title: Enhancing osteoconduction of PLLA-based nanocomposite scaffolds for bone regeneration using different biomimetic signals to MSCs.
abstract: In bone engineering, the adhesion, proliferation and differentiation of mesenchymal stromal cells rely on signaling from chemico-physical structure of the substrate, therefore prompting the design of mimetic "extracellular matrix"-like scaffolds. In this study, three-dimensional porous poly-L-lactic acid (PLLA)-based scaffolds have been mixed with different components, including single walled carbon nanotubes (CNT), micro-hydroxyapatite particles (HA), and BMP2, and treated with plasma (PT), to obtain four different nanocomposites: PLLA + CNT, PLLA + CNTHA, PLLA + CNT + HA + BMP2 and PLLA + CNT + HA + PT. Adult bone marrow mesenchymal stromal cells (MSCs) were derived from the femur of orthopaedic patients, seeded on the scaffolds and cultured under osteogenic induction up to differentiation and mineralization. The release of specific metabolites and temporal gene expression profiles of marrow-derived osteoprogenitors were analyzed at definite time points, relevant to in vitro culture as well as in vivo differentiation. As a result, the role of the different biomimetic components added to the PLLA matrix was deciphered, with BMP2-added scaffolds showing the highest biomimetic activity on cells differentiating to mature osteoblasts. The modification of a polymeric scaffold with reinforcing components which also work as biomimetic cues for cells can effectively direct osteoprogenitor cells differentiation, so as to shorten the time required for mineralization.
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto OrtopedicoRizzoli, Bologna 40136, Italy.
authors.forename: Gabriela
authors.identifier: 0000-0001-6740-0357
authors.initials: G
authors.lastname: Ciapetti
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto OrtopedicoRizzoli, Bologna 40136, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto OrtopedicoRizzoli, Bologna 40136, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Devescovi
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto OrtopedicoRizzoli, Bologna 40136, Italy.
authors.forename: Serena R
authors.initials: SR
authors.lastname: Baglio
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto OrtopedicoRizzoli, Bologna 40136, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Leonardi
authors.affiliation: Dipartimento di Scienze Anatomiche e dell'Apparato Locomotore, University of Bologna, Bologna 40136, Italy.
authors.forename: Desirèe
authors.initials: D
authors.lastname: Martini
authors.affiliation: Health Unit, INASMET-Tecnalia, San Sebastian E-20009, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Jurado
authors.affiliation: Health Unit, INASMET-Tecnalia, San Sebastian E-20009, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Olalde
authors.affiliation: Materials Engineering Centre, UdR INSTM, NIPLAB, University of Perugia, Terni 05100, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Armentano
authors.affiliation: Materials Engineering Centre, UdR INSTM, NIPLAB, University of Perugia, Terni 05100, Italy.
authors.forename: Josè M
authors.initials: JM
authors.lastname: Kenny
authors.affiliation: Department of Biomaterials, Radboud University, Nijmegen Medical Centre, Nijmegen 6525 GA, The Netherlands.
authors.forename: Frank X
authors.initials: FX
authors.lastname: Walboomers
authors.affiliation: Health Unit, INASMET-Tecnalia, San Sebastian E-20009, Spain.
authors.forename: Josè Inaki
authors.initials: JI
authors.lastname: Alava
authors.affiliation: Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine, Istituto OrtopedicoRizzoli, Bologna 40136, Italy.|Dipartimento di Scienze Anatomiche e dell'Apparato Locomotore, University of Bologna, Bologna 40136, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
mesh_terms: D000368:Aged; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D048091:Guided Tissue Regeneration / Q000295:instrumentation / Q000379:methods; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D053761:Nanocomposites / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D011091:Polyesters; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)