<p>Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3&beta; pathway and facilitate bone repair in vivo</p>

Abstract

BackgroundBiomaterial-induced osteogenesis is mainly related to hierarchically porous structures and bioactive components. Rare earth elements are well known to promote osteogenesis and stimulate bone repair; however, the underlying biological effects of gadolinium (Gd) element on bone regeneration are not yet known.MethodsIn this study, we successfully fabricated gadolinium-doped bioglass (Gd-BG) scaffolds by combining hollow mesoporous Gd-BG microspheres with chitosan and evaluated in vitro effects and underlying mechanisms with Cell Counting Kit-8, scanning electron microscopy, alkaline phosphatase, Alizarin red staining, and polymerase chain reaction. Cranial defect model of rats was constructed to evaluate their in vivo effects.ResultsThe results indicated that Gd-BG scaffolds could promote the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Mechanistically, the Akt/GSK3β signaling pathway was activated by the Gd-BG scaffolds. The enhancing effect of Gd-BG scaffolds on the osteogenic differentiation of hBMSCs was inhibited by the addition of LY294002, an inhibitor of Akt. Moreover, the in vivo cranial defect model of rats indicated that the Gd-BG scaffolds could effectively promote bone regeneration.ConclusionBoth in vitro and in vivo results suggested that Gd-BG scaffolds have promising applications in bone tissue engineering.

<p>Lanthanides-Substituted Hydroxyapatite/<em>Aloe vera</em> Composite Coated Titanium Plate for Bone Tissue Regeneration</p>

“…Moreover, the invivo results show that bone regeneration ability was higher for Gd doped BG than undoped BG. 39 For this reason, the trivalent lanthanide ion Gd 3+ was added along with these minerals on the HAP matrix.…”

Holmium-Containing Bioactive Glasses Dispersed in Poloxamer 407 Hydrogel as a Theragenerative Composite for Bone Cancer Treatment

“…Rare-earth ions, including Ho 3+ , have ionic radii similar to Ca 2+ , acting either as agonist or antagonist of Ca 2+ sites in biochemical pathways, and can stimulate pre-osteoblastic cell proliferation [ 71 ]. Recently, Zhu et al [ 72 ] showed that Gd 3+ ions leached from bioactive glasses could stimulate protein expression related to the Wnt signaling pathway, which is related to osteogenic differentiation of human bone marrow-derived mesenchymal stem cell. In this mechanism, Gd 3+ ions would be related to increased expression of protein kinase B (Akt) and glycogen synthase kinase β (GSK3β), which together form the Akt/GSK3β pathway.…”

In Vivo Behavior of Bioactive Glass-Based Hybrids in Animal Models For Bone Regeneration

“…Compared to melt-derived compositions, where sol-gel derived compositions offer considerable freedom in process parameters, mesoporous glasses provide porosities for drug loading and controlled local delivery [67]. Coupled with a wide range of fabrication methods and processes, where freeze-drying is rapidly evolving into the method of choice owing to its simplicity and the geometrical flexibility [27,28,33,38,40,45,72]. Certain strategies appear more promising: For example, scaffolds seeded with MSCs that secrete B2BMP7, allowing for cells, the implanted scaffold, and secreted growth factors functioning synergistically in tissue regeneration [70].…”

“…In comparison, freeze-dried scaffolds of sol-gel derived, gadolinium-doped bioactive glass microspheres and chitosan have also been demonstrated to promote osteogenesis in calvarial defects in Sprague-Dawley rats. At 8 weeks post-implantation, significant increases in both new bone volume and bone mineral density are observed compared to equivalent scaffolds containing gadolinium-free bioactive glass [27].…”