Injectable Stem Cell‐Laden Photocrosslinkable Microspheres Fabricated Using Microfluidics for Rapid Generation of Osteogenic Tissue Constructs |
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| Authors: | Xin Zhao Shen Liu Lara Yildirimer Hong Zhao Ruihua Ding Huanan Wang Wenguo Cui David Weitz |
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| Affiliation: | 1. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA;2. The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi, China;3. Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, China;4. Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China;5. Centre for Nanotechnology and Regenerative Medicine, UCL Division of Surgery and Interventional Science, University College London, London, UK;6. Department of Orthopedics, the First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, Jiangsu, China;7. Department of Physics, Harvard University, Cambridge, 02138, USA |
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| Abstract: | Direct injection is a minimally invasive method of stem cell transplantation for numerous injuries and diseases. However, despite its promising potential, its clinical translation is difficult due to the low cell retention and engraftment after injection. With high versatility, high‐resolution control and injectability, microfabrication of stem‐cell laden biomedical hydrogels holds great potential as minimally invasive technology. Herein, a strategy of microfluidics‐assisted technology entrapping bone marrow‐derived mesenchymal stem cells (BMSCs) and growth factors in photocrosslinkable gelatin (GelMA) microspheres to ultimately generate injectable osteogenic tissue constructs is presented. Additionally, it is demonstrated that the GelMA microspheres can sustain stem cell viability, support cell spreading inside the microspheres and migration from the interior to the surface as well as enhance cell proliferation. This finding shows that encapsulated cells have the potential to directly and actively participate in the regeneration process. Furthermore, it is found that BMSCs encapsulated in GelMA microspheres show enhanced osteogenesis in vitro and in vivo, associated with a significant increase in mineralization. In short, the proposed strategy can be utilized to facilitate bone regeneration with minimum invasiveness, and can potentially be applied along with other matrices for extended applications. |
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| Keywords: | bone marrow‐derived mesenchymal stem cells microfluidics microspheres osteogenesis photocrosslinkable gelatin |
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