Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications

Abstract

Introduction and Methods: Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway. Here, novel glass fibres were produced by laser spinning. The hypothesis was that silicate glass fibres that deliver cobalt ions will activate the HIF pathway and promote the expression of angiogenic genes. The glass composition was designed to biodegrade and release ions, but not form a hydroxyapatite layer in body fluid.Results and Discussion: Dissolution studies demonstrated that hydroxyapatite did not form. When keratinocyte cells were exposed to conditioned media from the cobalt-containing glass fibres, significantly higher amounts of HIF-1α and Vascular Endothelial Growth Factor (VEGF) were measured compared to when the cells were exposed to media with equivalent amounts of cobalt chloride. This was attributed to a synergistic effect of the combination of cobalt and other therapeutic ions released from the glass. The effect was also much greater than the sum of HIF-1α and VEGF expression when the cells were cultured with cobalt ions and with dissolution products from the Co-free glass, and was proven to not be due to a rise in pH. The ability of the glass fibres to activate the HIF-1 pathway and promote VEGF expression shows the potential for their use in chronic wound dressings.

Double hits with bioactive nanozyme based on cobalt-doped nanoglass for acute and diabetic wound therapies through anti-inflammatory and pro-angiogenic functions

“…Of note, this was reasoned to be due to the presence of “Co 3 O 4 ” tiny crystallites distributed in the CoNZ nanoparticles, which is believed to form in situ through the chemical reaction with H 2 O 2 , ultimately playing a key role in scavenging various ROS. This distinctive property exhibited by Co 3 O 4 crystallites represents a novel finding with potential implications for mitigating inflammatory-driven diabetic conditions, while the effects of Co-doped bioactive glass on wound healing have been previously documented in other studies [ [32] , [33] , [34] , [35] ].

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“…With these in mind, here we propose a biomaterial-based drug-free therapeutic approach for pathological wound, particularly diabetic skin wound. We present a novel bioactive nanozyme based on cobalt-doped nanoglass (namely, CoNZ), which possesses high enzymatic and catalytic (‘anti-inflammatory’) capability while releasing therapeutic (‘pro-angiogenic’) ions [ [32] , [33] , [34] , [35] ]. Among other ions that can be doped to nanoglass, cobalt is particularly noteworthy because we discovered the in situ production of cobalt oxide “Co 3 O 4 ” tiny crystallites through chemical reactions with ROS (mainly H 2 O 2 ) within the CoNZ network, which proven to play a decisive role in scavenging various ROS and inhibiting inflammatory cascade.…”

Cobalt-Doped Bioactive Glasses for Biomedical Applications: A Review

“…Melt-derived multicomponent Co-containing glass particles were also mixed with polycaprolactone (PCL) to produce extrudable inks for use in the manufacturing of 3Dprinted scaffolds [50], with electrospun fish-derived collagen fibers to fabricate fibrous composite mats [51], or with bovine collagen/glycosaminoglycans to obtain ultra-porous composite scaffolds [52]. Successful production of single-phase fibrous glass scaffolds was also reported by direct laser spinning of glass fibers (Figure 3) [53].…”

Insulin–cobalt core–shell nanoparticles for receptor-targeted bioimaging and diabetic wound healing

“…50 The synthesis of silicate glass bers for delivering the cobalt ions was done for their chronic wound healing activity by activating the HIF pathway and enhancing the expression of angiogenic genes. 51 Similarly, a bioactive glass was made using the sol-gel method and doped with two different metal ions, including silver and cobalt, for their antibacterial activity in the case of wound healing applications. 52 In this work, we are reporting the synthesis of novel proteincoated metal core-shell nanoparticles for their in vitro normal and diabetic wound healing and bioimaging application for the rst time.…”

“… 50 The synthesis of silicate glass fibers for delivering the cobalt ions was done for their chronic wound healing activity by activating the HIF pathway and enhancing the expression of angiogenic genes. 51 Similarly, a bioactive glass was made using the sol–gel method and doped with two different metal ions, including silver and cobalt, for their antibacterial activity in the case of wound healing applications. 52 …”