title: Human Adipose Stem Cells Differentiated on Braided Polylactide Scaffolds Is a Potential Approach for Tendon Tissue Engineering.
abstract: Growing number of musculoskeletal defects increases the demand for engineered tendon. Our aim was to find an efficient strategy to produce tendon-like matrix in vitro. To allow efficient differentiation of human adipose stem cells (hASCs) toward tendon tissue, we tested different medium compositions, biomaterials, and scaffold structures in preliminary tests. This is the first study to report that medium supplementation with 50 ng/mL of growth and differentiation factor-5 (GDF-5) and 280 μM l-ascorbic acid are essential for tenogenic differentiation of hASCs. Tenogenic medium (TM) was shown to significantly enhance tendon-like matrix production of hASCs compared to other tested media groups. Cell adhesion, proliferation, and tenogenic differentiation of hASCs were supported on braided poly(l/d)lactide (PLA) 96l/4d copolymer filament scaffolds in TM condition compared to foamed poly(l-lactide-co-ɛ-caprolactone) (PLCL) 70L/30CL scaffolds. A uniform cell layer formed on braided PLA 96/4 scaffolds when hASCs were cultured in TM compared to maintenance medium (MM) condition after 14 days of culture. Furthermore, total collagen content and gene expression of tenogenic marker genes were significantly higher in TM condition after 2 weeks of culture. The elastic modulus of PLA 96/4 scaffold was more similar to the elastic modulus reported for native Achilles tendon. Our study showed that the optimized TM is needed for efficient and rapid in vitro tenogenic extracellular matrix production of hASCs. PLA 96/4 scaffolds together with TM significantly stimulated hASCs, thus demonstrating the potential clinical relevance of this novel and emerging approach to tendon injury treatments in the future.
authors.affiliation: 1 Adult Stem Cells, BioMediTech, University of Tampere , Tampere, Finland .|2 Science Center, Tampere University Hospital , Tampere, Finland .
authors.forename: Kaisa
authors.initials: K
authors.lastname: Vuornos
authors.affiliation: 1 Adult Stem Cells, BioMediTech, University of Tampere , Tampere, Finland .|2 Science Center, Tampere University Hospital , Tampere, Finland .
authors.forename: Miina
authors.initials: M
authors.lastname: Björninen
authors.affiliation: 3 Department of Electronics and Communications Engineering, BioMediTech, Tampere University of Technology , Tampere, Finland .
authors.forename: Elina
authors.initials: E
authors.lastname: Talvitie
authors.affiliation: 3 Department of Electronics and Communications Engineering, BioMediTech, Tampere University of Technology , Tampere, Finland .
authors.forename: Kaarlo
authors.initials: K
authors.lastname: Paakinaho
authors.affiliation: 3 Department of Electronics and Communications Engineering, BioMediTech, Tampere University of Technology , Tampere, Finland .
authors.forename: Minna
authors.initials: M
authors.lastname: Kellomäki
authors.affiliation: 4 Tampere School of Health Sciences, University of Tampere , Tampere, Finland .
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.affiliation: 1 Adult Stem Cells, BioMediTech, University of Tampere , Tampere, Finland .|2 Science Center, Tampere University Hospital , Tampere, Finland .
authors.forename: Susanna
authors.initials: S
authors.lastname: Miettinen
authors.affiliation: 5 Department of Oral and Maxillofacial Sciences, Clinicum, Faculty of Medicine, University of Helsinki , Helsinki, Finland .|6 Department of Oral and Maxillofacial Diseases, Head and Neck Center, Helsinki University Hospital , Helsinki, Finland .
authors.forename: Riitta
authors.initials: R
authors.lastname: Seppänen-Kaijansinkko
authors.affiliation: 5 Department of Oral and Maxillofacial Sciences, Clinicum, Faculty of Medicine, University of Helsinki , Helsinki, Finland .|7 Department of Biomaterials Science and Technology, University of Twente , Enschede, The Netherlands .
authors.forename: Suvi
authors.initials: S
authors.lastname: Haimi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011091:Polyesters / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013710:Tendons / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D003470:Culture Media; D011091:Polyesters; C033616:poly(lactide); D003094:Collagen