RESUMO
Arteriovenous graft (AVG) failure continues to be a life-threatening problem in haemodialysis. Graft failure can occur if the implanted graft is not well-matched to the vasculature of the patient. Likewise, stenosis often develops at the vein-graft anastomosis, contributing to thrombosis and early graft failure. To address this clinical need, a novel ink formulation comprised of ACMO/TMPTA/TMETA for 3D printing a AVG was developed (ACMO-AVG), in which the printed AVG was biocompatible and did not induce cytotoxicity. The ease of customizing the ACMO-AVG according to different requirements was demonstrated. Furthermore, the AVG displayed similar mechanical properties to the commercially available arteriovenous ePTFE graft (ePTFE-AVG). Unlike ePTFE-AVG, the ACMO-AVG displayed excellent anti-fouling characteristics because no plasma protein adsorption and platelet adhesion were detected on the luminal surfaces after 2 h of incubation. Similarly, exposure to human endothelial cells and human vascular smooth muscle cells did not result in any cell detection on the surfaces of the ACMO-AVG. Thus, the present study demonstrates a newly developed 3D printing ink formulation that can be successfully 3D printed into a clinically applicable vascular access used for haemodialysis.
RESUMO
Herein, we report the synthesis of simple TPE/single amino acid conjugates, TPE-Ser and TPE-Asp with side-chains featuring functional groups that may provide an additional hydrogen bonding network for hydrogelation in aqueous medium. TPE-Ser, which has the lowest molecular weight, containing hydroxyl groups undergoes self-assembly into supramolecular hydrogels under physiological pH conditions. TPE-Asp with a carboxylic group side chain undergoes the self-assembly and hydrogelation processes under slightly acidic conditions (pH = 6.0). UV-vis, IR, PL and rheological studies clearly indicate the formation, stability and fluorescence properties of TPE-amino acid hydrogels. TEM micrographs of the hydrogels indicate that the compounds are self-assembled into a nanosheet morphology with random size and shape. Further, in vitro analysis of TPE-Ser and TPE-Asp with 3A6 cells shows that the compounds exhibit unique fluorescence signals in microcellular environments thus making them suitable candidates for bioimaging applications. Overall, these findings highlight the importance of the structure-hydrogelation relationship and provide new insights into the design of single amino-acid-based supramolecular hydrogels.
RESUMO
OBJECTIVES: When treating advanced HNSCC, a cisplatin-based systemic regimen benefit patient survival. However, chemoresistance will greatly reduce the effectiveness of this approach. The identification of molecules that contribute to cisplatin resistance may potentially improve the survival. Both HB-EGF and COX-2 have been reported to increase cisplatin-resistance. Here, we have focused on the regulation of HB-EGF/COX-2 and their roles in cisplatin resistance. MATERIALS AND METHODS: IHC staining was used to measure the expression levels of HB-EGF and COX-2 on the tissue microarray from 43 tissue samples of patients with advanced HNSCC. siRNA, western blot and qRT-PCR were used to dissect the regulation between EGF, Akt, COX-2, PGE2, and cisplatin sensitivity. The correlation between HB-EGF, COX2 and HNSCC progression was analyzed by the receiver operating characteristic (ROC) curve and Kaplan-Meier disease free survival. RESULTS: Patients of advanced HNSCC patients with increased HB-EGF and COX-2 expression have higher tumor recurrent rates that was related to cisplatin resistance. The resistance was mediated via an increased expression of HB-EGF and COX-2. The activation of Akt by either EGF or areca nut extract were able to upregulate COX-2, which would increase the expression of HB-EGF in a PGE2 dependent manner. Inhibition and knockdown of COX-2 resulted in a decrease in HB-EGF. In the tissue samples from HNSCC patients, there was a significant positive correlation between the expression of COX-2 and HB-EGF. CONCLUSION: Our results suggested that COX-2 and HB-EGF are important in development of HNSCC cisplatin resistance. These findings may help the development of new strategies for overcoming cisplatin resistance.
