title: Osteogenic Differentiation Evaluation of an Engineered Extracellular Matrix Based Tissue Sheet for Potential Periosteum Replacement.
abstract: Due to the indispensable role of periosteum in bone defect healing and regeneration, a promising method to enhance osteogenesis of bone grafts by using an engineered biomimetic periosteum would be highly beneficial. The stromal microenvironment of periosteum is composed of various highly organized extracellular matrix (ECM) fibers, so an aligned natural ECM sheet, derived from the human dermal fibroblast cell sheet, may be advantageous when applied for artificial periosteum fabrication. Human mesenchymal stem cells (hMSCs) have been used to replace the osteoprogenitor cell population in native periosteum due to hMSCs' great osteogenic potential and fast in vitro expansion capacity. The objective of this work is to investigate if the natural ECM sheet and the substrate alignment can promote in vitro osteogenesis of hMSCs. The conventional cell culture substrates collagen I-coated polydimethylsiloxane (PDMS) and tissue culture plastic (TCP) were used as controls. It was found that the ECM sheet significantly increased alkaline phosphatase activity and calcium deposition. The enhanced osteogenic potential was further confirmed by increased bone-specific gene expression. The ECM sheet can bind significantly higher amounts of growth factors including ANG-1, TGF-β1, bFGF, and VEGF, as well as calcium phosphate nanoparticles, which contributed to high osteogenesis of the hMSCs on ECM sheet. However, the alignment of the substrates did not show significant influence on osteogenic activity and growth factor binding. These results demonstrated the great potential of hMSC-seeded ECM sheet as a biomimetic periosteum to improve critical sized bone regeneration.
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University , 1400 Townsend Drive, Houghton, Michigan 49931, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University , 1400 Townsend Drive, Houghton, Michigan 49931, United States.
authors.forename: Zichen
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University , 1400 Townsend Drive, Houghton, Michigan 49931, United States.
authors.forename: Baratwaaj
authors.initials: B
authors.lastname: Kannan
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University , 1400 Townsend Drive, Houghton, Michigan 49931, United States.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Tahtinen
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University , 1400 Townsend Drive, Houghton, Michigan 49931, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000327:Adsorption; D000469:Alkaline Phosphatase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010521:Periosteum / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: aligned substrate; biomimetic periosteum; extracellular matrix sheet; mesenchymal stem cells; osteogenic differentiation