Are hydroxyapatite-based biomaterials free of genotoxicity? A systematic review.

Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical characterization and biocompatibility. Generally, biocompatibility is analyzed through adhesion, proliferation, and differentiation assays. Fewer studies are looking for genotoxic events. Thus, although HA-based biomaterials are widely used as biomedical devices, there is a lack of literature regarding their genotoxicity. This systematic review was carried out following the PRISMA statement. Specific search strategies were developed and performed in four electronic databases (PubMed, Science Direct, Scopus, and Web of Science). The search used "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND genotoxicity OR genotoxic OR DNA damage" and "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND mutagenicity OR mutagenic OR DNA damage" as keywords and articles published from 2000 to 2022, after removing duplicate studies and apply include and exclusion criteria, 53 articles were identified and submitted to a qualitative descriptive analysis. Most of the assays were in vitro and most of the studies did not show genotoxicity. In fact, a protective effect was observed for hydroxyapatites. Only 20 out of 71 tests performed were positive for genotoxicity. However, no point mutation-related mutagenicity was observed. As the genotoxicity of HA-based biomaterials observed was correlated with its nanostructured forms as needles or rods, it is important to follow their effect in chronic exposure to guarantee safe usage in humans.

A Blend Consisting of Agaran from Seaweed Gracilaria birdiae and Chromium Picolinate Is a Better Antioxidant Agent than These Two Compounds Alone.

A blend refers to the combination of two or more components to achieve properties that are superior to those found in the individual products used for their production. Gracilaria birdiae agaran (SPGb) and chromium picolinate (ChrPic) are both antioxidant agents. However, there is no documentation of blends that incorporate agarans and ChrPic. Hence, the objective of this study was to generate blends containing SPGb and ChrPic that exhibit enhanced antioxidant activity compared to SPGb or ChrPic alone. ChrPic was commercially acquired, while SPGb was extracted from the seaweed. Five blends (B1; B2; B3; B4; B5) were produced, and tests indicated B5 as the best antioxidant blend. B5 was not cytotoxic or genotoxic. H2O2 (0.6 mM) induced toxicity in fibroblasts (3T3), and this effect was abolished by B5 (0.05 mg·mL-1); neither ChrPic nor SPGb showed this effect. The cells also showed no signs of toxicity when exposed to H2O2 after being incubated with B5 and ChrPic for 24 h. In another experiment, cells were incubated with H2O2 and later exposed to SPGb, ChrPic, or B5. Again, SPGb was not effective, while cells exposed to ChrPic and B5 reduced MTT by 100%. The data demonstrated that B5 has activity superior to SPGb and ChrPic and points to B5 as a product to be used in future in vivo tests to confirm its antioxidant action. It may also be indicated as a possible nutraceutical agent.

Prospecting in silico antibacterial activity of a peptide from trypsin inhibitor isolated from tamarind seed.

Bacterial infections have become a global concern, stimulating the growing demand for natural and biologically safe therapeutic agents with antibacterial action. This study was evaluated the genotoxicity of the trypsin inhibitor isolated from tamarind seeds (TTI) and the antibacterial effect of TTI theoric model, number 56, and conformation number 287 (TTIp 56/287) and derived peptides in silico. TTI (0.3 and 0.6 mg.mL-1) did not cause genotoxicity in cells (p > 0.05). In silico, a greater interaction of TTIp 56/287 with the Gram-positive membrane (GP) was observed, with an interaction potential energy (IPE) of -1094.97 kcal.mol-1. In the TTIp 56/287-GP interaction, the Arginine, Threonine (Thr), and Lysine residues presented lower IPE. In molecular dynamics (MD), Peptidotrychyme59 (TVSQTPIDIPIGLPVR) showed an IPE of -518.08 kcal.mol-1 with the membrane of GP bacteria, and the Thr and Arginine residues showed the greater IPE. The results highlight new perspectives on TTI and its derived peptides antibacterial activity.

Sulfated Glucan from the Green Seaweed Caulerpa sertularioides Inhibits Adipogenesis through Suppression of Adipogenic and Lipogenic Key Factors.

