copyright © 2015, with permission from Elsevier) (F) Schematic diagram of GelMA porous gel scaffold[100]. (From ref.[100] licensed under Creative Commons Attribution 4.0 license).

Figure 4

Schematic diagram of the core-shell structure scaffold. (A) SEM images of CaSi, CaP core-shell structure[101]. (Reprinted with permission from Ke X, Zhuang C, Yang X, et al. Enhancing the Osteogenic Capability of Core-Shell Bilayered Bioceramic Microspheres with Adjustable Biodegradation, ACS Applied Materials and Interfaces. 2017; 9(29):24497-24510, Copyright © 2017 American Chemical Society) (B) Schematic diagram of GPT-50 and HUVEC hybrid scaffold printing[102]. (Reprinted from Pistry P, Aied A, Alexander M, et al., Macromolecular Bioscience, Copyright © 1999-2021 John Wiley and Sons). (C) Printed schematic of the cell-loaded hydrogel core-shell structure scaffold[103]. (from ref.[103] licensed under Creative Commons Attribution 4.0 license). (D) Schematic diagram of the CSi+PVA+Metal ion core-shell structure scaffold[92]. (Reprinted from Journal of the European Ceramic Society, 36, Shao H, He Y, Fu J, et al., 3D printing magnesium-doped wollastonite/β-TCP bioceramics scaffolds with high strength and adjustable degradation, 1495-1503, Copyright (2016), with permission from Elsevier) (E) Printed schematic of the GelMA-loaded dual-cell scaffold[104]. Reproduced from ref.[104] with permission from The Royal Society of Chemistry.

Figure 5

Schematic diagrams of other scaffold structures. (A) Schematic diagram of GML+TGL material mimic lotus pod scaffold structure[106]. (From ref.[106] licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) (B) Schematic diagram of cell-carrying spring-like scaffold structure[107]. (Reprinted with permission from Gao Q, Liu Z, Lin Z, et al., 3D Bioprinting of Vessel-like Structures with Multi-level Fluidic Channels, ACS Biomaterials Science and Engineering. 2017; 3(3):399-408. Copyright© 2017 American Chemical Society) (C) Schematic diagram of hexagonal mimic scaffold structure[108]. Reprinted with permission from Ma X, Xin Q, Wei Z, et al. Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proceedings of the National Academy of Sciences. 2016; 113(8):2206. (D) Light microscope images of multi-shape GelMA[109]. Adapted from Xie, M., Yu, K., Sun, Y., Shao, L., Nie, J., Gao, Q., Qiu, J., Fu, J., Chen, Z., He, Y. Protocols of 3D Bioprinting of Gelatin Methacryloyl Hydrogel Based Bioinks. J. Vis. Exp. (154), e60545, doi:10.3791/60545 (2019) (E) Schematic diagram of multi-layered helical cylindrical scaffold structure[110]. Reprinted with permission from Xue J M, Feng C, Xia LG, et al. Assembly Preparation of Multilayered Biomaterials with High Mechanical Strength and Bone-Forming Bioactivity. Chemistry of Materials. 2018; 30(14):4646-4657, Copyright^© 2018 American Chemical Society.