The Effect of the Mechanical Properties of the 3D Printed Gelatin/ Hyaluronic Acid Scaffolds on hMSCs Differentiation Towards Chondrogenesis

BACKGROUND@#Tissue engineering, including 3D bioprinting, holds great promise as a therapeutic tool for repairing cartilage defects. Mesenchymal stem cells have the potential to treat various fields due to their ability to differentiate into different cell types. The biomimetic substrate, such as scaffolds and hydrogels, is a crucial factor that affects cell behavior, and the mechanical properties of the substrate have been shown to impact differentiation during incubation. In this study, we examine the effect of the mechanical properties of the 3D printed scaffolds, made using different concentrations of cross-linker, on hMSCs differentiation towards chondrogenesis. @*METHODS@#The 3D scaffold was fabricated using 3D bioprinting technology with gelatin/hyaluronic acid (HyA) biomaterial ink. Crosslinking was achieved by using different concentrations of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methlymorpholinium chloride n-hydrate (DMTMM), allowing for control of the scaffold’s mechanical properties. The printability and stability were also evaluated based on the concentration of DMTMM used. The effects of the gelatin/HyA scaffold on chondrogenic differentiation was analyzed by utilizing various concentrations of DMTMM. @*RESULTS@#The addition of HyA was found to improve the printability and stability of 3D printed gelatin/HyA scaffolds.The mechanical properties of the 3D gelatin/HyA scaffold could be regulated through the use of different concentrations of DMTMM cross-linker. In particular, the use of 0.25 mM DMTMM for crosslinking the 3D gelatin/HyA scaffold resulted in enhanced chondrocyte differentiation. @*CONCLUSION@#The mechanical properties of 3D printed gelatin/HyA scaffolds cross-linked using various concentrations of DMTMM can influence the differentiation of hMSCs into chondrocytes.

Effects of Fluvastatin on the Pharmacokinetics of Repaglinide: Possible Role of CYP3A4 and P-glycoprotein Inhibition by Fluvastatin

The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration(IC50) of 4.1 microM and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the AUC0-infinity of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions.

Enhanced local anesthetic action of mepivacaine from the bioadhesive gels

Mepivacaine, an amide-type local anesthetic, has been used to relieve local pain. Among the many drug delivery systems, transdermal drug delivery has some advantages, as it provides controlled drug delivery for an extended period of time. To develop new gel formulations that have suitable bioadhesion, the bioadhesive force of hydroxypropyl methylcellulose [HPMC] was assessed using an auto-peeling tester. The effect of drug concentration on drug release from 2% HPMC gel was studied using synthetic cellulose membrane at 37 +/- 0.5°C. The drug concentrations tested were 0.5, 1, 1.5, 2, and 2.5%. The effect of temperature on drug release from the 2% drug gel was evaluated at 27, 32, 37 and 42°C. To increase the skin permeation of mepivacaine from HPMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the mepivacaine-HPMC gels. The enhancing effect of the enhancer on drug permeation was then examined in the modified Keshary-Chien cell. For the efficacy study, the anesthetic action of the formulated mepivacaine gel containing enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. Among the various kinds of HPMC, HPMC-K100M gel showed the highest viscosity and bioadhesive force. As the viscosity of the HPMC gels increased, the bioadhesive forces increased. Increasing the drug concentration or temperature increased the drug release rate. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancement of permeation. Based on the area under the efficacy curve of the rat tail flick test curve, mepivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed prolonged and increased local anesthetic action compared to the control. For bioadhesive mepivacaine gels with enhanced local anesthetic action, mepivacaine gels containing penetration enhancer and vasoconstrictor could be developed with the bioadhesive polymer, HPMC

A Case of Mucinous Adenocarcinoma of Appendix Metastasis to Ovary / 대한산부인과학회잡지

Primary adenocarcinoma of appendix is a rare clinical entity that is virtually neverdiagnosed preoperatively.The first description was that of Berger in 1882 and this carcinoma was alwayssymptomatic causing a variant of acute appedicitis and palpable right lower quadrant mass. Thefrequency range between 0.08% to 0.5% and these tumors behave aggressively. The possibleroute of metastasize is mainly by peritoneal implantation and right-sided hemicolectomyis the best treatment.We experienced a case of mucinous adenocarcinoma of appendix metastasis to ovaryand we present this case with the brief review of literature.