Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep

Abstract

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting.In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels.Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis.

The Influence of Nanometals, Dispersed in the Electrophoretic Nanohydroxyapatite Coatings on the Ti13Zr13Nb Alloy, on Their Morphology and Mechanical Properties

“…Numerous attempts for this type of HAp coating doping have been reported. The doping elements, including Zn [26][27][28][29][30][31][32], Mg [10,33], Zn/Mg [34], Fe [35], Sr [36], Sr/Mn [37], Sr/Cu [16], La/Cu [15], Ce [38,39], Si [40,41] were proposed to increase the mechanical strength of HAp/nanoHAp coatings. Moreover, the additions to HAp of oxides like ZnO, SiO 2 , MgO and Ag 2 O [42,43], and TiO 2 [44][45][46], carbon nanotubes (CNTs) [27,47,48], quercetin [49], and aptamer [50] were also investigated.…”

Rubidium doped nano-hydroxyapatite with cytocompatibility and antibacterial

“…Therefore, many multidisciplinary research groups directed their scientific interests toward inorganic antibacterial elements for endowing biomaterials with antibacterial capacity [14,15]. Various kinds of elements such as magnesium [16][17][18], strontium [18,19], silicon [20], zinc [21], lithium [22] and iron [23] have been used as doping elements, which can promote the proliferation and differentiation of osteoblasts. But only limited elements have antibacterial effect, such as silver, copper and zinc.…”

Effects of Ipriflavone-Loaded Mesoporous Nanospheres on the Differentiation of Endothelial Progenitor Cells and Their Modulation by Macrophages

“…EPCs are considered a promising cell strategy for tissue engineering applications due to their highly proliferative and antithrombogenic behavior [ 41 , 42 ]. This cell type can be easily obtained from peripheral blood [ 26 , 27 ], and it is very appropriate as an in vitro experimental model for the study of the angiogenic potential of different biomaterials [ 19 , 21 , 43 , 44 ]. In this work, after isolating EPCs from porcine peripheral blood and culturing for 23 and 30 days in EGM-2 differentiation medium, the expression of CD31, CD34, VEGFR2, eNOS, and vWF, as endothelial phenotype markers, was analyzed by flow cytometry.…”

“…Thus, osteogenesis is a process coupled to vascularization during bone development and growth [ 17 ]. For this reason, angiogenic biomaterials are designed to promote vascularization and optimize bone regeneration [ 18 , 19 , 20 , 21 ]. In this context, nanoparticles of bioactive materials loaded with different drugs represent an interesting strategy to promote bone regeneration by stimulating osteogenesis and angiogenesis and inhibiting bone resorption [ 22 , 23 ].…”