Avaliação do uso do biopolímero heterólogo de fibrina e cerâmica sintética de hidroxiapatita/fosfato tricálcico, associado ou não à terapia por fotobiomodulação, no reparo de defeitos ósseos

Extensive bone loss resulting from fractures or tumor resection poses a challenge for tissue bioengineering areas, in the search for morphological and functional recomposition in a shorter period. The joint use of low-level laser (currently called photobiomodulation therapy - PBM) and bioproducts provides new horizons for tissue repair with a greater chance of success, such as, for example, biocomplexes consisting of fibrin sealant and particulate biomaterials. Objectives: In article 1, the systematic review aimed to evaluate the relationship between PBM and the use of fibrin compounds, referring to the results of previous studies published in PubMed/MEDLINE, Scopus and Web of Science databases and, in article 2, to evaluate the grafting of hydroxyapatite/tricalcium phosphate (BCP) ceramic biomaterial (B) together with the heterologous fibrin biopolymer (FB) and with photobiomodulation (PBM) in the repair process of bone defects. Materials and methods: In article 1, the descriptors fibrin AND low-level laser therapy and fibrin AND photobiomodulation were used, without restriction on publication time. In article 2, fifty-six rats were randomly divided into four groups of seven animals each: the biomaterial group (G1/B), the biomaterial plus FB group (G2/BFB); the biomaterial plus PBM group (G3/B + PBM), and the biomaterial plus FB plus PBM group (G4/BFB + PBM). After anesthesia, a critical defect was performed in the center of the rats parietal bones, then filled and treated according to their respective groups. The rats were euthanized at 14 and 42 postoperative days. Results: In article 1, the bibliographic search found 44 articles in PubMed/MEDLINE, of which 26 were excluded due to duplicity or being outside the eligibility criteria. We also found 40 articles in Web of Science and selected 1 article, 152 articles in Scopus and no article selected, totaling 19 articles for qualitative analysis. The fibrin type most used in combination with PBM was fibrin sealant, mainly heterologous, followed by PRF or L-PRF. In PBM, the gallium-aluminum-arsenide (GaAlAs) laser prevailed, with a wavelength of 830 nm, followed by 810 nm. Among the preclinical studies, the most researched association of fibrin and PBM was the use of fibrin sealants in bone or nerve injuries; in clinical studies, the association of PBM with medication-related treatments osteonecrosis of the jaw (MRONJ). In article 2, in the comparison between the groups, in the two experimental periods (14 and 42 days), in relation to the percentage of formation of new bone tissue, a significant difference was found between all groups (G1/B (5.42 ± 1.12; 21.49 ± 4.74), G2/BFB (5.00 ± 0.94; 21.77 ± 2.83), G3/B + PBM (12.65 ± 1.78; 29.29 ± 2.93), and G4/BFB + PBM (12.65 ± 2.32; 31.38 ± 2.89)). Conclusion: The literature consulted on PBM, associated with fibrin compounds, scores positive results in several areas of tissue bioengineering, mainly in the recovery of extensive bone loss and peripheral nerve injuries. The reproducibility of research in this area presents problems, due to the numerous protocols that are used and not always fully described in scientific articles. The interaction of the biocomplex composed of Hydroxyapatite/Tricalcium Phosphate Ceramic and Fibrin Biopolymer was potentially effective in the reconstruction of critical bone defects in the calvaria of rats, because the combined use generated perspectives of faster regeneration than when biomaterials and biopharmaceuticals are used separately.As extensas perdas ósseas, decorrentes de fraturas ou ressecção de tumores, ocasionam um desafio para as áreas de bioengenharia tecidual, na busca da recomposição morfológica e funcional, em menor espaço de tempo. O uso conjunto do laser de baixa potência (atualmente denominada terapia de fotobiomodulação - FBM) e bioprodutos fornece novos horizontes para reparação tecidual com maior chance de sucesso como, por exemplo, os biocomplexos constituídos por selante de fibrina e biomateriais particulados. Objetivos: No artigo 1, a revisão sistemática teve como objetivo avaliar a relação entre FBM e o uso de compostos de fibrina, referindo-se aos resultados de estudos anteriores publicados nas bases de dados PubMed/MEDLINE, Scopus e Web of Science e, no artigo 2, avaliar o enxerto do biomaterial cerâmico de hidroxiapatita/fosfato tricálcico (BCP) (B) juntamente com o biopolímero heterólogo de fibrina (FB) e com fotobiomodulação (PBM) no processo de reparação de defeitos ósseos. Materiais e métodos: No artigo 1, foram utilizados os descritores fibrin AND low-level laser therapy e fibrin AND photobiomodulation, sem restrição de tempo de publicação. No artigo 2, cinquenta e seis ratos foram divididos aleatoriamente em quatro grupos de sete animais cada: grupo biomaterial (G1/B), grupo biomaterial + FB (G2/BFB); grupo biomaterial + PBM (G3/B + PBM) e o grupo biomaterial + FB + PBM (G4/BFB + PBM). Após a anestesia, um defeito crítico foi feito no centro dos ossos parietais, preenchido e tratado de acordo com seus respectivos grupos. Os ratos foram eutanasiados aos 14 e 42 dias de pós-operatório. Resultados: No artigo 1, A busca bibliográfica encontrou 44 artigos no PubMed/MEDLINE, dos quais 26 foram excluídos por duplicidade ou por estarem fora dos critérios de elegibilidade. Também encontramos 40 artigos na Web of Science e selecionamos 1 artigo, 152 artigos na Scopus e nenhum artigo selecionado, totalizando 19 artigos para análise qualitativa. O tipo de fibrina mais utilizado em combinação com FBM foi o selante de fibrina, principalmente heterólogo, seguido de PRF ou L-PRF. No FBM, prevaleceu o laser de arseneto de gálio-alumínio, com comprimento de onda de 830 nm e 810 nm. Entre os pré-clínicos, a associação de fibrina e FBM mais estudada foi o uso de selantes de fibrina em lesões ósseas ou nervosas; em estudos clínicos, a associação de FBM com tratamentos medicamentosos relacionados à osteonecrose da mandíbula. No artigo 2, na comparação entre os grupos, nos dois períodos experimentais (14 e 42 dias), em relação ao percentual de formação de tecido ósseo novo, foi encontrada diferença significativa entre todos os grupos (G1/B (5,42 ± 1,12; 21,49 ± 4,74), G2/BFB (5,00 ± 0,94; 21,77 ± 2,83), G3/B + PBM (12,65 ± 1,78; 29,29 ± 2,93) e G4/BFB + PBM (12,65 ± 2,32; 31,38 ± 2,89)). Conclusão: A literatura consultada sobre FBM, associada a compostos de fibrina, apresenta resultados positivos em diversas áreas da bioengenharia tecidual, principalmente na recuperação de extensas perdas ósseas e lesões de nervos periféricos. A reprodutibilidade das pesquisas nessa área apresenta problemas, devido aos inúmeros protocolos que são utilizados e nem sempre totalmente descritos em artigos científicos. A interação do biocomplexo composto por Cerâmica de Hidroxiapatita/Fosfato Tricálcico e Biopolímero de Fibrina foi potencialmente eficaz na reconstrução de defeitos ósseos críticos na calvária de ratos, pois o uso combinado gerou perspectivas de regeneração mais rápida do que quando biomateriais e biofármacos são utilizados separadamente

