Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass

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.

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

“…117 With the ongoing development of bone TE, modifications of biomaterial scaffolds with chemical groups or controlled growth factors could overwhelmingly enhance their physicochemical properties and endow them with satisfying biofunctions. 117 Biomaterials have been optimized by incorporating additional chemical groups 118 or bioactive factors, 119 as well as by releasing certain growth factors, 120 ions, 121 and other novel active small molecules. To this end, there is increasing research on modifying the surface architecture and chemical components of 3D biomaterial scaffolds to enhance cell adhesion, growth, differentiation, and migration, and consequently bone regeneration.…”

“…This novel magnetic construct is highly promising for bone regeneration, especially γIONP-CPC, because the internalized magnetic γIONPs inside the cell membrane reoriented and distorted, resulting in an alteration of the cell cycles and differentiation. Additionally, some metal ions such as calcium (Ca), magnesium (Mg), 132,133 strontium (Sr), 121 and copper (Cu) 134 , which mediate chemobiological homeostasis of human, are widely applied in chemical modifications on bone substitute scaffolds to stimulate the osteogenesis and angiogenesis. Minardi et al added Mg to the HA/Col I composite and showed that cells seeded in vivo in the scaffold retained high viability and reproducibility for mature cortical bone formation.…”

“…Autefage et al designed a porous scaffold to achieve controlled release of Sr, which induced tissue infiltration and encouraged bone formation. 121 Recently, osteoimmunomodulation is getting more and more attention in bone TE, as a favorable osteoimmune microenvironment plays a vital role in successful biomaterials-mediated bone regeneration. The controlled release of certain metal ions from scaffolds, such as Zinc, Mg and Sr, could orchestrate osteogenesis by modulating the local immune microenvironment.…”

Nanocellulose/bioactive glass cryogels as scaffolds for bone regeneration

“…22 Here, we propose cellulose nanofibrils (CNF), which effectively form networks in composites, to form porous macrostructures that are able to grow and regenerate bone by the addition of bioactive glass. 23,24 Thus, the high mechanical performance of the cellulose nanostructures is combined with the bioactivity of the mineral component (containing SiO 2 , CaO, Na 2 O, and P 2 O) to form an advanced biomedical composite. This strategy overcomes the two main obstacles found in the individual use of these materials for bone tissue engineering, namely, the absence of bioactivity in nanocellulose and the brittleness of the bioactive glass and the challenges it poses in manufacturing complex structures.…”

Complementary techniques to analyse pericellular matrix formation by human MSC within hyaluronic acid hydrogels

“…or other components of the ECM (sugars, e.g.). Raman spectroscopy is an unsupervised, label-free technique based on the inelastic scattering of monochromatic light that has been used extensively to identify the biochemical fingerprint of cells, 13 tissues 14,15 and ECM formed by cells in culture. [16][17][18][19] Raman spectroscopy can be utilised with no additional labelling as a 3D confocal imaging technique, and whilst not capable of specifically identifying biological species, can distinguish between proteins, lipids, and nucleic acids, amongst other biologics.…”