TY  - JOUR
A1  - Bernhard, Jonathan C
A1  - Marolt Presen, Darja
A1  - Li, Ming
A1  - Monforte, Xavier
A1  - Ferguson, James
A1  - Leinfellner, Gabriele
A1  - Heimel, Patrick
A1  - Betti, Susanne L
A1  - Shu, Sharon
A1  - Teuschl-Woller, Andreas H
A1  - Tangl, Stefan
A1  - Redl, Heinz
A1  - Vunjak-Novakovic, Gordana
T1  - Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts
JF  - Cells
N2  - Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks. The pathways' constructs were evaluated over time with respect to gene expression, composition, histomorphology, microstructure, vascularization and biomechanics. Hypertrophic chondrocytes expressed higher levels of osteogenic genes and deposited significantly more bone mineral and proteins than the osteoblasts. Before implantation, the mineral in the hyper group was less mature than that in the osteo group. Following 12 weeks of implantation, the hyper group had increased mineral density but a similar overall mineral composition compared with the osteo group. The hyper group also displayed significantly more blood vessel infiltration than the osteo group. Both groups contained M2 macrophages, indicating bone regeneration. These data suggest that, similar to the body's repair processes, endochondral pathway might be more advantageous when regenerating large defects, whereas intramembranous ossification could be utilized to guide the tissue formation pattern with a scaffold architecture.
KW  - bone tissue engineering
KW  - endochondral
KW  - mesenchymal stromal cells
KW  - ossification
KW  - intramembranous
Y1  - 
U6  - http://dx.doi.org/10.3390/cells11193070
VL  - 11
IS  - 19:3070
ER  -