title: Incorporation of nanostructured hydroxyapatite and poly(N-isopropylacrylamide) in demineralized bone matrix enhances osteoblast and human mesenchymal stem cell activity.
abstract: Demineralized bone matrix (DBM) is currently used in many clinical applications for bone augmentation and repair. DBM is normally characterized by the presence of bone morphogenetic proteins. In this study, the authors have optimized methods to obtain DBM under good manufacturing practice, resulting in enhanced bioactivity. The processed DBM can be used alone, together with nanostructured hydroxyapatite (nanoHA), or dispersed in a physiological carrier or hydrogel. In this study, osteoblasts (MG-63) and human bone marrow derived mesenchymal stem cells (hMSCs) were cultured on DBM pastes made in phosphate buffered saline solution or poly(N-isopropylacrylamide) (PNIPAAM) hydrogels with or without nanoHA. The authors observed that the presence of PNIPAAM reduced osteoblast adhesion, while the addition of nanoHA increased osteoblast adhesion, proliferation, interleukin-6 (IL-6) production, and reduced lactate dehydrogenase (LDH) production. Increasing concentrations of PNIPAAM in combination with nanoHA further increased osteoblast proliferation, and decreased IL-6 and LDH production. Incorporation of PNIPAAM in DBM enhanced hMSCs proliferation and collagen type-I production. Furthermore, a combination of PNIPAAM and nanoHA further increased alkaline phosphatase and osteocalcin production in hMSCs, independently from the concentration of PNIPAAM. This study shows that combinations of DBM with nanoHA and PNIPAAM seem to offer a promising route to enhance cell activity and induce osteogenic differentiation.
authors.affiliation: Fin-ceramica Faenza S.p.A., Via Ravegnana 186, 48018 Faenza, Ravenna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nicoletti
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy and Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department Rizzoli RIT, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Torricelli
authors.affiliation: Dipartimento di Chimica "G. Ciamician," Università di Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Bigi
authors.affiliation: Banca del Tessuto Muscoloscheletrico, Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136 Bologna, Italy.
authors.forename: Piermaria
authors.initials: P
authors.lastname: Fornasari
authors.affiliation: Laboratory of Preclinical and Surgical Studies, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy and Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Department Rizzoli RIT, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Fini
authors.affiliation: Banca del Tessuto Muscoloscheletrico, Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136 Bologna, Italy and MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, Maastricht 6229ER, The Netherlands.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
mesh_terms: D000180:Acrylic Resins / Q000378:metabolism*; D001672:Biocompatible Materials / Q000378:metabolism; D001857:Bone Matrix / Q000378:metabolism*; D001861:Bone Regeneration; D002448:Cell Adhesion; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D017886:Durapatite / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D049329:Nanostructures / Q000737:chemistry*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; C508600:IL6 protein, human; D015850:Interleukin-6; C052970:poly-N-isopropylacrylamide; D003094:Collagen; D017886:Durapatite