Effects of a Biocomplex Formed by Two Scaffold Biomaterials, Hydroxyapatite/Tricalcium Phosphate Ceramic and Fibrin Biopolymer, with Photobiomodulation, on Bone Repair

There are several treatment methods available for bone repair, although the effectiveness becomes limited in cases of large defects. The objective of this pre-clinical protocol was to evaluate the grafting of hydroxyapatite/tricalcium phosphate (BCP) ceramic biomaterial (B; QualyBone BCP®, QualyLive, Amadora, Portugal) together with the heterologous fibrin biopolymer (FB; CEVAP/UNESP Botucatu, Brazil) and with photobiomodulation (PBM; Laserpulse®, Ibramed, Amparo, Brazil) in the repair process of bone defects. Fifty-six rats were randomly divided into four groups of seven animals each: the biomaterial group (G1/B), the biomaterial plus FB group (G2/BFB); the biomaterial plus PBM group (G3/B + PBM), and the biomaterial plus FB plus PBM group (G4/BFB + PBM). After anesthesia, a critical defect was performed in the center of the rats’ parietal bones, then filled and treated according to their respective groups. The rats were euthanized at 14 and 42 postoperative days. Histomorphologically, at 42 days, the G4/BFB + PBM group showed a more advanced maturation transition, with more organized and mature bone areas forming concentric lamellae. A birefringence analysis of collagen fibers also showed a more advanced degree of maturation for the G4/BFB + PBM group. In the comparison between the groups, in the two experimental periods (14 and 42 days), in relation to the percentage of formation of new bone tissue, a significant difference was found between all groups (G1/B (5.42 ± 1.12; 21.49 ± 4.74), G2/BFB (5.00 ± 0.94; 21.77 ± 2.83), G3/B + PBM (12.65 ± 1.78; 29.29 ± 2.93), and G4/BFB + PBM (12.65 ± 2.32; 31.38 ± 2.89)). It was concluded that the use of PBM with low-level laser therapy (LLLT) positively interfered in the repair process of bone defects previously filled with the biocomplex formed by the heterologous fibrin biopolymer associated with the synthetic ceramic of hydroxyapatite and tricalcium phosphate

