Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair
| العنوان: | Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair |
|---|---|
| المؤلفون: | Daniel S. Alt, Honghyun Park, Yuxuan Cheng, Joel D. Boerckel, P. C. Wong, Felicia He, Anna D. Dikina, Samuel Herberg, Yu Bin Lee, Phuong N. Dang, Alexandra McMillan, Rui Tang, James H. Dawahare, Eben Alsberg, Daniel Varghai, Kentaro Umemori, Anna M. McDermott, Jung Youn Shin |
| المصدر: | Science Advances |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, animal structures, Long bone, 02 engineering and technology, Bone and Bones, Transforming Growth Factor beta1, 03 medical and health sciences, Tissue engineering, Biomimetics, Osteogenesis, Transforming Growth Factor beta, In vivo, Morphogenesis, medicine, Animals, Humans, Endochondral ossification, Cells, Cultured, Research Articles, 030304 developmental biology, 0303 health sciences, Bone Development, Multidisciplinary, Tissue Engineering, Chemistry, Regeneration (biology), Mesenchymal stem cell, SciAdv r-articles, Mesenchymal Stem Cells, 021001 nanoscience & nanotechnology, Rats, Cell biology, medicine.anatomical_structure, embryonic structures, Synthetic Biology, 0210 nano-technology, Function (biology), Research Article, Morphogen |
| الوصف: | Mesenchymal condensations promote defect repair by mimicking cellular, morphogenetic, and mechanical aspects of bone development. Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation, directed by local morphogen signals and mechanical cues. Here, we aimed to mimic development for regeneration of large bone defects. We hypothesized that engineered human mesenchymal condensations presenting transforming growth factor–β1 (TGF-β1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles promotes endochondral defect regeneration contingent on in vivo mechanical cues. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with BMP-2 + TGF-β1 fully restoring mechanical function. Delayed in vivo ambulatory loading significantly enhanced the bone formation rate in the dual morphogen group. In vitro, BMP-2 or BMP-2 + TGF-β1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-β1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering. |
| تدمد: | 2375-2548 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d60f8942e445a052dfb5cdf82e165d23 https://doi.org/10.1126/sciadv.aax2476 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d60f8942e445a052dfb5cdf82e165d23 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
|---|