Claudia Kleinhans1,2,3, Ramkumar Ramani Mohan4,5,3, Gabriele Vacun5, Thomas Schwarz5, Barbara Haller6, Yang Sun7, Alexander Kahlig2, Petra J. Kluger5, Anna Finne‐Wistrand7, Heike Walles4,5, Jan Hansmann4,5
1Department of Orthopedics, Medical University Graz, Graz, Austria
2Institute for Interfacial Process Engineering and Plasma Technology IGVP, University of Stuttgart, Stuttgart, Germany
3these authors contributed equally to this work
4Chair Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
5Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department
6FH Esslingen, Esslingen am Neckar, Germany
7Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Tóm tắt
AbstractCritical 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.