Biological Properties and Antimicrobial Potential of Cocoa and Its Effects on Systemic and Oral Health

Cocoa is considered a functional food because it is a natural source of macro- and micronutrients. Thus, cocoa is rich in vitamins, minerals, fiber, fatty acids, methylxanthines and flavonoids. In addition to favoring the metabolism of lipids and carbohydrates, the bioactive components of cocoa can have an antioxidant, anti-inflammatory and antimicrobial effect, providing numerous benefits for health. This literature review presents an overview of the effects of cocoa, fruit of the Theobroma cacao tree, on systemic and oral health. Several studies report that cocoa intake may contribute to the prevention of cardiovascular, neurodegenerative, immunological, inflammatory, metabolic and bone diseases, in addition to reducing the risk of vascular alterations and cognitive dysfunctions. On oral health, in vitro studies have shown that cocoa extract exerted an inhibitory effect on the growth, adherence and metabolism of cariogenic and periodontopathogenic bacteria, also inhibiting acid production, glycosyltransferase enzyme activity and the synthesis of insoluble polysaccharides. Additionally, administration of cocoa extract reduced biofilm accumulation and caries development in animals infected with cariogenic species. Clinical studies also reported that the use of mouthwashes containing cocoa extract reduced Streptococcus mutans counts in saliva and dental biofilm formation. In short, these studies highlight the nutritional value of cocoa, considering its clinical applicability, stability and economic accessibility

Clinical potential in modern medicine of fibrin glues as drug delivery system

In an attempt to achieve greater therapeutic efficiency of products, especially in the pharmacological area such as drugs in general, the drug delivery system that controls the distribution of substances through macromolecular carriers has been developed with the primary objective of optimizing their delivery to target locations [1].</p

Evaluation of the Use of an Inorganic Bone Matrix in the Repair of Bone Defects in Rats Submitted to Experimental Alcoholism

To assess the effects of chronic alcoholism on the repair of bone defects associated with xenograft. Forty male rats were distributed in: control group (CG, n = 20) and experimental group (EG, n = 20), which received 25% ethanol ad libitum after a period of adaptation. After 90 days of liquid diet, the rats were submitted to 5.0-mm bilateral craniotomy on the parietal bones, subdividing into groups: CCG (control group that received only water with liquid diet and the defect was filled with blood clot), BCG (control group that received only water with liquid diet and the defect was filled with biomaterial), CEG (alcoholic group that received only ethanol solution 25% v/v with liquid diet and the defect was filled with blood clot), and BEG (alcoholic group that received only ethanol solution 25% v/v with liquid diet and the defect was filled with biomaterial). In the analysis of body mass, the drunk animals presented the lowest averages in relation to non-drunk animals during the experimental period. Histomorphologically all groups presented bone formation restricted to the defect margins at 60 days, with bone islets adjacent to the BCG biomaterial particles. CEG showed significant difference compared to BEG only at 40 days (17.42 &plusmn; 2.78 vs. 9.59 &plusmn; 4.59, respectively). In the birefringence analysis, in early periods all groups showed red-orange birefringence turning greenish-yellow at the end of the experiment. The results provided that, regardless of clinical condition, i.e., alcoholic or non-alcoholic, in the final period of the experiment, the process of bone defect recomposition was similar with the use of xenograft or only clot

Photobiomodulation Therapy as a Possible New Approach in COVID-19: A Systematic Review

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

Effects of Therapy with Fibrin Glue combined with Mesenchymal Stem Cells (MSCs) on Bone Regeneration: A Systematic Review

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