title: Student Award for Outstanding Research Winner in the Ph.D. Category for the 9th World Biomaterials Congress, Chengdu, China, June 1-5, 2012: The interplay of bone-like extracellular matrix and TNF-α signaling on in vitro osteogenic differentiation of mesenchymal stem cells.
abstract: As an initial step in the development of a bone tissue engineering strategy to rationally control inflammation, we investigated the interplay of bone-like extracellular matrix (ECM) and varying doses of the inflammatory cytokine tumor necrosis factor alpha (TNF-α) on osteogenically differentiating mesenchymal stem cells (MSCs) cultured in vitro on 3D poly(ε-caprolactone) (PCL) microfiber scaffolds containing pregenerated bone-like ECM. To generate the ECM, PCL scaffolds were seeded with MSCs and cultured in medium containing the typically required osteogenic supplement dexamethasone. However, since dexamethasone antagonizes TNF-α, the interplay of ECM and TNF-α was investigated by culturing naïve MSCs on the decellularized scaffolds in the absence of dexamethasone. MSCs cultured on ECM-coated scaffolds continued to deposit mineralized matrix, a late stage marker of osteogenic differentiation. Mineralized matrix deposition was not adversely affected by exposure to TNF-α for 4-8 days, but was significantly reduced after continuous exposure to TNF-α over 16 days, which simulates the in vivo response, where brief TNF-α signaling stimulates bone regeneration, while prolonged exposure has damaging effects. This underscores the exciting potential of PCL/ECM constructs as a more clinically realistic in vitro culture model to facilitate the design of new bone tissue engineering strategies that rationally control inflammation to promote regeneration.
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas 77251, USA.
authors.forename: Paschalia M
authors.initials: PM
authors.lastname: Mountziaris
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Tzouanas
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001363:Awards and Prizes; D001672:Biocompatible Materials; D035843:Biomedical Research; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D003226:Congresses as Topic; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013334:Students; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D014409:Tumor Necrosis Factor-alpha; C016240:polycaprolactone; D000469:Alkaline Phosphatase; D002118:Calcium