Stem Cell-Based Bone Tissue Engineering with a Hydrogel Scaffold Shows Promise for Bone Repair
This paper found improved scaffolds for mesenchymal stem cells (MSCs) led to better bone regeneration.
ABSTRACT
Stem Cell Res Ther. 2019 Aug 14;10(1):254. doi: 10.1186/s13287-019-1350-6.
Author Information
- Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
- McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA.
- Molecular Therapeutics Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
- Present Address: Center for Pulmonary Vascular Biology and Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
- Present Address: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
- Molecular Therapeutics Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. [email protected].
- McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA. [email protected].
- Department of Orthopaedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine, 450 Technology Drive, Pittsburgh, PA, 15219, USA. [email protected].
- McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA. [email protected].
- Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA. [email protected].
- Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. [email protected].
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 bonemorphogenetic 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 additional 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.
Conclusion
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.