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Perfusion Bioreactor Culture of Bone Marrow Stromal Cells Enhances Cranial Defect Regeneration

Gandhi, Jarel K., Ph.D.; Kao, Shu-Wei, B.Sc.; Roux, Brianna M., Ph.D.; Rodriguez, Raul A., B.Sc.; Tang, Shu-Jun, M.Sc.; Fisher, John P., Ph.D.; Cheng, Ming-Huei, M.D., M.B.A.; Brey, Eric M., Ph.D.

Plastic and Reconstructive Surgery: May 2019 - Volume 143 - Issue 5 - p 993e–1002e
doi: 10.1097/PRS.0000000000005529
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Background: Cell-seeded biomaterial scaffolds have been proposed as a future option for reconstruction of bone tissue. The ability to generate larger, functional volumes of bone has been a challenge that may be addressed through the use of perfusion bioreactors. In this study, the authors investigated use of a tubular perfusion bioreactor system for the growth and differentiation of bone marrow stromal (mesenchymal stem) cells seeded onto fibrin, a highly angiogenic biomaterial.

Methods: Cells were encapsulated within fibrin beads and cultured either within a tubular perfusion bioreactor system or statically for up to 14 days. Scaffolds were analyzed for osteogenic differentiation. A rodent cranial defect model (8-mm diameter) was used to assess the bone regeneration of scaffolds cultured in the bioreactor, statically, or used immediately after formation. Immunohistochemistry was used to visualize CD31+ vessel density. Micro–computed tomographic imaging was used to visualize mineral formation within the defect volume.

Results: Tubular perfusion bioreactor system–cultured samples showed significantly greater osteodifferentiation, indicated by an increase in VEGF expression and mineral deposition, compared with statically cultured samples. Increased expression of OPN, RUNX2, VEGF, and CD90 was seen over time in both culture methods. After implantation, bioreactor samples exhibited greater bone formation and vessel density compared with all other groups. Analysis of micro–computed tomographic images showed full union formation through the greatest diameter of the defect in all bioreactor samples and the highest levels of mineralized volume after 8 weeks.

Conclusion: Mesenchymal stem cells encapsulated in fibrin beads and cultured in the tubular perfusion bioreactor system resulted in increased vascularization and mineralized tissue formation in vivo relative to static culture.

San Antonio, Texas; Taoyuan, Taiwan; and College Park, Md.

From the Department of Biomedical Engineering, The University of Texas at San Antonio; the Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, and the Center for Tissue Engineering, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University; the Fischell Department of Bioengineering, University of Maryland; and Research Services, South Texas Veterans Health Care System.

Received for publication October 11, 2017; accepted September 27, 2018.

Disclosure:The authors have no financial interest to declare in relation to the content of this article.

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Ming-Huei Cheng, M.D., M.B.A., Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Kueishan, Taoyuan 33305, Taiwan, minghueicheng@gmail.com, Facebook: Ming-huei Cheng, Instagram: @dr_minghuei_cheng

©2019American Society of Plastic Surgeons