Naoki Nishishita

Controlled Angiogenic Factor Release from Alginate Gels

Therapeutic angiogenesis by localized delivery of angiogenic factors is a promising approach to treat patients with cardiovascular disease and to engineer large tissues. Vascular endothelial growth factor (VEGF) is the most common and biologically active form of the VEGF family, which acts as a mitogen to endothelial cells and is capable of specific binding to heparin. However, when VEGF is administered via bolus injection, it can be widely distributed, and its concentration is likely to be within the effective window for only a short time period due to rapid degradation. Delivery of angiogenic factors, using controlled drug delivery strategies, offers great potential to promote angiogenesis at a specific site while reducing the unwanted side effects that may occur with systemic delivery. We now report on the sustained release of VEGF from alginate gels, modified with a heparin-binding peptide. Briefly, a small peptide with the sequence of G5K(βA)FAKLAARLYRKA, which is known to specifically interact with heparin, was chemically conjugated to alginate, and the peptide-modified alginate formed gels after mixing with heparin and VEGF. The release rate of VEGF from the gels slowed in vitro for over 45 days, compared with release from non-modified alginate gels. This result suggests potential applications of alginate gels in promoting angiogenesis for therapeutic purposes, as well as for tissue engineering.

Examination of bacterial toxin measurement using Quartz crystal microbalance method

When renal failure patients undergo the hemodialysis, the endtoxin (ET) that is the bacterial toxin that causes the symptom such as generation of heat is measured as one of the pollution markers. Presently, because the high performance filtration equipment develops, the amount of ET in dyalysate water and solution was achieved under the ET standard value set by Japanese Society for Dialysis Therapy etc. However, the ET measurement is obligated to the moon a couple of degrees at the dialysis center etc. the measurement is needed for 30 minutes or more since it use batch method and rely on the chemical reaction. In this study, we paid attention to the polyamino acid named epsiv-polylisine (epsiv-PL) that can select and adsorb ET and the mass measurement using quartz crystal microbalance method (QCM). We aim to the development of the real-time ET measuring system using these. If it is achieved, the amount of ET can be monitored while blood is dialyzed. Moreover, it seems that treatment that discontinues dialyzing can be taken when it exceeds the reference value.