Porous phosphate-based glass microspheres show biocompatibility, tissue infiltration and osteogenic onset in an ovine bone defect model

McLaren, Jane S.; Macri-Pellizzeri, Laura; Zakir Hossain, Kazi M.; Patel, Uresha; Grant, David M.; Scammell, Brigitte E.; Ahmed, Ifty; Sottile, Virginie

Abstract

Phosphate-based glasses (PBG) 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 PBG 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 post-implantation 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, whilst 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 towards the bone lineage. With the faster degrading P40 formulation, mineralisation 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 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.

Citation

McLaren, J. S., Macri-Pellizzeri, L., Zakir Hossain, K. M., Patel, U., Grant, D. M., Scammell, B. E., Ahmed, I., & Sottile, V. (2019). Porous phosphate-based glass microspheres show biocompatibility, tissue infiltration and osteogenic onset in an ovine bone defect model. ACS Applied Materials and Interfaces, 11(17), 15436–15446. https://doi.org/10.1021/acsami.9b04603

• Journal Article Type: Article
• Acceptance Date: Apr 2, 2019
• Online Publication Date: Apr 16, 2019
• Publication Date: Apr 16, 2019
• Deposit Date: Apr 12, 2019
• Publicly Available Date: May 13, 2019
• Journal: ACS Applied Materials and Interfaces
• Print ISSN: 1944-8244
• Electronic ISSN: 1944-8252
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 17
• Pages: 15436–15446
• DOI: https://doi.org/10.1021/acsami.9b04603
• Keywords: Phosphate-based glasses, Porous microspheres, Tissue engineering, In vivo bone defect, Bone regeneration
• Public URL: https://nottingham-repository.worktribe.com/output/1782709
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsami.9b04603
• Contract Date: Apr 12, 2019