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Acta biomaterialia (1)
Dadsetan, Mahrokh (2)
Ruesink, Terry (2)
Yaszemski, Michael J. (2)
Casper, Michelle E. (1)
Currier, Bradford L. (1)
Giraldo, Catalina Vallejo (1)
Giuliani, Melissa (1)
Hefferan, Theresa E. (1)
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The effects of fixed electrical charge on chondrocyte behavior
Casper, Michelle E.
Hefferan, Theresa E.
Currier, Bradford L.
In this study, we have compared the effects of negative and positive fixed charge on chondrocyte behavior in vitro. Electrical charges have been incorporated into oligo(poly(ethylene glycol) fumarate) (OPF) using small charged monomers such as sodium methacrylate (SMA) and (2-(methacryloyloxy) ethyl)-trimethyl ammonium chloride (MAETAC) to produce negatively and positively charged hydrogels, respectively. The hydrogel physical and electrical properties were characterized through measuring and calculating the swelling ratio and zeta potential, respectively. Our results revealed that the properties of these OPF modified hydrogels varied according to the concentration of charged monomers. Zeta potential measurements demonstrated that the electrical property of the OPF hydrogel surfaces changed due to incorporation of SMA and MAETAC and that this change in electrical property was dose-dependent. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy was used to determine the hydrogel surface composition. To assess the effects of surface properties on chondrocyte behavior, primary chondrocytes isolated from rabbit ears were seeded as a monolayer on top of the hydrogels. We demonstrated that the cells remained viable over 7 days and began to proliferate while seeded on top of the hydrogels. Collagen type II staining was positive in all samples; however, the intensity of the stain was higher on negatively charged hydrogels. Similarly, GAG production was significantly higher on negatively charged hydrogels compared to neutral hydrogel. Reverse transcription polymerase chain reaction showed up-regulation of collagen type II and down-regulation of collagen type I on the negatively charged hydrogels. These findings indicate that charge plays an important role in establishing an appropriate environment for chondrocytes and hence in the engineering of cartilage. Thus, further investigation into charged hydrogels for cartilage tissue engineering is merited.
hydrogel; cartilage tissue engineering; OPF; scaffold
A Stimuli-Responsive Hydrogel for Doxorubicin Delivery
Giraldo, Catalina Vallejo
The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.
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