TY  - JOUR
A1  - Pereira, Ana Rita
A1  - Lipphaus, Andreas
A1  - Ergin, Mert
A1  - Salehi, Sahar
A1  - Gehweiler, Dominic
A1  - Rudert, Maximilian
A1  - Hansmann, Jan
A1  - Herrmann, Marietta
T1  - Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell−Extracellular Matrix Interactions
JF  - Materials
N2  - In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.
KW  - bone tissue engineering
KW  - human trabecular bone decellularization
KW  - in vitro modeling
KW  - shear stress
KW  - compressive load
KW  - fluid simulation
KW  - cell-matrix interaction
KW  - mechanotransduction
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245012
SN  - 1996-1944
VL  - 14
IS  - 16
ER  - 
TY  - JOUR
A1  - Gensler, Marius
A1  - Leikeim, Anna
A1  - Möllmann, Marc
A1  - Komma, Miriam
A1  - Heid, Susanne
A1  - Müller, Claudia
A1  - Boccaccini, Aldo R.
A1  - Salehi, Sahar
A1  - Groeber-Becker, Florian
A1  - Hansmann, Jan
T1  - 3D printing of bioreactors in tissue engineering: A generalised approach
JF  - PLoS One
N2  - 3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.
KW  - stem cells
KW  - technology
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231368
VL  - 15
IS  - 11
ER  -