title: *An Engineered Multiphase Three-Dimensional Microenvironment to Ensure the Controlled Delivery of Cyclic Strain and Human Growth Differentiation Factor 5 for the Tenogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells.
abstract: At present, injuries or rupture of tendons are treated by surgical repair or conservative approaches with unpredictable clinical outcome. Alternative strategies to repair tendon defects without the undesirable side effects associated with the current options are needed. With this in mind, a tissue engineering approach has gained considerable attention as a promising strategy. Here we investigated a synthetic three-dimensional (3D) microenvironment able to interact with stem cells and inducing, via coupled biochemical and physical signals, their early commitment toward the tenogenic lineage. This multiphase 3D construct consisted of a braided hyaluronate elastic band merged with human bone marrow mesenchymal stem cells (hBMSCs) and poly-lactic-co-glycolic acid microcarriers loaded with human growth differentiation factor 5 (hGDF-5) by means of fibrin hydrogel. The multiphase structure allowed hBMSC culture under cyclic strain within a microenvironment where a controlled amount of hGDF-5 was regularly delivered. The cooperative biochemical and physical stimuli induced significantly increased expression of tenogenic markers, such as collagen type I and III, decorin, scleraxis, and tenascin-C, within only 3 days of dynamic hBMSC culture. This approach opens exciting perspectives for future development of engineered tendon tissue substitutes.
authors.affiliation: 1 Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna , Bologna, Italy .
authors.forename: Marco
authors.initials: M
authors.lastname: Govoni
authors.affiliation: 2 Laboratory "Stem Cells" U.O.C. Laboratory of Immunohematology and Transfusion Center , "Spirito Santo" Hospital, Pescara, Italy .
authors.forename: Anna Concetta
authors.initials: AC
authors.lastname: Berardi
authors.affiliation: 1 Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna , Bologna, Italy .|3 Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy .
authors.forename: Claudio
authors.initials: C
authors.lastname: Muscari
authors.affiliation: 4 Department of Industrial Engineering, University of Salerno , Fisciano, Italy .
authors.forename: Roberta
authors.initials: R
authors.lastname: Campardelli
authors.affiliation: 3 Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy .
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonafè
authors.affiliation: 1 Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna , Bologna, Italy .|3 Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna , Bologna, Italy .
authors.forename: Carlo
authors.initials: C
authors.lastname: Guarnieri
authors.affiliation: 4 Department of Industrial Engineering, University of Salerno , Fisciano, Italy .
authors.forename: Ernesto
authors.initials: E
authors.lastname: Reverchon
authors.affiliation: 1 Health Sciences and Technologies-Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna , Bologna, Italy .|5 Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna , Cesena, Italy .|6 Advanced Research Center on Electronic Systems (ARCES), University of Bologna , Bologna, Italy .
authors.forename: Emanuele
authors.initials: E
authors.lastname: Giordano
authors.affiliation: 7 Department of Medicine, Surgery and Dentistry, University of Salerno , Baronissi, Italy .
authors.forename: Nicola
authors.initials: N
authors.lastname: Maffulli
authors.affiliation: 4 Department of Industrial Engineering, University of Salerno , Fisciano, Italy .|7 Department of Medicine, Surgery and Dentistry, University of Salerno , Baronissi, Italy .
authors.forename: Giovanna
authors.initials: G
authors.lastname: Della Porta
mesh_terms: D000328:Adult; D019070:Cell Lineage / Q000187:drug effects; D060833:Cellular Microenvironment; D055119:Elastic Modulus; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008863:Microspheres; D013314:Stress, Mechanical; D013710:Tendons / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5
keywords: PLGA microcarriers; bioactive 3D scaffold; cyclic strain; human bone marrow mesenchymal stem cells; human growth differentiation factor 5