Hypoxia-Mimicking Cobalt-Doped Borosilicate Bioactive Glass Scaffolds with Enhanced Angiogenic and Osteogenic Capacity for Bone Regeneration

Abstract

The osteogenic capacity of synthetic bone substitutes is will be highly stimulated by a well-established functional vascularized network. Cobalt (Co) ions are known that can generate a hypoxia-like response and stimulates the production of kinds of angiogenic factors. Herein, we investigated the mechanism of cobalt-doped bioactive borosilicate (36B 2 O 3 , 22CaO, 18SiO 2 , 8MgO, 8K 2 O, 6Na 2 O, 2P 2 O 5 ; mol%) glass scaffolds for bone tissues repairing and blood vessel formation in the critical-sized cranial defect site of rats and their effects on the hBMSCs in vitro were researched. The scaffolds can control release Co 2+ ions and convert into hydroxyapatite soaking in simulative body fluids (SBF). The fabircated scaffolds without cytotoxic strongly improves HIF-1α generation, VEGF protein secretion, ALP activity and upregulates the expression of osteoblast and angiogenic relative genes in hBMSCs. Eight weeks after implantation, the bioactive glass scaffolds with 3wt % CoO remarkablely enhance bone regeneration and blood vascularized network at the defective site. In conclusion, as a graft material for bone defects, low-oxygen simulated cobalt-doped bioactive glass scaffold is promising.

Strontium- and Cobalt-Doped Multicomponent Mesoporous Bioactive Glasses (MBGs) for Potential Use in Bone Tissue Engineering Applications

“…The mobility of the HUVECs treated with the MBGs showed an increase at 24 h post-incubation ( Figure 12). These results are in good agreement with prior reports [20,52,53], and provide early evidence of the ability of Sr/Co-doped MBGs to potentially induce angiogenesis.…”

Angiogenesis in Tissue Engineering: As Nature Intended?

“…Low oxygen concentration is a potent regulator of angiogenesis, driving sprouting of ECs toward the deficient tissue (Pugh and Ratcliffe, 2003;Ziyad and Iruela-Arispe, 2011;Viallard and Larrivée, 2017;Petrova et al, 2018) through hypoxia inducible factor-dependent increase of VEGF transcription (Liao and Johnson, 2007;Oladipupo et al, 2011). Recreating a hypoxic environment has been revealed to be useful for therapeutic angiogenesis in bone TE both in vitro and in vivo (Wu et al, 2012;Deng et al, 2019). Wu et al (2012) developed a porous cobalt-containing mesopore-bioglass scaffold able to release ionic Co 2+ , inducing a hypoxic-mediated response in human bone marrow stromal cells.…”

“…Wu et al (2012) developed a porous cobalt-containing mesopore-bioglass scaffold able to release ionic Co 2+ , inducing a hypoxic-mediated response in human bone marrow stromal cells. Similarly, Deng et al (2019) used a cobalt-doped bioactive borosilicate glass scaffold in vivo, showing improved vascularization and regeneration of bone tissue after implantation in rats with a calvarial defect.…”

Intraperitoneal injection of Desferal® alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats

“…Previously, we also found that activating the HIF pathway in bone progenitor cells by deletion of the von Hippel Lindau gene antagonizes age-related bone loss [ 15 ]. In addition, some studies suggested that pretreating with hypoxia or hypoxia mimics improved the osteogenic and angiogenic ability of BMSCs and enhanced bone repair in bone tissue engineering [ 16 , 17 ]. Based on those findings, we propose the hypothesis that pharmacological manipulation of a hypoxic niche would attenuate age-related bone loss and rejuvenate the senescence of BMSCs.…”