45S5-Bioglass^®-Based 3D-Scaffolds Seeded with Human Adipose Tissue-Derived Stem Cells Induce In Vivo Vascularization in the CAM Angiogenesis Assay

Abstract

Poor vascularization is the key limitation for long-term acceptance of large three-dimensional (3D) tissue engineering constructs in regenerative medicine. 45S5 Bioglass Ò was investigated given its potential for applications in bone engineering. Since native Bioglass Ò shows insufficient angiogenic properties, we used a collagen coating, to seed human adipose tissue-derived stem cells (hASC) confluently onto 3D 45S5 Bioglass Ò -based scaffolds. To investigate vascularization by semiquantitative analyses, these biofunctionalized scaffolds were then subjected to in vitro human umbilical vein endothelial cells formation assays, and were also investigated in the chorioallantoic membrane (CAM) angiogenesis model, an in vivo angiogenesis assay, which uses the CAM of the hen's egg. In their native, nonbiofunctionalized state, neither Bioglass Ò -based nor biologically inert fibrous polypropylene control scaffolds showed angiogenic properties. However, significant vascularization was induced by hASC-seeded scaffolds (Bioglass Ò and polypropylene) in the CAM angiogenesis assay. Biofunctionalized scaffolds also showed enhanced tube lengths, compared to unmodified scaffolds or constructs seeded with fibroblasts. In case of biologically inert hernia meshes, the quantification of vascular endothelial growth factor secretion as the key angiogenic stimulus strongly correlated to the tube lengths and vessel numbers in all models. This correlation proved the CAM angiogenesis assay to be a suitable semiquantitative tool to characterize angiogenic effects of larger 3D implants. In addition, our results suggest that combinations of suitable scaffold materials, such as 45S5 Bioglass Ò , with hASC could be a promising approach for future tissue engineering applications.

45S5 Bioglass porous scaffolds: structure, composition and bioactivity characterization

“…The BGs1:3 sample whose heat treatment was performed up to 700 °C exhibited smooth surfaces and a high dispersion, different to another samples; like the BG1:12 where it can be seen joints formation between spheres after sintering, plus some hollow spheres which collapsed after heat treatment and the same BGs1:3 system generating a coral type structure with a certain level of surface roughness. This set of results corresponds with other works, where the bioglass sintering behavior make particle fusion as common, besides the surface roughness loss below the 800 °C heat treatment, returning the sample roughness and even increasing it, after higher temperature treatments [21,22].…”

“…EDS analysis determined a bioglass 45S5 characteristic spectrum [21] in both systems: the native bioglass (BGs1:3) and the silver-doped bioglass (BGsAg1:3). The presence of contamination by precursors (Fig.…”

In vitro endothelial cell response to ionic dissolution products from boron-doped bioactive glass in the SiO2–CaO–P2O5–Na2O system

“…47 In accordance with these studies, Handel et al showed that minimal medium containing 1% of crushed 45S5 Bioglass®-based scaffolds induced a signicant proliferation of HUVECs. 48 However, these results do not agree with those by Aina et al, who showed that proliferation of endothelial cells from bovine aorta (BAE-1) in 45S5 Bioglass® used as the substrate was lower than that observed using 45S5 BG modied with 5% ZnO (wt%). 49 The authors attributed the lower proliferation rate to the alkaline pH resulting from the sudden release of ions from 45S5 BG.…”

Dynamic Fabrication of Tissue-Engineered Bone Substitutes Based on Derived Cancellous Bone Scaffold in a Spinner Flask Bioreactor System

“…In respect to the cells, the bone-derived seed cells can easily differentiate into osteoblasts in vitro; the bone, embryonic bone, and new bone are therefore the optimal sources of seed cells for bone tissue engineering [33,34]. However, it is very difficult to harvest, and the in vitro cell number is thus limited each time.…”