Sulfated polysaccharides (SPS) from seaweeds have great biochemical and biotechnological potential. This study aimed to investigate the effect of SPS isolated from the seaweed Caulerpa sertularioides on adipogenic differentiation as a possible alternative treatment for obesity. The SPS-rich extract from the seaweed C. sertularioides was fractioned into three SPS-rich fractions (F0.5; F0.9; and F1.8) chemically characterized. Among these four samples, only F0.9 showed a significant inhibitory effect on adipogenesis of 3T3-L1 preadipocytes. Ten SPS-rich fractions were isolated from F0.9 through ion-exchange chromatography. However, only the fraction (CS0.2) containing a sulfated glucan was able to inhibit adipogenesis. CS0.2 reduces lipid accumulation and inhibits the expression of key adipogenic (PPARγ, C/EBPß, and C/EBPα) and lipogenic markers (SREBP-1c, Fabp4, and CD36). The data points to the potential of sulfated glucan from C. sertularioides for the development of functional approaches in obesity management.

Role of sulfated polysaccharides from seaweeds in bone regeneration: A systematic review.

Studies on the effect of sulfated polysaccharides from seaweed on bone regeneration have increased in recent years. However, there is no consensus on how to use them and their real effectiveness in that process. Thereby, we carried out a systematic review to answer the question "Do the sulfated polysaccharides from seaweeds promote osteogenesis?". Searches were performed in Pubmed, Scopus, and Web of Knowledge databases. A total of 599 articles were selected, resulting in 14 eligible studies. Results showed that the sulfated polysaccharides from seaweeds increase the osteogenic markers evaluated. Nevertheless, due to the lack of standardization on protocols used, the results should be cautiously interpreted. In addition, studies using animal models are still scarce, and the results with cellular models cannot always be extrapolated to systems that are more complex. Despite the study limitations, the use of sulfated polysaccharides appears to promote in vitro osteogenesis and enhance bone regeneration.

Nanoencapsulation of buriti oil (Mauritia flexuosa L.f.) in porcine gelatin enhances the antioxidant potential and improves the effect on the antibiotic activity modulation.

The present study evaluated the cytotoxicity, antioxidant potential, and antimicrobial effect on the antibiotic activity modulation of gelatin nanoparticles containing buriti oil (OPG). The cytotoxicity analysis was performed on Chinese Hamster Ovary Cells (CHO) using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. The antioxidant potential of buriti oil and OPG was determined by total antioxidant capacity, reducing power, and the ABTS (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) test. The modulating antimicrobial activity was evaluated by determining the minimum inhibitory concentration (MIC) concentration against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, gentamicin and norflaxacillin. The nanoformulation of OPG did not show a cytotoxic effect on CHO cells and had a higher antioxidant potential than free buriti oil (p<0.05). The combination of antibiotics with free buriti oil and OPG was more efficient in inhibiting E. coli and P. aeruginosa than isolated norfloxacillin and gentamicin (p<0.05). Regarding the inhibition of S. aureus, OPG in combination with norfloxacillin reduced MIC by 50%. Nanoencapsulation was a viable alternative to enhance functionality and adding commercial value to buriti oil.

Genotoxicity and osteogenic potential of sulfated polysaccharides from Caulerpa prolifera seaweed.

Marine algae are sources of novel bioactive molecules and present a great potential for biotechnological and biomedical applications. Although green algae are the least studied type of seaweed, several of their biological activities have already been described. Here, we investigated the osteogenic potential of Sulfated Polysaccharide (SP)-enriched samples extracted from the green seaweed Caulerpa prolifera on human mesenchymal stem cells isolated from Wharton jelly (hMSC-WJ). In addition, the potential genotoxicity of these SPs was determined by cytokinesis-block micronucleus (CBMN) assay. SP-enriched samples did not show significant cytotoxicity towards hMSCs-WJ at a concentration of up to 10µg/mL, and after 72h of exposure. SP enrichment also significantly increased alkaline phosphatase (ALP) activity, promoting calcium accumulation in the extracellular matrix. Among the SP-enriched samples, the CP0.5 subfraction (at 5µg/mL) presented the most promising results. In this sample, ALP activity was increased approximately by 60%, and calcium accumulation was approximately 6-fold above the negative control, indicating high osteogenic potential. This subfraction also proved to be non-genotoxic, according to the CBMN assay, as it did not induce micronuclei. The results of this study highlight, for the first time, the potential of these SPs for the development of new therapies for bone regeneration.