TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Kleinhans, Claudia
A1  - Mohan, Ramkumar
A1  - Vacun, Gabriele
A1  - Schwarz, Thomas
A1  - Haller, Barbara
A1  - Sun, Yang
A1  - Kahlig, Alexander
A1  - Kluger, Petra
A1  - Finne-Wistrand, Anna
A1  - Walles, Heike
A1  - Hansmann, Jan
T1  - A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects
JF  - Biotechnology journal
N2  - Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
KW  - bone substitute
KW  - critical size defect
KW  - perfusion bioreactor system
KW  - poly(LLA-co-CL) scaffold
KW  - tissue engineering
Y1  - 2015
SN  - 1860-6768
SS  - 1860-6768
U6  - https://doi.org/10.1002/biot.201400813
DO  - https://doi.org/10.1002/biot.201400813
VL  - 10
IS  - 11
SP  - 1727
EP  - 1738
S1  - 12
PB  - Wiley
CY  - Weinheim
ER  -