## 5 Phosphate-Based BGs in Peripheral Nerve Regeneration  
Although most studies involving phosphate-based BGs have addressed hard tissue engineering [71; 72; 73; 74; 75], there is recent evidence supporting the suitability of this kind of glass in peripheral nerve regeneration, too (Table 1). In fact, phosphate glass fibers were shown to play an effective role in promoting neurite outgrowth in vitro and peripheral nerve regeneration in vivo [24]. [PERSON] et al. synthesized 50P\({}_{2}\)O\({}_{5}\)-40 CaO-5 Na\({}_{2}\)O-5 Fe\({}_{2}\)O\({}_{3}\) (mol.%) phosphate BG fibers (\(14.99\pm 2.77\)\(\upmu\)m in diameter) by using a melt-spinning method and successfully aligned the fibers on a compressed collagen matrix while rolling them into a nerve conduit. These composite tubular scaffolds showed positive effects on the outgrowth of adult dorsal root ganglion (DRG) neurons in vitro. Moreover, the authors observed the ability of the scaffolds to allow axon extension and the recovery of plantar muscle atrophy at 1 and 8 weeks post-implantation in transected sciatic nerves of rats. However, no significant differences were recorded between the BG-containing scaffolds and their glass-free counterparts regarding the number of axons, muscle atrophy, or motor and sensory functions 12 weeks after implantation (see Figure 3). Full regeneration of a spinal cord injury is one of the ultimate targets in neuroregenerative medicine strategies. To this end, 3D composite hydrogel scaffolds made of phosphate BG and collagen were evaluated in a rodent model of transected rat spinal cord [76]. The glass formulation was 50P\({}_{2}\)O\({}_{5}\)-40 CaO-5 Na\({}_{2}\)O-5 Fe\({}_{2}\)O\({}_{3}\) (mol.%), and aligned fibers with a diameter of 18.49 \(\pm\) 4.74 \(\upmu\)m were produced to examine the healing properties. High levels of calcium and iron in the glass resulted in less soluble fibers to better support neuronal growth. The prepared constructs were implanted  
Figure 3: (**A**) Composite scaffolds of phosphate glass fibers (PGfs) and collagen (Col) designed for peripheral nerve regeneration: (a) and (b) demonstrate the manufacturing process of the scaffolds and their scanning microscopy (SEM) photographs (scale bar = 100 \(\upmu\)m). (c), (d), and (e) show the surgery procedure related to complete transection of the sciatic nerve, the implantation of the composites (0.8 mm diameter, 3 mm long), and suturing of the neural sheath with 10-0 nylon suture, respectively. (**B**) Illustration of immunohistochemical staining of animal axons within the (a) cross-section of an intact sciatic nerve; (b) cross-section of the scaffold collagen group; and (c) PGf/collagen scaffolds at 7 days post-surgery. (d) and (e) exhibit magnified images of the yellow boxes in (c). (f) and (g) represent high-magnification images of the white boxes in (c) (white scale bar = 200 \(\upmu\)m, yellow scale bar = 20 \(\upmu\)m). Cross-sectional images 1 mm distal from (h) the collagen group and (i) the PGf/collagen group at 8 weeks post-implantation, and (j) the collagen group and (k) the PGf/collagen group after 12 weeks. (l) shows the number of axons at 1 mm distal to the scaffolds 8 and 12 weeks post-implantation. DIC: differential interference contrast microscope. DAPI: 4’,6-diamidino-2-phenylindole. Reproduced with permission from ref [24]. into completely transected rat spinal cords, and the outcomes were compared with those of glass-free collagen scaffolds. The obtained results revealed axon growth from the proximal and distal stumps to the glass-containing scaffolds after 12 postoperative weeks due to the directional guidance for outgrowing axons (Figure 4). Additionally, an improvement in locomotion ability was observed in the experimental groups receiving the glass-containing implant as compared to the controls after 12 weeks of implantation. At the same time, the mRNA levels of brain-derived neurotrophic factor (BDNF) in the bladder of rats were increased more in the glass-containing hydrogel scaffolds than in the control.