Evaluation of in vivo angiogenetic effects of copper doped bioactive glass scaffolds in the AV loop model

Abstract

Abstracteffects of 3D scaffolds made from 45S5 bioactive glass (BG) doped with 1 wt. % copper ions in the arteriovenous loop model of the rat.Materials and Methods: An arteriovenous loop was built in the groin of 10 rats and inserted in 1% copper doped 45S5 BG scaffolds and fibrin. The scaffold and the AV loop were inserted in Teflon isolation chambers and explanted 3 weeks after implantation. Afterwards the scaffolds were analyzed by Micro-CT and histology regarding vascularization. Results were compared to plain 45S5 BG-based scaffolds from a previous study.Results: Micro-CT and histological evaluation showed consistent vascularization of the constructs. A tendency towards an increased vascularization in the copper doped BG group compared to plain BG constructs could be observed. However, therewas no significant difference in statistical analysis between both groups.Conclusions: This study shows results that support an increased angiogenetic effect of 1% copper doped 45S5 BG compared to regular 45S5 BG scaffolds in the rat arteriovenous loop model although these tendencies are not backed by statistical evidence. Maybe higher copper doses could lead to a statistically significant angiogenetic effect.

3D Scaffolds of Polycaprolactone/Copper-Doped Bioactive Glass: Architecture Engineering with Additive Manufacturing and Cellular Assessments in a Coculture of Bone Marrow Stem Cells and Endothelial Cells

“…However, we may speculate whether the S53P4 BaG itself promotes angiogenesis, and the addition of Cu 2+ that was released from the scaffold of PCL:S53P4–Cu1 = 4:1 does not suffice to produce observable differences in tubular network formation. A similar finding was also reported in an in vivo evaluation of the angiogenetic effect of the Cu-doped 45S5 scaffolds in the AV loop model: a tendency toward an increased vascularization in the Cu-doped BaG group compared to the plain BaG group was observed in μ-CT and histological evaluations, but no statistical difference in vascularization could be measured between both groups . Altogether, the PCL:S53P4 = 4:1 and PCL:S53P4–Cu1 = 4:1 scaffolds supported the vascularization and tubular formation in the coculture setup; however, the angiogenic effect of Cu 2+ was not notable in contrast to the PCL/BaG composite.…”

In VivoAnalysis of the Immune Response to Strontium- and Copper-doped Bioglass

“…Altogether, neither of these therapeutic ions had any biological influence on the immune response or the vascularization pattern. This result is surprising as both ions have been described to influence both molecular cascades but are in line with another in vivo study including an analysis of silicate-based copper-doping that also showed no influence and, more importantly, the materials in fact hindered the regeneration process (62,64).…”

Bioactive Glasses: Where Are We and Where Are We Going?

“…The release of Ca 2+ ions is also suspected to play an important role in the late stages of healing, and the presence of calcium in the immediate vicinity of an open wound seems to help the body to regulate wound healing processes more effectively, particularly in open wounds. Doping with small amounts of selected ions, e.g., Cu 2+ [ 89 ], can further potentiate the angiogenetic effect of BGs. Copper is known to regulate a number of factors involved in angiogenesis, such as vascular endothelial growth factor (VEGF), fibronectin, angiogenin, and fibroblast growth factor (FGF) 1 and 2, which play key roles in the initiation (vasodilation and vascular permeabilization), maturation (endothelial cell proliferation, migration and morphogenesis), and regulation of blood vessel formation (ECM remodeling) [ 90 ].…”