Cell therapy strategies using mesenchymal stem cells (MSCs) carried in fibrin glue have shown promising results in regenerative medicine. MSCs are crucial for tissue healing because they have angiogenic, anti-apoptotic and immunomodulatory properties, in addition to the ability to differentiate into several specialized cell lines. Fibrin sealant or fibrin glue is a natural polymer involved in the coagulation process. Fibrin glue provides a temporary structure that favors angiogenesis, extracellular matrix deposition and cell-matrix interactions. Additionally, fibrin glue maintains the local and paracrine functions of MSCs, providing tissue regeneration through less invasive clinical procedures. Thus, the objective of this systematic review was to assess the potential of fibrin glue combined with MSCs in bone or cartilage regeneration. The bibliographic search was performed in the PubMed/MEDLINE, LILACS and Embase databases, using the descriptors (“fibrin sealant” OR “fibrin glue”) AND “stem cells” AND “bone regeneration”, considering articles published until 2021. In this case, 12 preclinical and five clinical studies were selected to compose this review, according to the eligibility criteria. In preclinical studies, fibrin glue loaded with MSCs, alone or associated with bone substitute, significantly favored bone defects regeneration compared to scaffold without cells. Similarly, fibrin glue loaded with MSCs presented considerable potential to regenerate joint cartilage injuries and multiple bone fractures, with significant improvement in clinical parameters and absence of postoperative complications. Therefore, there is clear evidence in the literature that fibrin glue loaded with MSCs, alone or combined with bone substitute, is a promising strategy for treating lesions in bone or cartilaginous tissue.

COVID-19 is a viral disease characterized as a pandemic by the World Health Organization in March 2020. Since then, researchers from all over the world have been looking for ways to fight this disease. Many cases of complications arise from insufficient immune responses due to low immunity, with intense release of pro-inflammatory cytokines that can damage the structure of organs such as the lung. Thus, the hypothesis arises that photobiomodulation therapy (PBMT) with the use of a low-level laser (LLLT) may be an ally approach to patients with COVID-19 since it is effective for increasing immunity, helping tissue repair, and reducing pro-inflammatory cytokines. This systematic review was performed with the use of PubMed/MEDLINE, Web of Science, Scopus and Google Scholar databases with the following keywords: “low-level laser therapy OR photobiomodulation therapy AND COVID-19”. The inclusion criteria were complete articles published from January 2020 to January 2021 in English. The exclusion criteria were other languages, editorials, reviews, brief communications, letters to the editor, comments, conference abstracts, and articles that did not provide the full text. The bibliographic search found 18 articles in the Pubmed/MEDLINE database, 118 articles on the Web of Science, 23 articles on Scopus, and 853 articles on Google Scholar. Ten articles were included for qualitative synthesis, of which four commentary articles discussed the pathogenesis and the effect of PBMT in COVID-19. Two in vitro and lab experiments showed the effect of PBMT on prevention of thrombosis and positive results in wound healing during viral infection, using the intravascular irradiation (ILIB) associated with Phthalomethyl D. Two case reports showed PBMT improved the respiratory indexes, radiological findings, and inflammatory markers in severe COVID-19 patients. One case series reported the clinical improvement after PBMT on 14 acute COVID-19 patients, rehabilitation on 24 patients, and as a preventive treatment on 70 people. One clinical trial of 30 patients with severe COVID-19 who require invasive mechanical ventilation, showed PBMT-static magnetic field was not statistically different from placebo for the length of stay in the Intensive Care Unit, but improved diaphragm muscle function and ventilation and decreased the inflammatory markers. This review suggests that PBMT may have a positive role in treatment of COVID-19. Still, the necessity for more clinical trials remains in this field and there is not sufficient research evidence regarding the effects of PBMT and COVID-19 disease, and there is a large gap.

Peripheral nerve injuries impair the patient’s functional capacity, including those occurring in the facial nerve, which require effective medical treatment. Thus, we investigated the use of heterologous fibrin biopolymer (HFB) in the repair of the buccal branch of the facial nerve (BBFN) associated with photobiomodulation (PBM), using a low-level laser (LLLT), analyzing the effects on axons, muscles facials, and functional recovery. This experimental study used twenty-one rats randomly divided into three groups of seven animals, using the BBFN bilaterally (the left nerve was used for LLLT): Control group—normal and laser (CGn and CGl); Denervated group—normal and laser (DGn and DGl); Experimental Repair Group—normal and laser (ERGn and ERGl). The photobiomodulation protocol began in the immediate postoperative period and continued for 5 weeks with a weekly application. After 6 weeks of the experiment, the BBFN and the perioral muscles were collected. A significant difference (p < 0.05) was observed in nerve fiber diameter (7.10 ± 0.25 µm and 8.00 ± 0.36 µm, respectively) and axon diameter (3.31 ± 0.19 µm and 4.07 ± 0.27 µm, respectively) between ERGn and ERGl. In the area of muscle fibers, ERGl was similar to GC. In the functional analysis, the ERGn and the ERGI (4.38 ± 0.10) and the ERGI (4.56 ± 0.11) showed parameters of normality. We show that HFB and PBM had positive effects on the morphological and functional stimulation of the buccal branch of the facial nerve, being an alternative and favorable for the regeneration of severe injuries.

The association of scaffolds to repair extensive bone defects can contribute to their evolution and morphophysiological recomposition. The incorporation of particulate biomaterials into three-dimensional fibrin bioproducts together with photobiomodulation therapy (PBM) has potential and can improve regenerative medicine procedures. The objective of this experiment was to evaluate the effects of PBM therapy on critical size defects filled with xenogenic bone substitute associated with fibrin biopolymer. A critical defect of 8 mm was performed in 36 Wistar male adult rats that were divided into four groups. Groups BC and BC-PBM were defined as controls with defects filled by a clot (without or with PBM, respectively) and groups XS and XS-PBM that comprised those filled with biocomplex Bio-Oss^TM in association with fibrin biopolymer. PBM was applied immediately after the surgery and three times a week every other day, with the parameters: wavelength of 830 nm, energy density 6.2 J/cm², output power 30 mW, beam area of 0.116 cm², irradiance 0.258,62 W/cm², energy/point 0.72 J, total energy 2.88 J. Fourteen and 42 days after the surgery, animals were euthanatized and subjected to microtomography, qualitative and quantitative histological analysis. The BC-PBM and XS-PBM groups had a similar evolution in the tissue repair process, with a higher density of the volume of new formed bone in relation to the groups without PBM (p = 0.04086; p = 0.07093, respectively). Intense vascular proliferation and bone deposition around the biomaterial particles were observed in the animals of the groups in which biocomplex was applied (XS and XS-PBM). PBM therapy allowed an improvement in the formation of new bone, with a more organized deposition of collagen fibers in the defect area. Biocomplex favored the insertion and permanence of the particulate material in bone defects, creating a favorable microenvironment for accelerate repair process.

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: BC_L (blood clot + laser); HF; HF_L; PHF (P+HF); PHF_L (P+HF+L). Microtomographically, bone volume (BV) at 14 days, was higher in the PHF and PHF_L groups (10.45 ± 3.31 mm³ and 9.94 ± 1.51 mm³), significantly increasing in the BC_L, HF_L and PHF_L 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.