Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in seeds, grains, tea, coffee, wine, chocolate, cocoa, vegetables and, mainly, in citrus fruits. Neohesperidin, hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory and antioxidant potential. Neohesperidin, in the form of neohesperidin dihydrochalcone (NHDC), also has dietary properties as a sweetener. In general, these flavanones have been investigated as a strategy to control bone diseases, such as osteoporosis and osteoarthritis. In this literature review, we compiled studies that investigated the effects of neohesperidin, hesperidin and its aglycone, hesperetin, on bone health. In vitro studies showed that these flavanones exerted an antiosteoclastic and anti- inflammatory effects, inhibiting the expression of osteoclastic markers and reducing the levels of reactive oxygen species, proinflammatory cytokines and matrix metalloproteinase levels. Similarly, such studies favored the osteogenic potential of preosteoblastic cells and induced the overexpression of osteogenic markers. In vivo, these flavanones favored the regeneration of bone defects and minimized inflammation in arthritis- and periodontitis-induced models. Additionally, they exerted a significant anticatabolic effect in ovariectomy models, reducing trabecular bone loss and increasing bone mineral density. Although research should advance to the clinical field, these flavanones may have therapeutic potential for controlling the progression of metabolic, autoimmune or inflammatory bone diseases.

Carbohydrates have a dietary role, but excessive consumption of high-calorie sugars can contribute to an increased incidence of metabolic diseases and dental caries. Recently, carbohydrates with sweetening properties and low caloric value, such as D-tagatose, have been investigated as alternative sugars. D-tagatose is a rare sugar that has nutritional and functional properties of great interest for health. This literature review presents an approach to the biological effects of D-tagatose, emphasizing its benefits for oral health. Studies report that D-tagatose has antioxidant and prebiotic effects, low digestibility, reduced glycemic and insulinemic responses, and the potential to improve the lipid profile, constituting an alternative for diabetes mellitus and obesity. It can also be observed that D-tagatose has an antioxidant action, favoring the elimination of free radicals and, consequently, causing a reduction in cellular oxidative stress. Furthermore, it also has antibacterial potential against oral species. Regarding oral health, studies have shown that D-tagatose efficiently reversed bacterial coaggregations, including periodontopathogenic species, and impaired the activity and growth of cariogenic bacteria, such as S. mutans. D-tagatose significantly inhibited biofilm formation, pH decrease and insoluble glucan synthesis in S. mutans cultures. Salivary S. mutans counts were also significantly reduced by the consumption of chewing gum containing D-tagatose and xylitol. In addition, there is evidence that tagatose is effective as an air-polishing powder for biofilm decontamination. The literature indicates that D-tagatose can contribute to the prevention of systemic diseases, also constituting a promising agent to improve oral health.

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.

Fibrin, derived from proteins involved in blood clotting (fibrinogen and thrombin), is a biopolymer with different applications in the health area since it has hemostasis, biocompatible and three-dimensional physical structure properties, and can be used as scaffolds in tissue regeneration or drug delivery system for cells and/or growth factors. Fibrin alone or together with other biomaterials, has been indicated for use as a biological support to promote the regeneration of stem cells, bone, peripheral nerves, and other injured tissues. In its diversity of forms of application and constitution, there are platelet-rich fibrin (PRF), Leukocyte- and platelet-rich fibrin (L-PRF), fibrin glue or fibrin sealant, and hydrogels. In order to increase fibrin properties, adjuvant therapies can be combined to favor tissue repair, such as photobiomodulation (PBM), by low-level laser therapy (LLLT) or LEDs (Light Emitting Diode). Therefore, this 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. The descriptors “fibrin AND low-level laser therapy” and “fibrin AND photobiomodulation” were used, without restriction on publication time. 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). Therefore, there is scientific evidence of the contribution of PBM on fibrin composites, constituting a supporting therapy that acts by stimulating cell activity, angiogenesis, osteoblast activation, axonal growth, anti-inflammatory and anti-edema action, increased collagen synthesis and its maturation, as well as biomolecules.

The use of low-level laser therapy (LLLT) with biomodulatory effects on biological tissues, currently called photobiomodulation therapy (PBMT), assists in healing and reduces inflammation. The application of biomaterials has emerged in bone reconstructive surgery, especially the use of bovine bone due to its biocompatibility. Due to the many benefits related to the use of PBMT and bovine bones, the aim of this research was to review the literature to verify the relationship between PBMT and the application of bovine bone in bone reconstruction surgeries. We chose the PubMed/MEDLINE, Web of Science, and Scopus databases for the search by matching the keywords: “Bovine bone AND low-level laser therapy”, “Bovine bone AND photobiomodulation therapy”, “Xenograft AND low-level laser therapy”, and “Xenograft AND photobiomodulation therapy”. The initial search of the three databases retrieved 240 articles, 18 of which met all inclusion criteria. In the studies concerning animals (17 in total), there was evidence of PBMT assisting in biomaterial-related conduction, formation of new bone, bone healing, immunomarker expression, increasing collagen fibers, and local inflammation reduction. However, the results disagreed with regard to the resorption of biomaterial particles. The only human study showed that PBMT with bovine bone was effective for periodontal regeneration. It was concluded that PBMT assists the process in bone reconstruction when associated with bovine bone, despite divergences between applied protocols.

Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. Thus, the aim of this systematic review was to evaluate the potential of fibrin glue combined with MSCs in nerve regeneration. The bibliographic search was performed in the PubMed/MEDLINE, Web of Science and Embase databases, using the descriptors (“fibrin sealant” OR “fibrin glue”) AND “stem cells” AND “nerve regeneration”, considering articles published until 2021. To compose this review, 13 in vivo studies were selected, according to the eligibility criteria. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. This systematic review showed clear evidence that fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.