Evaluation of borate bioactive glass scaffolds as a controlled delivery system for copper ions in stimulating osteogenesis and angiogenesis in bone healing

Abstract

Biocompatible synthetic scaffolds with enhanced osteogenic and angiogenic capacity are of great interest for the repair of large (critical size) bone defects. In this study, we investigated an approach based on the controlled delivery of copper (Cu) ions from borate bioactive glass scaffolds for stimulating angiogenesis and osteogenesis in a rodent calvarial defect model. Borate glass scaffolds (pore size ¼ 200-400 mm) doped with varying amounts of Cu (0-3.0 wt% CuO) were created using a polymer foam replication technique. When immersed in simulated body fluid (SBF) in vitro, the scaffolds released Cu ions into the medium at a rate that was dependent on the amount of Cu in the glass and simultaneously converted to hydroxyapatite (HA). At the concentrations used, the Cu in the glass was not cytotoxic to human bone marrow derived stem cells (hBMSCs) cultured on the scaffolds and the alkaline phosphatase activity of the hBMSCs increased with increasing Cu in the glass. When implanted in rat calvarial defects for 8 weeks, the scaffolds doped with 3 wt% CuO showed a significantly better capacity to stimulate angiogenesis and regenerate bone when compared to the undoped glass scaffolds. Together, these results indicate that the controlled delivery of Cu ions from borate bioactive glass implants is a promising approach in healing bone defects.

Effect of ion release from Cu-doped 45S5 Bioglass® on 3D endothelial cell morphogenesis

“…The incorporation of copper into mesoporous high-silicate glass scaffolds as well as a calcium silicate bioceramic was shown to enhance (HIF)-1a and VEGF expression and, as a result, EC morphogenesis [32,33]. Moreover, copper-doped borosilicate glasses stimulated in vivo angiogenesis and bone regeneration [34,35]. Recently, copper-doped 45S5 Bioglass Ò -derived scaffolds were developed and characterized in terms of their dissolution reactions [36].…”

Timing of calcium nitrate addition affects morphology, dispersity and composition of bioactive glass nanoparticles

“…1,2 In addition, BG can be fabricated conveniently in diverse morphologies, including three-dimensional scaffolds, 3 bers, 4 coatings, 5 and nanoparticles, 6 for specic biomedical applications. Spherical bioactive glass nanoparticles (BGN) have started to attract increasing attention, 7 due to their small size and large specic surface area which consequently lead to their high bioactivity and enhanced protein adsorption.…”

Destructive and Non-Destructive Properties of Cobalt Oxide Substituted 1393 Bioactive Glass

“…These new glasses are highly beneficial as they help in the process of osteogenesis and angiogenesis and act as an anti-bacterial agent in chemical applications of engineered bone constructs. [18][19][20][21][22] They are of importance as they can be used for the limited delivery of certain ions which control particular cell functions 23 , the carrier of homeostatic agents 24 and therapeutic drugs 25 , hyperthermia treatment of cancer 26 and also for soft tissue applications like nerve generation. 27 1393 bioactive glasses tolerate strong bonding to hard and soft tissue and have been shown to endorse osteogenesis via the activation of several relevant genes.…”