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 - Hoboken, NJ ER -