In vitro and in ovo impact of the ionic dissolution products of boron-doped bioactive silicate glasses on cell viability, osteogenesis and angiogenesis

Abstract

Due to the pivotal role of angiogenesis in bone regeneration, the angiogenic properties of biomaterials are of high importance since they directly correlate with the biomaterials’ osteogenic potential via ‘angiogenic-osteogenic coupling’ mechanisms. The impact of bioactive glasses (BGs) on vascularization can be tailored by incorporation of biologically active ions such as boron (B). Based on the ICIE16-BG composition (in mol%: 49.5 SiO2, 36.3 CaO, 6.6 Na2O, 1.1 P2O5, 6.6 K2O), three B-doped BGs have been developed (compositions in mol%: 46.5/45.5/41.5 SiO2, 36.3 CaO, 6.6 Na2O, 1.1 P2O5, 6.6 K2O, 3/4/8 B2O3). The influence of B-doping on the viability, cellular osteogenic differentiation and expression of osteogenic and angiogenic marker genes of bone marrow-derived mesenchymal stromal cells (BMSCs) was analyzed by cultivating BMSCs in presence of the BGs’ ionic dissolution products (IDPs). Furthermore, the influence of the IDPs on angiogenesis was evaluated in ovo using a chorioallantoic membrane (CAM) assay. The influence of B-doped BGs on BMSC viability was dose-dependent, with higher B concentrations showing limited negative effects. B-doping led to a slight stimulation of osteogenesis and angiogenesis in vitro. In contrast to that, B-doping significantly enhanced vascularization in ovo, especially in higher concentrations. Differences between the results of the in vitro and in ovo part of this study might be explained via the different importance of vascularization in both settings. The implementation of new experimental models that cover the ‘angiogenic-osteogenic coupling’ mechanisms is highly relevant, for instance via extending the application of the CAM assay from solely angiogenic to angiogenic and osteogenic purposes.

Investigation of in vitro bioactivity, and osteoblast and angiogenic activity of spray-dried boron-doped 58S bioactive glass microspheres

“…Further, the addition of B showed significant increases in cell viability, suggesting that the addition of B is capable of stimulating the secretion of angiogenic growth factors. 16,17 In summary, the results indicated that incorporating B in 58S BG specimens could facilitate osteoblast and angiogenic activity, showing a good agreement with previous works. 35…”

“…Boron, in particular, has been widely shown to induce angiogenesis in both in vitro and in vivo investigations, which could be greatly utilized for so tissue repair applications that require vascularization. 17 In addition, the incorporation of B ions into different proportions of BGs has shown signicant effects on bioactivity and osteoblast activity. 18 To date, the sol-gel method stands as one of the prevailing techniques used for the preparation of B-doped BG.…”

The effect of Wharton’s jelly-derived stem cells seeded/boron-loaded acellular scaffolds on the healing of full-thickness burn wounds in the rat model

“…Therefore, the current study was planned and conducted to introduce a new acellular dermal scaffold equipped with a combination of hWJMSCs/B and assess this natural modified tissue influences on angiogenesis and regeneration of dermal defects in third-degree skin burns rats [40]. Our findings represented compelling data that B/hWJMSCs-AOSIS significantly accelerated the healing of burn wounds by decreasing inflammatory response, promoting angiogenesis, enhancing re-epithelialization and preventing exaggerated scar tissue formation in the wound area [18,41].…”

Chitosan-Boric Acid Scaffolds for Doxorubicin Delivery in the Osteosarcoma Treatment

“…The rapid release of B from the scaffolds might also be facilitated by the high swelling capacity characteristic of chitosan-based scaffolds. As a therapeutic agent, boron is usually incorporated into bioactive glasses to modulate angiogenesis and neovascularization and to have a slower controlled release from the materials in the physiological microenvironment [ 48 ]. Recent studies on synthetic and natural polymers modified by borax and boric acid as boron precursors indicated enhanced vascularization and angiogenesis provided by rapid or moderate boron delivery at lower concentrations [ 26 , 40 ].…”