CAREER: Biomimetic Self-Assembling Hydrogels for Delivery for Bioactive Molecules

0238917这项工作专注于仿生、自组装水凝胶的合成和表征，这些水凝胶可用于输送生物活性化合物。这些水凝胶在几个方面将是独一无二的：它们是具有软膏稠度的物理凝胶，可以在现场聚合或涂抹在一个区域上；凝胶中的药物释放取决于药物对凝胶的亲和力；药物对凝胶的亲和力可以定制；凝胶的溶解可以根据成分之间的亲和力进行控制。假设由多肽修饰的聚乙二醇星形聚合物(PEGSTAR)和硫酸多糖形成的物理凝胶可以被定制来控制凝胶的溶解和生物活性成分的释放。进一步假设，这些凝胶将在生理上相关的时间尺度上释放生物活性成分。为了验证这些假设，我们将用4臂和8臂的聚乙二醇星和肝素、硫酸软骨素或硫酸葡聚糖制成凝胶。凝胶将被四种不同的多糖结合肽补充，并将研究这些肽的释放。最后，在血管松弛的情况下，将测试凝胶的生物活性和生理应用。该项目的总体目标是开发一类新的水凝胶释放系统。这些释放系统可在原位聚合，柔软而柔韧，可用于临床需要具有控释特性的软膏状材料。第一个目标应用是一种在体外大隐静脉模型中促进血管扩张的凝胶。这项拟议的工作有助于未来从物理凝胶和共价凝胶中进行控制释放的工作；基于生物的和合成的分子可以通过类似的方案进行定制以释放。此外，支架还可以作为人工细胞外基质，具有隔离因子、释放因子、维持细胞生长和存活的能力。教育部分包括亚利桑那州立大学的课程开发以及与斯科茨代尔社区学院的联系。将开设分子、细胞和组织工程概论课程。本课程将服务于几个目的：为研究生提供参与课程开发和教学的机会，让社区学院的学生接触生物工程，并为斯科茨代尔社区学院的本科生创造实验室机会。

0238917PanitchThis work focuses on the synthesis and characterization of biomimetic, self-assembling hydrogels that are useful for delivery of bioactive compounds. These hydrogels will be unique in several respects: they are physical gels with the consistency of ointment that can be polymerized in situ or spread onto an area; drug release from the gels is dependant on the affinity of the drug for the gel; the affinity of the drug for the gel can be tailored; and the dissolution of the gel can be controlled based on the affinity of the constituents for one another. It is hypothesized that physical gels formed by combining peptide-modified poly(ethylene glycol) star polymers (PEG stars) and sulfated polysaccharides can be tailored to control both dissolution of the gel and release of bioactive components. It is further hypothesized that these gels will release bioactive components on a physiologically-relevant time scale. To verify these hypotheses, gels will be made with 4-arm and 8-arm PEG stars and heparin, chondroitin sulfate or dextran sulfate. The gels will be complemented with four distinct polysaccharide-binding peptides, and the release of the peptides will be studied. Finally, the bioactivity and physiological application of the gel will be tested for the case of vasorelaxation. The overall goal of the project is to develop a new class of hydrogel release systems. These release systems can be polymerized in situ, are soft and pliable and can be used in clinical situations where ointment-like materials with controlled release characteristics are necessary. The first target application is a gel that promotes vasodilation in an in vitro saphenous vein model. The proposed work lends itself to future work in controlled release from both physical gels and covalent gels; biologically- based and synthetic molecules can be tailored to release via similar schemes. In addition, the scaffolds can be used as artificial extracellular matrices, which are capable of sequestering factors, releasing factors and sustaining cell growth and survival. The educational component consists of curriculum development at ASU as well as outreach to Scottsdale Community College. A survey course of Molecular, Cellular and Tissue Engineering will be developed. This class will serve several purposes: the opportunity for graduate students to become involved in course development and in teaching, the exposure of community college students to bioengineering and the creation of laboratory opportunities for undergraduate students from Scottsdale Community College.