Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Efficient in vivo bone formation by BMP-2 engineered human mesenchymal stem cells encapsulated in a projection stereolithographically fabricated hydrogel scaffold

Lin, Hang and Tang, Ying and Lozito, Thomas P. and Oyster, Nicholas and Wang, Bing and Tuan, Rocky S. (2019) Efficient in vivo bone formation by BMP-2 engineered human mesenchymal stem cells encapsulated in a projection stereolithographically fabricated hydrogel scaffold. Stem Cell Research & Therapy, 10 (1). ISSN 1757-6512

[img] PDF
Download (4MB)


Background: Stem cell-based bone tissue engineering shows promise for bone repair but faces some challenges,
such as insufficient osteogenesis and limited architecture flexibility of the cell-delivery scaffold.

Methods: In this study, we first used lentiviral constructs to transduce ex vivo human bone marrow-derived stem cells with human bone morphogenetic protein-2 (BMP-2) gene (BMP-hBMSCs). We then introduced these cells into a hydrogel scaffold using an advanced visible light-based projection stereolithography (VL-PSL) technology, which is compatible with concomitant cell encapsulation and amenable to computer-aided architectural design, to fabricate scaffolds fitting local physical and structural variations in different bones and defects.

Results: The results showed that the BMP-hBMSCs encapsulated within the scaffolds had high viability with sustained BMP-2 gene expression and differentiated toward an osteogenic lineage without the supplement of dditional BMP-2 protein. In vivo bone formation efficacy was further assessed using an intramuscular implantation model in severe combined immunodeficiency (SCID) mice. Microcomputed tomography (micro-CT) imaging indicated rapid bone formation by the BMP-hBMSC-laden constructs as early as 14 days post-implantation. Histological examination revealed a mature trabecular bone structure with considerable vascularization. Through tracking of the implanted cells, we also found that BMP-hBMSC were directly involved in the new bone formation.

Conclusions: The robust, self-driven osteogenic capability and computer-designed architecture of the construct developed in this study should have potential applications for customized clinical repair of large bone defects or non-unions.

Keywords: Osteogenesis, Bone tissue engineering, Bone formation, 3D bioprinting, Gene therapy, Ex vivo gene


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Lozito, Thomas
Oyster, Nicholas
Tuan, Rocky
Date: 2019
Date Type: Publication
Journal or Publication Title: Stem Cell Research & Therapy
Volume: 10
Number: 1
Publisher: Springer Nature
DOI or Unique Handle: 10.1186/s13287-019-1350-6
Schools and Programs: Swanson School of Engineering > Bioengineering
Swanson School of Engineering > Mechanical Engineering and Materials Science
Refereed: Yes
ISSN: 1757-6512
Official URL:
Funders: Department of Defense, National Institutes of Health, Commonwealth of Pennsylvania Department of Health, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine
Article Type: Research Article
Date Deposited: 12 May 2020 15:06
Last Modified: 12 May 2020 15:06


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item