Rheological behavior and injectability of PEG/glycerol/bioactive glass-based bone grafts incorporating Denosumab

Abstract

In this study, injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass (BG) incorporated into a carrier system composed of glycerol and polyethylene glycol (PEG) with different average molecular weights. Selected putty samples were further incorporated with varying amounts of Denosumab (5wt%–10wt%) to investigate its influence on rheological behavior and flow properties using mathematical modeling. All PEG/glycerol/45S5-based putty samples exhibited viscoelastic behavior (storage modulus > loss modulus) and pseudoplastic behavior (n < 1), with viscosity values required for optimal flow remaining below 1000 Pa·s. Both viscosity and thixotropic area increased proportionally with higher BG content and smaller-sized BG particles. All putty samples showed more than 98% injectability through a 12G cannula, suggesting potential clinical suitability. However, injectability decreased with smaller cannulas, dropping to 34.7%–58.3% with a 19G cannula and further decreasing with a 23G cannula at higher BG contents. Incorporation of Denosumab preserved viscoelasticity and injectability but modified the flow behavior, shifting it from pseudoplastic to more Newtonian with higher Denosumab content, while also reducing viscosity and thixotropic area values. Among all tested samples, putty containing a lower amount of Denosumab and smaller-sized BG exhibited the most suitable combination of injectability and rheological features. All putty samples were well described by both the Power law and Herschel–Bulkley rheological models (coefficient of determination > 0.95). This study highlights the influence of Denosumab on flowability and rheological relationships and suggests potential improvements in bioactivity through a dual synergistic effect of BG and Denosumab in minimally invasive bone graft systems.

Keywords

bioactive glass / biomaterial / Denosumab / injectable bone graft / injectability / putty / synergetic effect / rheology

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