In Vitro Cytotoxicity Evaluation of Highly Absorbent Foam Dressings Based on Silver Zirconium Phosphate via IC50 Value

In this study, we, for the first time, tried to apply IC50 values (inhibitory concentration estimated to affect the endpoint in question by 50%) in the MTT colorimetric assay to investigate the cytotoxic effects of highly absorbent foam dressings based on silver zirconium phosphate, a newly nano-based matrix. Our results showed that silver released from dressings based on silver zirconium phosphate attributed mainly to highly cytotoxic to L929 cells cultured with MEM containing 10% fetal bovine serum. In addition, we have also compared the IC50 values among different dilutions of AgNO3 solution, silver based dressing extracts and material reference control (ZDEC) extracts using the optimized MTT assay, along with characterizing the silver content in the dressing extracts using atomic absorption spectroscopy. Results have shown that the IC50 values of AgNO50 solution, silver based dressing extracts and ZDEC extracts are 3.5 μg/mL, 3.8 μg/mL and 8.4%, respectively. And there exist some good agreements between qualitative and quantitative evaluation method as well. In conclusion, our study has led to the view that the IC50 value is a promising quantitative index for screening cytotoxicity with regard to silver based dressings.

ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes

Toll-like receptors （TLRs） are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbial recognition by TLRs and subsequent TLR-triggered cytokine production are deregulated. Activating transcription factor 4 （ATF4）, a member of the ATF/CREB transcription factor family, is an important factor that participates in several pathophysiological processes. In this report, we found that ATF4 is also involved in the TLR-mediated innate immune response, which participates in TLR4 signal transduction and mediates the secretion of a variety of cytokines. We observed that ATF4 is activated and translocates to the nucleus following l ipopolysaccharide （LPS） stimulation via the TLR4-MyD88-dependent pathway. Additionally, a cytokine array assay showed that some key inflammatory cytokines, such as I L-6, I L-8 and RANTES, are positively regulated by ATF4. We also demonstrate that c-Jun directly binds to ATF4, thereby promoting the secretion of inflammatory cytokines. Taken together, these results indicate that ATF4 acts as a positive regulator in TLR4-triggered cytokine production.

A novel method for evaluating the dynamic biocompatibility of degradable biomaterials based on real-time cell analysis

Degradable biomaterials have emerged as a promising type of medical materials because of their unique advantages of biocompatibility,biodegradability and biosafety.Owing to their bioabsorbable and biocompatible properties,magnesium-based biomaterials are considered as ideal degradable medical implants.However,the rapid corrosion of magnesium-based materials not only limits their clinical application but also necessitates a more specific biological evaluation system and biosafety standard.In this study,extracts of pure Mg and its calcium alloy were prepared using different media based on ISO 10993:12;the Mg^2+ concentration and osmolality of each extract were measured.The biocompatibility was investigated using the MTT assay and xCELLigence real-time cell analysis(RTCA).Cytotoxicity tests were conducted with L929,MG-63 and human umbilical vein endothelial cell lines.The results of the RTCA highly matched with those of the MTT assay and revealed the different dynamic modes of the cytotoxic process,which are related to the differences in the tested cell lines,Mg-based materials and dilution rates of extracts.This study provides an insight on the biocompatibility of biodegradable materials from the perspective of cytotoxic dynamics and suggests the applicability of RTCA for the cytotoxic evaluation of degradable biomaterials.

Evaluation of repeated exposure systemic toxicity test of PVC with new plasticizer on rats via dual parenteral routes

Systemic toxicity caused by repeated exposure to both polar and nonpolar leachables of di(2-ethylhexyl)-1,2-cyclohexane plasticized polyvinyl chloride(PVC)was evaluated with dual routes of parenteral administration method on rats in the study.Experimental group and control group were designed by researchers.Tail intravenous injection with 0.9%sodium chloride injection extracts and intraperitoneal injection with corn oil extracts were conducted to the experimental rats while tail intravenous injection with 0.9%sodium chloride Injection and intraperitoneal injection with corn oil were conducted to the control rats.After 14 days,blood specimens were collected for clinical pathology(hematology and clinical chemistry)analysis.Selected organs were weighed and a histopathological examination was conducted.As a result,compared with the control animals,there were no toxicity-related changes on the parameters above.The results show that the rats do not show obvious systemic toxicity reaction caused by repeated exposure with dual routes of parenteral administration method on rats after administration with both polar and nonpolar exacts of di(2-ethylhexyl)-1,2-cyclohexane plasticized PVC simultaneously up for 14 days.