2.2.2. Nano Bioglass

Bioglasses (BG) have been intensively investigated as biomaterials since their discovery in 1969 and first developments in the 1970s made by L. Hench [260]. Compared to common glass, bioglass contains less silica and higher amounts of calcium and phosphorous. As a biomaterial for tissue engineering, bioglass is applied independently or in combination with a number of polymers [261] (Figure 13). BG can arouse fibroblasts with higher bioactivity by accelerating bioactive growth factors and proteins as compared to untreated fibroblasts [262].

**Figure 13.** Biomedical applications of hydroxyapatite and glass ceramics.

BG degrade slowly when implanted into the targeted patient's site and release ions, which favors the biosynthesis of hydroxyapatite [263]. The silica-rich surface of bioglass promotes the exchange of Ca2<sup>+</sup> and PO4 <sup>3</sup><sup>−</sup> with physiological fluid, which leads to the generation of a Ca–P layer [264,265]. This biodegradation may be enhanced by the presence of a SiO2 network, which forms non-bridging silicon-oxygen bonds [266]; the low connectivity of the SiO2 network enhances dissolution of bioglass while the presence of Na and Ca forms Si–O–Si bonds and reduces dissolution rate. Mesoporous BG can be fabricated using the sol-gel method, which can be a good carrier for targeted drug delivery [267]. The sol–gel method was also used by Kumar et al. [268] to develop bioglass nanoparticles with a higher content of silica, which are suited for bone tissue applications.

Bioglass nanoparticles show high biocompatibility and surface area, which can enhance in vitro osteoconductivity as compared to layer and microsized particles of bioglass [269]. The size of the particles can be modified by changing the synthesis parameters and techniques. However, because of its brittleness, the glass alone cannot be used to heal large bone defects [270]. In order to solve this issue, Bioglass 45S5 was used with poly(D,L-lactide) (PDLLA), a biodegradable polymer, to form a composite scaffold with enhanced biomechanical characteristics [271]. The early failure of a bioglass composite at the interface occurs because of nonuniform mechanical strength, phase separation, nonhomogeneous mixture, and different degradation properties of two compounds. A hybrid composite of poly(methyl methacrylate) (PMMA) and bioactive glass was manufactured via the sol-gel method (Figure 14) to enhance physicochemical and mechanical properties [272].

An elastin-like polypeptidic and bioglass (ELP/BG) hydrogel was also fabricated that is mechanically robust, injectable, and self-healable. This ELP/BG biocomposite can be useful for drug delivery and tissue engineering purposes [273]. A 3D construct of type-I collagen and 45S5 Bioglass meets the basic requirements of a scaffold including biocompatibility, osteoconductivity, osteoinductivity, and biodegradability [274]. Bioglass nanoparticles were also used with bacterially derived poly(3-hydroxybutyrate) to fabricate bioactive composite film using a fermentation technique [275]. Different glass modifiers (Mg2+, Ca2+, and Sr2+) were used to prepare borosilicate bioactive glasses through a melt-quenching technique which showed good antibacterial properties [276]. Poly(propylene fumarate) (PPF) was used to functionalize bioglass particles that enhance the bioactivity and cell adhesion, proliferation, and bone regeneration [277].

**Figure 14.** Schematic procedure for the fabrication of a PMMA-bioglass class II hybrid (Adapted with permission from © 2013 American Chemical Society [272]).
