title: Synergistic effect of defined artificial extracellular matrices and pulsed electric fields on osteogenic differentiation of human MSCs.
abstract: In vivo, bone formation is a complex, tightly regulated process, influenced by multiple biochemical and physical factors. To develop a vital bone tissue engineering construct, all of these individual components have to be considered and integrated to gain an in vivo-like stimulation of target cells. The purpose of the present studies was to investigate the synergistic role of defined biochemical and physical microenvironments with respect to osteogenic differentiation of human mesenchymal stem cells (MSCs). Biochemical microenvironments have been designed using artificial extracellular matrices (aECMs), containing collagen I (coll) and glycosaminoglycans (GAGs) like chondroitin sulfate (CS), or a high-sulfated hyaluronan derivative (sHya), formulated as coatings on three-dimensional poly(caprolactone-co-lactide) (PCL) scaffolds. As part of the physical microenvironment, cells were exposed to pulsed electric fields via transformer-like coupling (TC). Results showed that aECM containing sHya enhanced osteogenic differentiation represented by increases in ALP activity and gene-expression (RT-qPCR) of several bone-related proteins (RUNX-2, ALP, OPN). Electric field stimulation alone did not influence cell proliferation, but osteogenic differentiation was enhanced if osteogenic supplements were provided, showing synergistic effects by the combination of sHya and electric fields. These results will improve the understanding of bone regeneration processes and support the development of effective tissue engineered bone constructs.
authors.affiliation: Max Bergmann Center of Biomaterials, Technische Universität Dresden, Budapester Straße 27, 01069 Dresden, Germany. ricarda.hess@tu-dresden.de
authors.forename: Ricarda
authors.initials: R
authors.lastname: Hess
authors.forename: Anna
authors.initials: A
authors.lastname: Jaeschke
authors.forename: Holger
authors.initials: H
authors.lastname: Neubert
authors.forename: Vera
authors.initials: V
authors.lastname: Hintze
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moeller
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Wiesmann
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: Dieter
authors.initials: D
authors.lastname: Scharnweber
mesh_terms: D000328:Adult; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D004558:Electric Stimulation; D005109:Extracellular Matrix / Q000737:chemistry*; D015870:Gene Expression; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D003094:Collagen