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Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs
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
Health Unit, INASMET-Tecnalia, San Sebastian E-20009, Spain
Materials Engineering Centre, UdR INSTM, NIPLAB, University of Perugia, Terni 05100, Italy
Department of Biomaterials, Radboud University, Nijmegen Medical Centre, Nijmegen 6525 GA, The Netherlands
* Author to whom correspondence should be addressed.
Received: 27 December 2011; in revised form: 13 February 2012 / Accepted: 14 February 2012 / Published: 22 February 2012
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.
Keywords: bone tissue engineering; biomimetic nanocomposites; mesenchymal stem cell
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Ciapetti, G.; Granchi, D.; Devescovi, V.; Baglio, S.R.; Leonardi, E.; Martini, D.; Jurado, M.J.; Olalde, B.; Armentano, I.; Kenny, J.M.; Walboomers, F.X.; Alava, J.I.; Baldini, N. Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs. Int. J. Mol. Sci. 2012, 13, 2439-2458.
Ciapetti G, Granchi D, Devescovi V, Baglio SR, Leonardi E, Martini D, Jurado MJ, Olalde B, Armentano I, Kenny JM, Walboomers FX, Alava JI, Baldini N. Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs. International Journal of Molecular Sciences. 2012; 13(2):2439-2458.
Ciapetti, Gabriela; Granchi, Donatella; Devescovi, Valentina; Baglio, Serena R.; Leonardi, Elisa; Martini, Desirèe; Jurado, Maria Jesus; Olalde, Beatriz; Armentano, Ilaria; Kenny, Josè M.; Walboomers, Frank X.; Alava, Josè Inaki; Baldini, Nicola. 2012. "Enhancing Osteoconduction of PLLA-Based Nanocomposite Scaffolds for Bone Regeneration Using Different Biomimetic Signals to MSCs." Int. J. Mol. Sci. 13, no. 2: 2439-2458.