Abstract
Phosphate-based glasses (PBGs) are bioactive and fully degradable materials with tailorable degradation rates. PBGs can be produced as porous microspheres through a single-step process, using changes in their formulation and geometry to produce varying pore sizes and interconnectivity for use in a range of applications, including biomedical use. Calcium phosphate PBGs have recently been proposed as orthobiologics, based on their in vitro cytocompatibility and ion release profile. In this study, porous microspheres made of two PBG formulations either containing TiO2 (P40Ti) or without (P40) were implanted in vivo in a large animal model of bone defect. The biocompatibility and osteogenic potential of these porous materials were assessed 13 weeks postimplantation in sheep and compared to empty defects and autologous bone grafts used as negative and positive controls. Histological analysis showed marked differences between the two formulations, as lower trabeculae-like interconnection and higher fatty bone marrow content were observed in the faster degrading P40-implanted defects, while the slower degrading P40Ti material promoted dense interconnected tissue. Autologous bone marrow concentrate (BMC) was also incorporated within the P40 and P40Ti microspheres in some defects; however, no significant differences were observed in comparison to microspheres implanted alone. Both formulations induced the formation of a collagen-enriched matrix, from 20 to 40% for P40 and P40Ti2.5 groups, suggesting commitment toward the bone lineage. With the faster degrading P40 formulation, mineralization of the tissue matrix was observed both with and without BMC. Some lymphocyte-like cells and foreign body multinucleated giant cells were observed with P40Ti2.5, suggesting that this more durable formulation might be linked to an inflammatory response. In conclusion, these first in vivo results indicate that PBG microspheres could be useful candidates for bone repair and regenerative medicine strategies and highlight the role of material degradation in the process of tissue formation and maturation.
Highlights
Bone grafts, either autologous or allogenic, are currently the gold-standard strategy for the repair of bone defects due to either their intrinsic osteoconductive, osteoinductive, and/or osteointegration capacity
Hydroxyapatite and β-tricalcium phosphate are already used in the clinic, showing osteoconductive properties; their slow degradation rate has been highlighted as a limitation to regeneration.[3]
Two formulations of dehydrated with ethanol and xylene solutions and mounted using porous phosphate-based glasses (PBGs) microspheres were prepared in the system resin mounting solution
Summary
Either autologous or allogenic, are currently the gold-standard strategy for the repair of bone defects due to either their intrinsic osteoconductive, osteoinductive, and/or osteointegration capacity. Hydroxyapatite and β-tricalcium phosphate are already used in the clinic, showing osteoconductive properties; their slow degradation rate has been highlighted as a limitation to regeneration.[3] Bioactive glasses have been developed as biomaterials, including silicabased glasses known as Bioglass. While silica-based glasses are slow degrading materials, phosphate-based glasses (PBGs) have significant potential as they are fully resorbable and display tailorable degradation properties (ranging from days, months to years), including formulation and geometry.[4] The basic constituents of PBGs include P2O5, Na2O, and CaO mimicking the mineral part of the bone in composition, while doping with different oxides such as AgO, CuO, ZnO, MgO, and SrO has been reported to produce specialized glasses for Received: March 14, 2019 Accepted: April 4, 2019 Published: April 16, 2019
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