title: Rheological properties, biocompatibility and in vivo performance of new hydrogel-based bone fillers.
abstract: Three different heterologous substitutes for bone regeneration, manufactured with equine-derived cortical powder (CP), cancellous chips (CC) and demineralized bone matrix granules (DBM), were compared in in vitro and in vivo settings. We tested: a commercially available bone paste (Osteoplant-Activagen™, consisting of aqueous collagenous carrier, CP, DBM; named A); a second-generation injectable paste (20 kDa polyethylene glycol/hydroxypropyl-methyl cellulose-based hydrogel, CP, DBM; B); a pre-formed bone filler (400 kDa polyethylene oxide/hydroxypropyl-methyl cellulose-based hydrogel, CP, CC, DBM; C). Vitamin C acted as a visco-modulator during C and B β-rays sterilization, modifying graft injectability. For each filler, we examined dissolution in culture medium, gene expression of the substitute-exposed osteogenically-induced human bone marrow stromal cells (hBMSC), and performance in a rabbit bone defect model. A dissolved after 1 h, while fragmentation of B peaked after 8 h. C remained unaltered for 2 days, but affected the microenvironmental pH, slowing the proliferation of exposed cells. B-exposed hBMSC overexpressed bone sialoprotein, osteocalcin and RUNX2. For all fillers histological results evidenced bridged lesion margins, marrow replenishment and bone-remodeling. However, B-treated lesions displayed a metachromatic type II collagen-rich matrix with prehypertrophic-like cells, matching the in vitro expression of cartilage-specific markers, and suggesting a possible application of B/C double-layer monolithic osteochondral plugs for full-thickness articular defects.
authors.affiliation: Stem Cell Laboratory, Dept. of Experimental Medicine, University of Genova, c/o Advanced Biotechnology Centre, L.go R. Benzi, 10, 16132-Genova, Italy. paolo.giannoni@unige.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giannoni
authors.forename: Federico
authors.initials: F
authors.lastname: Villa
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cordazzo
authors.forename: Luciano
authors.initials: L
authors.lastname: Zardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Fattori
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Quarto
authors.forename: Mauro
authors.initials: M
authors.lastname: Fiorini
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000293:injuries; D002460:Cell Line; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D059630:Mesenchymal Stem Cells; D011817:Rabbits; D012212:Rheology
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate