Abstract
Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The “classical” elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even “exotic” for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.
Highlights
Bioactive glasses (BGs) are being increasingly investigated for both bone and soft tissue engineering applications [1, 2]
A significant number of BGs doped with what can be called less-common ions, including rare earth elements, have started to be reported. Such BGs are attractive for tissue regeneration applications because of the functional properties, biological activity, and therapeutic effects provided by such ions
He et al [141] reported that BGNs with Rb content greater than 3 mol% were toxic to human umbilical vein endothelial cells (HUVECs), fibroblasts, and HaCaTs cells, while BGNs with Rb contents less than or equal to 3 mol% were nontoxic to the same cells
Summary
Bioactive glasses (BGs) are being increasingly investigated for both bone and soft tissue engineering applications [1, 2]. The use of several biologically active ions has been prevalent in recent years, namely, Ag+, Li+, Co2+, Ca2+, Cu2+, Zn2+, Sr2+, Fe2+, Mg2+, Ga3+, and B3+ have been added to silicate, phosphate, and borate BG systems to promote functional properties such as osteogenesis, angiogenesis, bioactivity, antibacterial effects, and immunomodulation for tissue regeneration, as well as for infection and cancer treatment [40, 47, 48]. A significant number of BGs doped with what can be called less-common (or even exotic) ions, including rare earth elements, have started to be reported. Such BGs are attractive for tissue regeneration applications because of the functional properties, biological activity, and therapeutic effects provided by such ions. Ions used in less than 30 publications (up to August 31, 2021) were considered “less-common ions” and were included in this review (clearly this is an arbitrarily chosen number, but necessary to establish a criterion to identify such less-common ions)
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