title: Combined delivery of FGF-2, TGF-β1, and adipose-derived stem cells from an engineered periosteum to a critical-sized mouse femur defect.
abstract: Critical-sized long bone defects suffer from complications including impaired healing and non-union due to substandard healing and integration of devitalized bone allograft. Removal of the periosteum contributes to the limited healing of bone allografts. Restoring a periosteum on bone allografts may provide improved allograft healing and integration. This article reports a polysaccharide-based tissue engineered periosteum that delivers basic fibroblast growth factor (FGF-2), transforming growth factor-β1 (TGF-β1), and adipose-derived mesenchymal stem cells (ASCs) to a critical-sized mouse femur defect. The tissue engineered periosteum was evaluated for improving bone allograft healing and incorporation by locally delivering FGF-2, TGF-β1, and supporting ASCs transplantation. ASCs were successfully delivered and longitudinally tracked at the defect site for at least 7 days post operation with delivered FGF-2 and TGF-β1 showing a mitogenic effect on the ASCs. At 6 weeks post implantation, data showed a non-significant increase in normalized bone callus volume. However, union ratio analysis showed a significant inhibition in allograft incorporation, confirmed by histological analysis, due to loosening of the nanofiber coating from the allograft surface. Ultimately, this investigation shows our tissue engineered periosteum can deliver FGF-2, TGF-β1, and ASCs to a mouse critical-sized femur defect and further optimization may yield improved bone allograft healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 900-911, 2017.
authors.affiliation: School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Raimundo
authors.initials: R
authors.lastname: Romero
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: John K
authors.initials: JK
authors.lastname: Travers
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Emilie
authors.initials: E
authors.lastname: Asbury
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Attie
authors.initials: A
authors.lastname: Pennybaker
authors.affiliation: Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Laura
authors.initials: L
authors.lastname: Chubb
authors.affiliation: Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Ruth
authors.initials: R
authors.lastname: Rose
authors.affiliation: School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, 80523.|Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Ehrhart
authors.affiliation: School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, 80523.|Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Kipper
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D064591:Allografts; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005269:Femur / Q000293:injuries / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010521:Periosteum / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods; D053773:Transforming Growth Factor beta1 / Q000737:chemistry / Q000494:pharmacology
chemical_list: C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2
keywords: bone allograft; chitosan nanofibers; heparin-binding growth factors; mesenchymal stem cell; tissue-engineered periosteum