Fabrication of centimeter-sized 3D constructs with patterned endothelial cells through assembly of cell-laden microbeads as a potential bone graft

Guang Yang; Bhushan Mahadik; Ji Young Choi; Justine R Yu; Trevor Mollot; Bin Jiang; Xiaoming He; John P Fisher

doi:10.1016/j.actbio.2020.11.040

Fabrication of centimeter-sized 3D constructs with patterned endothelial cells through assembly of cell-laden microbeads as a potential bone graft

Acta Biomater. 2021 Feb:121:204-213. doi: 10.1016/j.actbio.2020.11.040. Epub 2020 Dec 1.

Authors

Guang Yang¹, Bhushan Mahadik¹, Ji Young Choi¹, Justine R Yu², Trevor Mollot³, Bin Jiang⁴, Xiaoming He⁴, John P Fisher⁵

Affiliations

¹ Tissue Engineering & Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD 20742, United States; NIBIB/NIH Center for Engineering Complex Tissues, University of Maryland, College Park, MD 20742, United States.
² Tissue Engineering & Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD 20742, United States; NIBIB/NIH Center for Engineering Complex Tissues, University of Maryland, College Park, MD 20742, United States; University of Maryland School of Medicine, Baltimore, MD 21201, United States.
³ Tissue Engineering & Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD 20742, United States.
⁴ Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD 20742, United States.
⁵ Tissue Engineering & Biomaterials Laboratory, Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD 20742, United States; NIBIB/NIH Center for Engineering Complex Tissues, University of Maryland, College Park, MD 20742, United States. Electronic address: jpfisher@umd.edu.

Abstract

Modular tissue engineering is a promising biofabrication strategy to create engineered bone grafts in a bottom-up manner, in which cell-laden micro-modules are prepared as basic building blocks to assemble macroscopic tissues via different integrating mechanisms. In this study, we prepared collagen microbeads loaded with human bone marrow derived mesenchymal stem cells (BMSCs) using a microfluidic approach. The cell-laden microbeads were characterized for size change, cell activity, osteogenesis, as well as their self-assembly properties to generate centimeter-sized constructs. Moreover, using the cell-laden beads as a supporting medium, induced pluripotent stem cell-derived endothelial cells (iPSC-EC) were patterned inside bead aggregates through extrusion-based 3D printing. This fabrication approach that combines modular tissue engineering and supports 3D printing has the potential to create 3D engineered bone grafts with a pre-existing, customized vasculature.

Keywords: 3D printing; Bone tissue engineering; Induced pluripotent stem cell; Mesenchymal stem cell; Modular tissue engineering.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Endothelial Cells*
Humans
Mesenchymal Stem Cells*
Microspheres
Osteogenesis
Tissue Engineering
Tissue Scaffolds

Grants and funding

P41 EB023833/EB/NIBIB NIH HHS/United States