3D Bioprinting of a Bioactive Composite Scaffold for Cell Delivery in Periodontal Tissue Regeneration

Guohou Miao; Liyu Liang; Wenzhi Li; Chaoyang Ma; Yuqian Pan; Hongling Zhao; Qing Zhang; Yin Xiao; Xuechao Yang

doi:10.3390/biom13071062

3D Bioprinting of a Bioactive Composite Scaffold for Cell Delivery in Periodontal Tissue Regeneration

Biomolecules. 2023 Jun 30;13(7):1062. doi: 10.3390/biom13071062.

Authors

Guohou Miao^{1

2}, Liyu Liang³, Wenzhi Li^{1

2}, Chaoyang Ma^{1

2}, Yuqian Pan^{1

2}, Hongling Zhao^{1

2}, Qing Zhang^{1

2

4}, Yin Xiao^{1

5

6}, Xuechao Yang^{1

2}

Affiliations

¹ Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China.
² School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China.
³ Hospital of Stomatology, Zhongshan 528404, China.
⁴ Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, 1081 BT Amsterdam, The Netherlands.
⁵ School of Medicine and Dentistry, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia.
⁶ The Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, QLD 4000, Australia.

Abstract

Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.

Keywords: 3D bioprinting; cell-laden scaffold; composite hydrogel; periodontal regeneration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bioprinting* / methods
Dogs
Hydrogels / chemistry
Mice
Osteogenesis*
Tissue Engineering / methods
Tissue Scaffolds / chemistry

Substances

Hydrogels

Grants and funding

This work was funded by the Natural Science Foundation of Guangdong Province (No. 2023A1515012777), the Science and Technology Planning Project of Guangzhou City, China (No. 202102080227, 202201020203,202201020117) and the Special projects in key fields of Guangdong Colleges and Universities, China (No. 2021ZDZX2058).