title: A nano-hydroxyapatite--pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering.
abstract: Research in bone tissue engineering is focused on the development of alternatives to allogenic and autologous bone grafts that can stimulate bone healing. Here, we present scaffolds composed of the natural hydrophilic polysaccharides pullulan and dextran, supplemented or not with nanocrystalline hydroxyapatite particles (nHA). In vitro studies revealed that these matrices induced the formation of multicellular aggregates and expression of early and late bone specific markers with human bone marrow stromal cells in medium deprived of osteoinductive factors. In absence of any seeded cells, heterotopic implantation in mice and goat, revealed that only the composite macroporous scaffold (Matrix + nHA) (i) retained subcutaneously local growth factors, including Bone Morphogenetic Protein 2 (BMP2) and VEGF165, (ii) induced the deposition of a biological apatite layer, (iii) favored the formation of a dense mineralized tissue subcutaneously in mice, as well osteoid tissue after intramuscular implantation in goat. The composite scaffold was thereafter implanted in orthotopic preclinical models of critical size defects, in small and large animals, in three different bony sites, i.e. the femoral condyle of rat, a transversal mandibular defect and a tibial osteotomy in goat. The Matrix + nHA induced a highly mineralized tissue in the three models whatever the site of implantation, as well as osteoid tissue and bone tissue regeneration in direct contact to the matrix. We therefore propose this composite matrix as a material for stimulating bone cell differentiation of host mesenchymal stem cells and bone formation for orthopedic and maxillofacial surgical applications.
authors: Inserm U1026, University Bordeaux Segalen, Tissue Bioengineering, F-33076 Bordeaux, France.
authors: Jean Christophe
authors: JC
authors: Fricain
authors: Silke
authors: S
authors: Schlaubitz
authors: Catherine
authors: C
authors: Le Visage
authors: Isabelle
authors: I
authors: Arnault
authors: Sidi Mohammed
authors: SM
authors: Derkaoui
authors: Robin
authors: R
authors: Siadous
authors: Sylvain
authors: S
authors: Catros
authors: Charlotte
authors: C
authors: Lalande
authors: Reine
authors: R
authors: Bareille
authors: Martine
authors: M
authors: Renard
authors: Thierry
authors: T
authors: Fabre
authors: Sandro
authors: S
authors: Cornet
authors: Marlène
authors: M
authors: Durand
authors: Alain
authors: A
authors: Léonard
authors: Nouredine
authors: N
authors: Sahraoui
authors: Didier
authors: D
authors: Letourneur
authors: Joëlle
authors: J
authors: Amédée
mesh_terms: D001483:Base Sequence; D001672:Biocompatible Materials; D001842:Bone and Bones; D002478:Cells, Cultured; D017931:DNA Primers; D003911:Dextrans / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D005936:Glucans / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011134:Polysaccharides / Q000737:chemistry*; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D017931:DNA Primers; D003911:Dextrans; D005936:Glucans; D011134:Polysaccharides; C009109:pullulan; D017886:Durapatite