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 beam-scanning 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.
Highlights
Biomaterial-based approaches are an attractive alternative for the repair of substantial bone defects that do not undergo full endogenous repair and have given rise to a lucrative market in regenerative materials [1]
Following reports demonstrating the efficacy of the anti-osteoporosis drug strontium ranelate (SrRan) [9,10], strontium has been incorporated into Bioactive glasses (BGs) for bone repair, as BG's amorphous nature allows it to deliver strontium at a sustained rate
We examined the quality of the newly-formed bone using a combination of materials-based characterization techniques including scanning electron microscopy (SEM) imaging of focused ion beam-milled sections (FIB-SEM), small-angle X-ray scattering (SAXS) and Raman spectroscopy
Summary
Biomaterial-based approaches are an attractive alternative for the repair of substantial bone defects that do not undergo full endogenous repair and have given rise to a lucrative market in regenerative materials [1]. Synthetic inorganic materials including bioactive glasses (BGs) and calcium phosphate ceramics [2,3,4] are attractive because they encourage bone bonding. BGs have the benefit that they can deliver active ions that alter cell responses and stimulate bone regeneration [5,6,7]. As the material degrades, it releases ions including calcium, phosphate, and soluble silica species, which stimulate cellular responses such as bone formation and vascularization [5,6,7]. Strontium-substituted BGs increased the anabolic and anti-catabolic activity of osteoblasts and osteoclasts, respectively [11,12,13], and strontium-substituted materials showed enhanced bone formation and osteointegration in vivo [14,15,16,17,18,19,20]
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