title: TGFβ2 differentially modulates smooth muscle cell proliferation and migration in electrospun gelatin-fibrinogen constructs.
abstract: A main goal of tissue engineering is the development of scaffolds that replace, restore and improve injured tissue. These scaffolds have to mimic natural tissue, constituted by an extracellular matrix (ECM) support, cells attached to the ECM, and signaling molecules such as growth factors that regulate cell function. In this study we created electrospun flat sheet scaffolds using different compositions of gelatin and fibrinogen. Smooth muscle cells (SMCs) were seeded on the scaffolds, and proliferation and infiltration were evaluated. Additionally, different concentrations of Transforming Growth Factor-beta2 (TGFβ2) were added to the medium with the aim of elucidating its effect on cell proliferation, migration and collagen production. Our results demonstrated that a scaffold with a composition of 80% gelatin-20% fibrinogen is suitable for tissue engineering applications since it promotes cell growth and migration. The addition of TGFβ2 at low concentrations (≤ 1 ng/ml) to the culture medium resulted in an increase in SMC proliferation and scaffold infiltration, and in the reduction of collagen production. In contrast, TGFβ2 at concentrations >1 ng/ml inhibited cell proliferation and migration while stimulating collagen production. According to our results TGFβ2 concentration has a differential effect on SMC function and thus can be used as a biochemical modulator that can be beneficial for tissue engineering applications.
authors.affiliation: Graduate Interdisciplinary Program of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Ardila
authors.affiliation: Graduate Interdisciplinary Program of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Ehab
authors.initials: E
authors.lastname: Tamimi
authors.affiliation: Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Forest L
authors.initials: FL
authors.lastname: Danford
authors.affiliation: Graduate Interdisciplinary Program of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Darren G
authors.initials: DG
authors.lastname: Haskett
authors.affiliation: Center for Bioengineering Innovation, Northern Arizona University, Flagstaff, AZ 86011, USA; Department of Mechanical Engineering, Northern Arizona University, Flagstaff, AZ 86011, USA; Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ 86011, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kellar
authors.affiliation: Department of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85721, USA; Sarver Heart Center, The University of Arizona, Tucson, AZ 85724, USA; BIO5 Institute for Biocollaborative Research, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Doetschman
authors.affiliation: Graduate Interdisciplinary Program of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721, USA; Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, AZ 85721, USA; BIO5 Institute for Biocollaborative Research, The University of Arizona, Tucson, AZ 85721, USA; Department of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721, USA. Electronic address: jpv1@email.arizona.edu.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Vande Geest
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005340:Fibrinogen / Q000494:pharmacology*; D005780:Gelatin / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D034421:Sus scrofa; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology*; D000096985:Calponins
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D005340:Fibrinogen; D005780:Gelatin; D008840:Microfilament Proteins; D053781:Transforming Growth Factor beta2; D000096985:Calponins
keywords: Electrospinning; Migration; Non-synthetic biopolymers; Proliferation; Smooth muscle cells; TGFB2