Novel injectable gellan gum hydrogel composites incorporating Zn- and Sr-enriched bioactive glass microparticles: High-resolution X-ray microcomputed tomography, antibacterial and in vitro testing

Abstract

Mineralization of hydrogel biomaterials is desirable to improve their suitability as materials for bone regeneration. In this study, gellan gum (GG) hydrogels were formed by simple mixing of GG solution with bioactive glass microparticles of 45S5 composition, leading to hydrogel formation by ion release from the amorphous bioactive glass microparticles. This resulted in novel injectable, self-gelling composites of GG hydrogels containing 20% bioactive glass. Gelation occurred within 20 min. Composites containing the standard 45S5 bioactive glass preparation were markedly less stiff. X-ray microcomputed tomography proved to be a highly sensitive technique capable of detecting microparticles of diameter approximately 8 μm, that is, individual microparticles, and accurately visualizing the size distribution of bioactive glass microparticles and their aggregates, and their distribution in GG hydrogels. The widely used melt-derived 45S5 preparation served as a standard and was compared with a calcium-rich, sol-gel derived preparation (A2), as well as A2 enriched with zinc (A2Zn5) and strontium (A2Sr5). A2, A2Zn, and A2Sr bioactive glass particles were more homogeneously dispersed in GG hydrogels than 45S5. Composites containing all four bioactive glass preparations exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus. Composites containing A2Zn5 and A2Sr5 bioactive glasses supported the adhesion and growth of osteoblast-like cells and were considerably more cytocompatible than 45S5. All composites underwent mineralization with calcium-deficient hydroxyapatite upon incubation in simulated body fluid. The extent of mineralization appeared to be greatest for composites containing A2Zn5 and 45S5. The results underline the importance of the choice of bioactive glass when preparing injectable, self-gelling composites.

Pectin-bioactive glass self-gelling, injectable composites with high antibacterial activity

“…A well-spread morphology and high viability of the osteoblastic cells seeded in vicinity of composite hydrogels, as well as large numbers of the cells in 5× and 10× diluted eluates ( Figure 3C) would appear to support these hypotheses. The results of in vitro cell tests observed in this study are consistent with findings reported in our previous works concerning gellan gum (GG) modified with BG particles of the same chemical composition as used here (Douglas et al, 2014;Douglas, Dziadek, et al, 2018). The reasons for the greater number of cells cultured in undiluted eluate from CA-2.5 composite hydrogels remain unclear.…”

“…The result (Figure 2) reinforces the observation made in previous work that µCT technique are useful tools to study inorganic particle distribution in hydrogel matrices (Douglas et al, 2014(Douglas et al, , 2016Douglas, Dziadek, et al, 2018;Douglas, Schietse, et al, 2018;Gorodzha et al, 2016). Hence, one can expect that µCT can be exploited to develop strategies to reduce microparticle aggregation and improve their dispersion.…”

“…Thus, the strong antibacterial activity of pectin-BG composite hydrogels against MRSA strain Mu50 can be correlated with an increase in Ca 2+ concentration and alkalization of the bacterial culture medium, confirmed in mineralization studies ( Figure 6A). Also in our previous research, strong and extremely fast alkalization of ddH 2 O (pH = 11.6) and PBS (pH = 9.5) during zeta potential measurements of BG (at a concentration 1 mg/ml) was reported (Douglas, Dziadek, et al, 2018;Gorodzha et al, 2016). Antibacterial properties of composites observed in this work ( Figure 3D) are significantly enhanced in comparison with GG hydrogels containing bioactive glass particles of the same chemical composition as used in present work (Douglas et al, 2014;Douglas, Dziadek, et al, 2018).…”

<p>Gadolinium-doped bioglass scaffolds promote osteogenic differentiation of hBMSC via the Akt/GSK3&beta; pathway and facilitate bone repair in vivo</p>

“…[2][3][4][5][6] Numerous studies have revealed that hierarchically porous characteristics and bioactive components could effectively regulate cellular performances such as attachment, migration, proliferation, and differentiation. [10][11][12][13][14][15] In particular, Gd element is found in human bones and plays a key role in bone tissue growth and regeneration. [19][20][21][22] In this study, we successfully fabricated Gd-BG scaffolds with hierarchical pores and bioactive Gd element for effective bone defect healing.…”

“…14 Recently, the incorporation of trace bioactive elements such as Ag, Cu, Sr, and Zn in BG was found to enhance the antibacterial property, osteogenic activity, and angiogenic capacity. 10,15 Incorporation of lanthanide elements into BG have been widely investigated. Lanthanides have been shown to functionally mimic calcium and treat bone density disorders.…”