Dual 3D printing for vascularized bone tissue regeneration

Sung Yun Hann; Haitao Cui; Timothy Esworthy; Xuan Zhou; Se-Jun Lee; Michael W Plesniak; Lijie Grace Zhang

doi:10.1016/j.actbio.2021.01.012

Dual 3D printing for vascularized bone tissue regeneration

Acta Biomater. 2021 Mar 15:123:263-274. doi: 10.1016/j.actbio.2021.01.012. Epub 2021 Jan 14.

Authors

Sung Yun Hann¹, Haitao Cui², Timothy Esworthy³, Xuan Zhou⁴, Se-Jun Lee⁵, Michael W Plesniak⁶, Lijie Grace Zhang⁷

Affiliations

¹ Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA. Electronic address: shann008@gwmail.gwu.edu.
² Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA. Electronic address: htcui@email.gwu.edu.
³ Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA. Electronic address: tesworthy@email.gwu.edu.
⁴ Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA. Electronic address: xzhou@email.gwu.edu.
⁵ Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA. Electronic address: sjlee@gwmail.gwu.edu.
⁶ Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA; Department of Biomedical Engineering, The George Washington University, Washington, DC 20052, USA. Electronic address: plesniak@gwu.edu.
⁷ Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA; Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052, USA; Department of Biomedical Engineering, The George Washington University, Washington, DC 20052, USA; Department of Medicine, The George Washington University, Washington, DC 20052, USA. Electronic address: lgzhang@email.gwu.edu.

PMID: 33454383
DOI: 10.1016/j.actbio.2021.01.012

Abstract

The development of sufficient vascular networks is crucial for the successful fabrication of tissue constructs for regenerative medicine, as vascularization is essential to perform the metabolic functions of tissues, such as nutrient transportation and waste removal. In recent years, efforts to 3D print vascularized bone have gained substantial attention, as bone disorders and defects have a marked impact on the older generations of society. However, conventional and previous 3D printed bone studies have been plagued by the difficulty in obtaining the nanoscale geometrical precision necessary to recapitulate the distinct characteristics of natural bone. Additionally, the process of developing truly biomimetic vascularized bone tissue has been historically complex. In this study, a biomimetic nano-bone tissue construct with a perfusable, endothelialized vessel channel was developed using a combination of simple stereolithography (SLA) and fused deposition modeling (FDM) 3D printing systems. The perfusable vessel channel was created within the SLA printed bone scaffold using an FDM printed polyvinyl alcohol (PVA) sacrificial template. Within the fabricated constructs, bone tissue was formed through the osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs), and distinct capillaries sprouted through the angiogenesis of the endothelialized vessel channel after human umbilical vein endothelial cells (HUVECs) had been perfused throughout. Furthermore, the fabricated constructs were evaluated in physiologically relevant culture conditions to predict tissue development after implantation in the human body. The experimental results revealed that the custom-designed bioreactor with an hMSC-HUVEC co-culture system enhanced the formation of vascular networks and the osteogenic maturation of the constructs for up to 20 days of observation.

Keywords: 3D printing; Biofabrication; Osteogenesis; Tissue regeneration; Vascular network.

Publication types

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

MeSH terms

Bone Regeneration
Bone and Bones
Human Umbilical Vein Endothelial Cells
Humans
Osteogenesis*
Printing, Three-Dimensional
Tissue Engineering
Tissue Scaffolds*