title: Ectopic bone formation using an injectable biphasic calcium phosphate/Si-HPMC hydrogel composite loaded with undifferentiated bone marrow stromal cells.
abstract: We have used a new synthetic injectable composite constituted of hydroxyapatite/tricalcium phosphate (HA/TCP) particles in suspension in a self-hardening Si-hydroxypropylmethylcellulose (HPMC) hydrogel. The aim of this study was to evaluate in vivo the biocompatibility and the new bone formation efficacy of this scaffold loaded with undifferentiated bone marrow stromal cells (BMSCs). This biomaterial was mixed extemporaneously with BMSCs prepared from C57BL/6 mice, injected in subcutaneous and intramuscular sites and retrieved 4 and 8 weeks after implantation. Dissection of the implants revealed a hard consistency and the absence of a fibrous capsule reflecting a good integration into the host tissues. Histological analysis showed mineralized woven bone in the granule inter-space with numerous active osteoclasts attached to the particles as assessed by the presence of multinucleated cells positively stained for TRAP activity and for the a3 subunit of the V-ATPase. Small vessels were homogenously distributed in the whole implants. Similar results were obtained in SC and IM sites and no bone formation was observed in the control groups when cell-free and particle-free transplants were injected. These results indicate that this injectable biphasic calcium phosphate-hydrogel composite mixed with undifferentiated BMSCs is a new promising osteoinductive bone substitute. It also provides with an original in vivo model of osteoclast differentiation and function.
authors.affiliation: CNRS/UNSA FRE 2720, IFR50, Faculté de Médecine, Avenue de Valombrose, and Service de Chirurgie Orthopédique, Hôpital l'Archet 2, Centre Hospitalier Universitaire de Nice, 151 route Saint Antoine de Ginestière, 06202 Nice, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Trojani
authors.forename: Florian
authors.initials: F
authors.lastname: Boukhechba
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Scimeca
authors.forename: Fanny
authors.initials: F
authors.lastname: Vandenbos
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.forename: Guy
authors.initials: G
authors.lastname: Daculsi
authors.forename: Pascal
authors.initials: P
authors.lastname: Boileau
authors.forename: Pierre
authors.initials: P
authors.lastname: Weiss
authors.forename: Georges F
authors.initials: GF
authors.lastname: Carle
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rochet
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D018786:Bone Substitutes / Q000737:chemistry; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D017690:Cell Transplantation; D002474:Cell-Free System / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007150:Immunohistochemistry; D007785:Lactose / Q000031:analogs & derivatives / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology*; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; C509290:hydroxypropylmethylcellulose-lactose matrix; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C020243:calcium phosphate; D025262:Vacuolar Proton-Translocating ATPases; D007785:Lactose; C018392:tricalcium phosphate