## 6 Borate-Based BGs in Peripheral Nerve Regeneration  
The effectiveness of borate BGs for tissue-engineering-based therapies is completely accepted due to the capability of boron ions to improve cell proliferation, promote angiogenesis, and reduce inflammation [80; 81; 82]. The therapeutic effects of boric acid on peripheral nerve regeneration were previously studied [83]; the administration of 100 mg/kg of boric acid (four times per day) can reduce axonal and myelin damages in the sciatic nerve injury model in rats. Moreover, it has been reported that piezoelectric stimulation mediated by boron nitride nanotubes can be applied to improve the neurite length of PC12 cells in vitro [84]. Recent studies showed that boron can be easily loaded into chitosan/collagen hydrogels and promotes key biological functions such as angiogenesis [85]. Borate BGs have recently attracted much attention in the context of soft tissue healing applications [86]. In vitro experimental data confirmed that borate-based glasses have the ability to induce stem cells to secrete a series of proteins, including collagen, angiogenic, and VEGF [87]. There is a paucity of studies focused on nerve regeneration, but the early available results are promising (see Table 1) and justify further investigations. The cytocompatibility of 13-93B3 glass rods and microfibers (formulation: 53B\({}_{2}\)O\({}_{3}\)-20 CaO-6 Na\({}_{2}\)O-12K\({}_{2}\)O-5 MgO-4P\({}_{2}\)O wt.%) with neuronal cells was documented by [PERSON] et al. in 2013 [23]. Similar to silicate- and phosphate-based glasses, the borate glass scaffolds could increase the percentage of living neurons in vitro. Moreover, the aligned glass rods supported oriented neurite growth (see Figure 7). Figure 6: (**A**) Schematic illustration of animated phosphate glass fibers (PGFs) interfaced with carbon nanotubes (CNTs) through carboxyl groups to wrap around a poly(L/D-lactic acid) (PLDLA) electrospun nanofiber mat and fabricate a porous PLDLA cylindrical tube. (**B**) In vivo implantation of the composite scaffolds into the proximal and distal stumps of a completely transected sciatic nerve of rats (a) and histological and immunohistochemical images at 16 weeks post-implantation (b,c) clarifying the regenerative effect of the scaffolds. Yellow scale bar = 500 μm, black scale bar = 50 μm. Reproduced with some modifications from ref [79]. Several experiments have documented that borate BGs show better mechanical, physicochemical, and biological properties after the incorporation of metallic cations (e.g., Ti\({}^{4+}\), Cu\({}^{2+}\), Zn\({}^{2+}\), etc.) into their network [88, 89]. These dopants typically increase borate glass durability upon contact with aqueous fluids. Ion-doped borate BGs have also been developed for potential use in peripheral nerve  
Figure 7: (**A**) SEM micrographs of melt-derived 13-93 B3 borate BGs in rod (a,c) and microfiber (b,d) forms. (**B**) Microscopic images of embryonic chick dorsal root ganglia (DRG) cells alone (control groups al/a2 and d1/d2) or treated with 13-93 B3 rods (b1/b2 and e1/e2) and microfibers (c1/c2 and f1/2). Note that the images were captured from the cells after 6 days of culture. The culture medium was exchanged every other day (transient condition) in the two top rows, while no medium was exchanged throughout the experiment (static condition) in the two bottom rows. Scale bar is 100 μm. Reproduced with some modifications from ref [23]. regeneration. [PERSON] et al. synthesized a series of borate-based BGs containing various therapeutic elements, including Ag, Ce, Cu, Fe, Ga, I, Y, and Zn [58]. The results showed that Fe-, Ga-, and Zn-doped BGs could successfully promote the survival and outgrowth of neurons, whereas I-doped BGs were the most detrimental to neurons. Prior studies have shown that borate-based BGs can be mixed with polymers to fabricate electrospun composites as 3D biomimetic structures [90].