TY - JOUR
T1 - Biomimetic mineralization promotes viability and differentiation of human mesenchymal stem cells in a perfusion bioreactor
AU - Ramírez-Rodríguez, Gloria Belén
AU - Pereira, Ana Rita
AU - Hermann, Marietta
AU - Hansmann, Jan
AU - Delgado-López, José Manuel
AU - Sprio, Simone
AU - Tampieri, Anna
AU - Sandri, Monica
N1 - Funding Information:
Funding: This research was funded by the EU Marie Curie Project ‘‘Bio-Inspired Bone Regeneration’’ (BIOINSPIRE: Grant No. 607051, FP7-PEOPLE-2013-ITN) and Spanish Ministry of Science, Innovation and Universities (MCIU) with projects NanoSmart (RYC-2016-21042) and NanoVIT (RTI-2018-095794-A-C22). G.B.R.R. acknowledges to MCIU for her postdoctoral contract within Juan de la Cierva Program (JdC-2017). R.P. and M.H. are funded by the Interdisciplinary Center for Clinical Research (IZKF) at the University of Wuerzburg (Project D-361).
Funding Information:
This research was funded by the EU Marie Curie Project ??Bio-Inspired Bone Regeneration?? (BIOINSPIRE: Grant No. 607051, FP7-PEOPLE-2013-ITN) and Spanish Ministry of Science, Innovation and Universities (MCIU) with projects NanoSmart (RYC-2016-21042) and NanoVIT (RTI-2018-095794-A-C22). G.B.R.R. acknowledges to MCIU for her postdoctoral contract within Juan de la Cierva Program (JdC-2017). R.P. and M.H. are funded by the Interdisciplinary Center for Clinical Research (IZKF) at the University of Wuerzburg (Project D-361).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM.
AB - In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM.
KW - Apatite nanoparticles
KW - Collagen
KW - Human mesenchymal stem cell
KW - Magnesium
KW - Osteogenesis
KW - Perfusion bioreactor
KW - Scaffold
KW - Extracellular Matrix/metabolism
KW - Apatites/chemistry
KW - Humans
KW - Cell Survival/drug effects
KW - Spectroscopy, Fourier Transform Infrared
KW - X-Ray Microtomography
KW - Mesenchymal Stem Cells/cytology
KW - Tissue Scaffolds
KW - Biomimetics
KW - Culture Media
KW - Bone Marrow Cells/cytology
KW - Magnesium/chemistry
KW - Biocompatible Materials/chemistry
KW - Cell Differentiation/drug effects
KW - Tissue Engineering/methods
KW - Thermogravimetry
KW - Cell Culture Techniques/instrumentation
KW - Cell Lineage
KW - Bioreactors
KW - Perfusion
KW - Nanoparticles/chemistry
KW - Porosity
KW - Collagen/chemistry
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UR - http://www.scopus.com/inward/citedby.url?scp=85100133225&partnerID=8YFLogxK
U2 - 10.3390/ijms22031447
DO - 10.3390/ijms22031447
M3 - Article
C2 - 33535576
AN - SCOPUS:85100133225
SN - 1661-6596
VL - 22
SP - 1
EP - 15
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 3
M1 - 1447
ER -