Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun 24;7(3):367.
doi: 10.18063/ijb.v7i3.367. eCollection 2021.

3D Bioprinting Photo-Crosslinkable Hydrogels for Bone and Cartilage Repair

Affiliations
Review

3D Bioprinting Photo-Crosslinkable Hydrogels for Bone and Cartilage Repair

Quanjing Mei et al. Int J Bioprint. .

Abstract

Three-dimensional (3D) bioprinting has become a promising strategy for bone manufacturing, with excellent control over geometry and microarchitectures of the scaffolds. The bioprinting ink for bone and cartilage engineering has thus become the key to developing 3D constructs for bone and cartilage defect repair. Maintaining the balance of cellular viability, drugs or cytokines' function, and mechanical integrity is critical for constructing 3D bone and/or cartilage scaffolds. Photo-crosslinkable hydrogel is one of the most promising materials in tissue engineering; it can respond to light and induce structural or morphological transition. The biocompatibility, easy fabrication, as well as controllable mechanical and degradation properties of photo-crosslinkable hydrogel can meet various requirements of the bone and cartilage scaffolds, which enable it to serve as an effective bio-ink for 3D bioprinting. Here, in this review, we first introduce commonly used photo-crosslinkable hydrogel materials and additives (such as nanomaterials, functional cells, and drugs/cytokine), and then discuss the applications of the 3D bioprinted photo-crosslinkable hydrogel scaffolds for bone and cartilage engineering. Finally, we conclude the review with future perspectives about the development of 3D bioprinting photo-crosslinkable hydrogels in bone and cartilage engineering.

Keywords: Bone and cartilage engineering; Hydrogel; Photo-crosslinking; Three-dimensional printing.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of photo-crosslinkable hydrogels for bioprinting bone and cartilage tissues.
Figure 2
Figure 2
Construction of 3D mimetic bone tissue by 3D bioprinting. (Ai) Schematic diagram of the structure of a native bone; design and fabrication of the engineered vascularized bone structure. (Aii) Schematic diagram of the microstructure of vascularized construct based on matrix metalloproteinase (MMP)-sensitive GelMA hydrogel, the formation of vascular lumen, and capillary network in different regions[70]. (Reproduced from H. Cui, W. Zhu, M. Nowicki, et al., Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs Via Dual 3D Bioprinting: Integrating Regional Bioactive Factors Into Architectural Design, Wiley. © 2016 WILEY-VCH Verlag GmbH Co. KgaA Weinheim). (Bi) Schematic diagram of a complex bone structure. (Bii) Schematic diagram of the fabrication process of complex bone construct through 3D bioprinting strategy. (Biii) Illustration of bioprinted cell-laden hydrogel cylinders through an SLA bioprinter[6]. (Reproduced from B. Byambaa, N. Annabi, K. Yue, et al., Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue Wiley. © 2017 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim).
Figure 3
Figure 3
Construction of 3D mimetic cartilage tissue by 3D bioprinting. (A) Schematic representation of a core/shell 3D printing by co-axial extrusion printer and confocal images of 3D printed core/shell structure[73] (from ref.[73] licensed under Creative Commons Attribution 4.0 license with permission). (Bi) Representative images of 3D constructs printed through an in situ crosslinking method. (Bii) Histological staining of printed cartilage constructs; left image shows the representative staining images and right image shows quantification analysis in different culture time. Scale bar = 100 μm[74] (from ref.[74] licensed under Creative Commons Attribution 4.0 license). (C) Detection of proteoglycans in printed constructs after 14 days of incubation (red: proteoglycans; green to blue: nuclei and other ECM/bio-ink). Porcine chondrocytes were embedded in gelatin (i, ii, iii) and hyaluronic acid (iv, v, vi) bio-inks. Scale bar = 500 μm[75] (from ref.[75] licensed under Creative Commons Attribution-Non Commercial 4.0).
Figure 4
Figure 4
Construction of 3D mimetic osteochondral tissue by 3D bioprinting. (A) Schematic diagram of the biohybrid gradient scaffolds for osteochondral regeneration. (B) Mechanical properties of poly (nacryloyl 2-glycine) -GelMA hydrogels: (i) tensile strength and (ii) compressive strength. (C) Genetic analysis for osteochondral differentiation: (i and ii) Expression of cartilage-related genes (COL II, aggrecan, SOX-9, and COL I) and (iii-iv) expression of osteogenesis-related genes (ALP, OCN, COL I, and RUNX2) after 7 and 14 days of culture, respectively[79] (from ref.[79] licensed under Creative Commons Attribution 4.0 license).
Figure 5
Figure 5
Construction of 3D bioprinted hydrogels in bone disease model. (A) Fabrication of a musculoskeletal interface model: (i) Schematic diagram of a native insertion site; (ii) illustration of the printing model; (iii) a representative image showing the bioprinted structure; (iv) fluorescent image of the bioprinted structure; blue: osteoblasts, red: MSCs, and green: Fibroblasts[84]. (Reproduced from A. K. Miri, D. Nieto, L. Iglesias, et al., Microfluidics-Enabled Multimaterial Maskless Stereolithographic Bioprinting from Wiley. © 2018 WILEY-VCH Verlag GmbH Co. KgaA Weinheim). (B) Illustration of 3D bioprinted PEGDA bone matrix model for breast cancer cell invasion research[85]. (Reprinted from Nanomed-Nanotechnol,12(1), W. Zhu, B. Holmes, R. I. Glazer, et al., 3D Printed Nanocomposite Matrix for The Study of Breast Cancer Bone Metastasis, 69 – 79, Copyright (2016), with permission from Elsevier). (C) Schematic diagram of 3D bioprinted GelMA bone matrix model for breast cancer metastasis study[86]. (Reprinted with permission from X. Zhou, W. Zhu, M. Nowicki, et al., Acs Appl Mater Inter, 2016, 8(44): 30017 – 30026, Copyright (2016) American Chemical Society).

Similar articles

Cited by

References

    1. Midha S, Dalela M, Sybil D, et al. Advances in Three-dimensional Bioprinting of Bone:Progress and Challenges. J Tissue Eng Regen Med. 2019;13:925–45. https://doi.org/10.1002/term.2847. - PubMed
    1. Liu Y, Luo D, Wang T. Hierarchical Structures of Bone and Bioinspired Bone Tissue Engineering. Small. 2016;12:4611–32. https://doi.org/10.1002/smll.201600626. - PubMed
    1. Bai X, Gao M, Syed S, et al. Bioactive Hydrogels For Bone Regeneration. Bioact Mater. 2018;3:401–17. - PMC - PubMed
    1. Mandrycky C, Wang Z, Kim K, et al. 3D Bioprinting for Engineering Complex Tissues. Biotechnol Adv. 2016;34:422–34. https://doi.org/10.1016/j.biotechadv.2015.12.011. - PMC - PubMed
    1. Allen MR, Burr DB. Basic and Applied Bone Biology. Amsterdam, Netherlands: Elsevier; 2014. Bone Modeling and Remodeling; pp. 75–90. https://doi.org/10.1016/b978-0-12-416015-6.00004-6.

LinkOut - more resources