Tissue Bioengineering with Fibrin Scaffolds and Deproteinized Bone Matrix Associated or Not with the Transoperative Laser Photobiomodulation Protocol.

Extending the range of use of the heterologous fibrin biopolymer, this pre-clinical study showed a new proportionality of its components directed to the formation of scaffold with a lower density of the resulting mesh to facilitate the infiltration of bone cells, and combined with therapy by laser photobiomodulation, in order to accelerate the repair process and decrease the morphofunctional recovery time. Thus, a transoperative protocol of laser photobiomodulation (L) was evaluated in critical bone defects filled with deproteinized bovine bone particles (P) associated with heterologous fibrin biopolymer (HF). The groups were: BCL (blood clot + laser); HF; HFL; PHF (P+HF); PHFL (P+HF+L). Microtomographically, bone volume (BV) at 14 days, was higher in the PHF and PHFL groups (10.45 ± 3.31 mm3 and 9.94 ± 1.51 mm3), significantly increasing in the BCL, HFL and PHFL groups. Histologically, in all experimental groups, the defects were not reestablished either in the external cortical bone or in the epidural, occurring only in partial bone repair. At 42 days, the bone area (BA) increased in all groups, being significantly higher in the laser-treated groups. The quantification of bone collagen fibers showed that the percentage of collagen fibers in the bone tissue was similar between the groups for each experimental period, but significantly higher at 42 days (35.71 ± 6.89%) compared to 14 days (18.94 ± 6.86%). It can be concluded that the results of the present study denote potential effects of laser radiation capable of inducing functional bone regeneration, through the synergistic combination of biomaterials and the new ratio of heterologous fibrin biopolymer components (1:1:1) was able to make the resulting fibrin mesh less dense and susceptible to cellular permeability. Thus, the best fibrinogen concentration should be evaluated to find the ideal heterologous fibrin scaffold.

Influence of the Neuroprotective Properties of Quercetin on Regeneration and Functional Recovery of the Nervous System.

Quercetin is a dietary flavonoid present in vegetables, fruits, and beverages, such as onions, apples, broccoli, berries, citrus fruits, tea, and red wine. Flavonoids have antioxidant and anti-inflammatory effects, acting in the prevention of several diseases. Quercetin also has neuroprotective properties and may exert a beneficial effect on nervous tissue. In this literature review, we compiled in vivo studies that investigated the effect of quercetin on regeneration and functional recovery of the central and peripheral nervous system. In spinal cord injuries (SCI), quercetin administration favored axonal regeneration and recovery of locomotor capacity, significantly improving electrophysiological parameters. Quercetin reduced edema, neutrophil infiltration, cystic cavity formation, reactive oxygen species production, and pro-inflammatory cytokine synthesis, while favoring an increase in levels of anti-inflammatory cytokines, minimizing tissue damage in SCI models. In addition, the association of quercetin with mesenchymal stromal cells transplantation had a synergistic neuroprotective effect on spinal cord injury. Similarly, in sciatic nerve injuries, quercetin favored and accelerated sensory and motor recovery, reducing muscle atrophy. In these models, quercetin significantly inhibited oxidative stress and cell apoptosis, favoring Schwann cell proliferation and nerve fiber remyelination, thus promoting a significant increase in the number and diameter of myelinated fibers. Although there is still a lack of clinical research, in vivo studies have shown that quercetin contributed to the recovery of neurological functions, exerting a beneficial effect on the regeneration of the central and peripheral nervous system.

Use of Photobiomodulation Combined with Fibrin Sealant and Bone Substitute Improving the Bone Repair of Critical Defects.

In this preclinical protocol, an adjunct method is used in an attempt to overcome the limitations of conventional therapeutic approaches applied to bone repair of large bone defects filled with scaffolds. Thus, we evaluate the effects of photobiomodulation therapy (PBMT) on the bone repair process on defects filled with demineralized bovine bone (B) and fibrin sealant (T). The groups were BC (blood clot), BT (B + T), BCP (BC + PBMT), and BTP (B + T + PBMT). Microtomographically, BC and BCP presented a hypodense cavity with hyperdense regions adjacent to the border of the wound, with a slight increase at 42 days. BT and BTP presented discrete hyperdensing areas at the border and around the B particles. Quantitatively, BCP and BTP (16.96 ± 4.38; 17.37 ± 4.38) showed higher mean bone density volume in relation to BC and BT (14.42 ± 3.66; 13.44 ± 3.88). Histologically, BC and BCP presented deposition of immature bone at the periphery and at 42 days new bone tissue became lamellar with organized total collagen fibers. BT and BTP showed inflammatory infiltrate along the particles, but at 42 days, it was resolved, mainly in BTP. In the birefringence analysis, BT and BTP, the percentage of red birefringence increased (9.14% to 20.98% and 7.21% to 27.57%, respectively), but green birefringence was similar in relation to 14 days (3.3% to 3.5% and 3.5% to 4.2%, respectively). The number of osteocytes in the neoformed bone matrix proportionally reduced in all evaluated groups. Immunostaining of bone morphogenetic protein (BMP­2/4), osteocalcin (OCN), and vascular endothelial growth factor (VEGF) were higher in BCP and BTP when compared to the BC and BT groups (p < 0.05). An increased number of TRAP positive cells (tartrate resistant acid phosphatase) was observed in BT and BTP. We conclude that PBMT positively influenced the repair of bone defects filled with B and T.