@article{2f378fa4032046d9bc23f04ec49254b1,
title = "Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair",
abstract = "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–1 (TGF-1) 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-1 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-1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.",
author = "S. Herberg and McDermott, {A. M.} and Dang, {P. N.} and Alt, {D. S.} and R. Tang and Dawahare, {J. H.} and D. Varghai and Shin, {J. Y.} and A. McMillan and Dikina, {A. D.} and F. He and Lee, {Y. B.} and Y. Cheng and K. Umemori and Wong, {P. C.} and H. Park and Boerckel, {J. D.} and E. Alsberg",
note = "Funding Information: We thank the staff of the Freimann Life Science Center at the University of Notre Dame (ND) and the Animal Resource Center at Case Western Reserve University (CWRU) for animal care and husbandry. We also thank the staff of the ND Integrated Imaging Facility and the CWRU Imaging Research Core Facility for imaging support, E. M. Greenfield at the CWRU Orthopaedic Research Facilities for imaging and biomechanical testing support, and A. Awadallah at the CWRU Histology Core Facility for technical support. We also thank X. Yu and W. L. Murphy at the University of Wisconsin, Madison, WI for providing the MCM. Funding: We gratefully acknowledge funding from the NIH{\textquoteright}s National Institute of Dental and Craniofacial Research (F32DE024712 to S.H.), National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR066193, R01AR063194, and R01AR069564 to E.A. and T32AR007505 to D.S.A.), National Heart, Lung, and Blood Institute (T32HL134622 to R.T.), National Institute of Biomedical Imaging and Bioengineering (R01EB023907 to E.A.), National Center for Advancing Translational Sciences (TL1 TR000441 to D.S.A.), the Ohio Biomedical Research Commercialization Program under award number TECG20150782 (to E.A.), the Naughton Foundation (to A.M.M. and J.D.B.), and the Indiana Clinical and Translational Sciences Institute, grant number UL1TR001108 from the NIH (to J.D.B.). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Publisher Copyright: Copyright {\textcopyright} 2019 The Authors, some rights reserved;",
year = "2019",
month = aug,
doi = "10.1126/sciadv.aax2476",
language = "English",
volume = "5",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "8",
}