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Abstract

The efficient healing of critical-sized bone defects using synthetic biomaterial-based strategies is promising but
remains challenging as it requires the development of biomaterials that combine a 3D porous architecture and a
robust biological activity. Bioactive glasses (BGs) are attractive candidates as they stimulate a biological response
that favors osteogenesis and vascularization, but amorphous 3D porous BGs are difficult to produce
because conventional compositions crystallize during processing. Here, we rationally designed a porous,
strontium-releasing, bioactive glass-based scaffold (pSrBG) whose composition was tailored to deliver strontium
and whose properties were optimized to retain an amorphous phase, induce tissue infiltration and encourage
bone formation. The hypothesis was that it would allow the repair of a critical-sized defect in an ovine model
with newly-formed bone exhibiting physiological matrix composition and structural architecture. Histological
and histomorphometric analyses combined with indentation testing showed pSrBG encouraged near perfect
bone-to-material contact and the formation of well-organized lamellar bone. Analysis of bone quality by a
combination of Raman spectral imaging, small-angle X-ray scattering, X-ray fluorescence and focused ion beamscanning
electron microscopy demonstrated that the repaired tissue was akin to that of normal, healthy bone,
and incorporated small amounts of strontium in the newly formed bone mineral. These data show the potential
of pSrBG to induce an efficient repair of critical-sized bone defects and establish the importance of thorough
multi-scale characterization in assessing biomaterial outcomes in large animal models.