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ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 12 - 2024 |
doi: 10.3389/fbioe.2024.1436519
Biofabrication of prevascularized spheroids for bone tissue engineering by fusion of microvascular fragments with osteoblasts
Provisionally accepted- 1 Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany
- 2 Department of Trauma, Hand and Reconstructive Surgery, Saarland University, Homburg, Germany
- 3 Department of Molecular, Cell and Systems Biology, College of Natural and Agricultural Sciences, University of California, Riverside, Riverside, California, United States
Spheroids are promising building blocks for scaffold-free bone tissue engineering. Their rapid vascularization is of major importance to guarantee their survival after transplantation. To achieve this, we herein introduce the biofabrication of prevascularized spheroids by fusion of adipose tissue-derived microvascular fragments (MVF) with osteoblasts (OB). For this purpose, 200 MVF from donor mice and 5,000, 10,000 or 20,000 murine OB (MC3T3-E1) were co-cultured in a liquid overlay system for 3 days to generate OB + MVF spheroids. OB mono-culture spheroids served as controls. During the generation process, the diameters of all spheroids progressively decreased, resulting in compact, viable spheroids of homogeneous sizes. MVF promoted the maturation of spheroids containing 5,000 OB, as shown by an accelerated decline of cell proliferation due to contact inhibition. Moreover, MVF most effectively reassembled into new microvascular networks within these small spheroids when compared to the other spheroid types, indicating the most beneficial MVF to OB ratio. Accordingly, these spheroids also showed a high angiogenic sprouting activity in vitro. In contrast to OB spheroids, they further rapidly vascularized in vivo after transplantation into dorsal skinfold chambers. This was caused by the interconnection of incorporated MVF with surrounding blood vessels. These findings indicate that OB + MVF spheroids may be suitable for bone tissue engineering, which should be next tested in appropriate in vivo bone defect models.
Keywords: microvascular fragments, Osteoblasts, spheroid, Bone, Tissue Engineering, vascularization
Received: 22 May 2024; Accepted: 29 Aug 2024.
Copyright: © 2024 Wrublewsky, Schultz, Ammo, Bickelmann, Metzger, Später, Pohlemann, Menger and Laschke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Matthias W. Laschke, Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany
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