File(s) stored somewhere else
Please note: Linked content is NOT stored on University of Notre Dame and we can't guarantee its availability, quality, security or accept any liability.
Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair
journal contribution
posted on 2019-10-14, 00:00 authored by A McMillan, A D Dikina, A.M. McDermott, D. Varghai, D.S. Alt, E. Alsberg, F. He, H. Park, J-Y. Shin, J.D. Boerckel, J.H. Dawahare, K. Umemori, P.C. Wong, P.N. Dang, R. Tang, S. Herberg, Y Cheng, Y LeeEndochondral 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.
History
Date Modified
2019-10-29Language
- English
Publisher
AAASUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC