Combinatorial morphogenetic and mechanical cues to mimic bone development for defect repair.
Animals
Biomimetics
/ methods
Bone Development
/ physiology
Bone and Bones
/ metabolism
Cells, Cultured
Humans
Male
Mesenchymal Stem Cells
/ metabolism
Morphogenesis
/ physiology
Osteogenesis
/ physiology
Rats
Tissue Engineering
Transforming Growth Factor beta
/ metabolism
Transforming Growth Factor beta1
/ metabolism
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
06
03
2019
accepted:
19
07
2019
entrez:
7
9
2019
pubmed:
7
9
2019
medline:
12
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31489377
doi: 10.1126/sciadv.aax2476
pii: aax2476
pmc: PMC6713501
doi:
Substances chimiques
Transforming Growth Factor beta
0
Transforming Growth Factor beta1
0
transforming growth factor beta1.2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaax2476Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR074948
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007250
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007829
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR002549
Pays : United States
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