Carrageenan-based hydrogels for the controlled delivery of PDGF-BB in bone tissue engineering applications

One of the major drawbacks found in most bone tissue engineering approaches developed so far consists in the lack of strategies to promote vascularisation. Some studies have addressed different issues that may enhance vascularisation in tissue engineered constructs, most of them involving the use of growth factors (GFs) that are involved in the restitution of the vascularity in a damaged zone. The use of sustained delivery systems might also play an important role in the re-establishment of angiogenesis. In this study, !-carrageenan, a naturally occurring polymer, was used to develop hydrogel beads with the ability to incorporate GFs with the purpose of establishing an effective angiogenesis mechanism. Some processing parameters were studied and their influence on the final bead properties was evaluated. Platelet derived growth factor (PDGF-BB) was selected as the angiogenic factor to incorporate in the developed beads, and the results demonstrate the achievement of an efficient encapsulation and controlled release profile matching those usually required for the development of a fully functional vascular network. In general, the obtained results demonstrate the potential of these systems for bone tissue engineering applications.This work was supported by the European NoE EXPERTISSUES (NMP3-CT-2004-500283), the European STREP HIPPOCRATES (NMP3-CT-2003-505758), and by the Portuguese Foundation for Science and Technology (FCT) through the project PTDC/FIS/68517/2006 and through the V. Espirito Santo's Ph.D. grant (SFRH/BD/39486/2007)

The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells

<p>Abstract</p> <p>Background</p> <p>Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs.</p> <p>Methods</p> <p>Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB) and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated.</p> <p>Results</p> <p>We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity.</p> <p>Conclusion</p> <p>Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis.</p