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

0238917 Panitch这项工作的重点是合成和表征的仿生，自组装水凝胶，可用于生物活性化合物的输送。这些水凝胶在几个方面是独特的：它们是具有软膏稠度的物理凝胶，可以原位聚合或铺展到区域上;药物从凝胶中的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;并且凝胶的溶解可以基于组分彼此的亲和力来控制。假设通过结合肽修饰的聚（乙二醇）星星聚合物（PEG星星）和硫酸化多糖形成的物理凝胶可以被定制以控制凝胶的溶解和生物活性组分的释放。进一步假设这些凝胶将在生理相关的时间尺度上释放生物活性组分。为了验证这些假设，将用4臂和8臂PEG星和肝素、硫酸软骨素或硫酸葡聚糖制备凝胶。凝胶将补充四种不同的多糖结合肽，肽的释放将进行研究。最后，将针对血管舒张的情况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。这些释放系统可以原位聚合，是柔软和柔韧的，并且可以用于需要具有控释特性的软膏样材料的临床情况。第一个目标应用是在体外隐静脉模型中促进血管舒张的凝胶。所提出的工作适合于从物理凝胶和共价凝胶两者的受控释放的未来工作;基于生物的和合成的分子可以被定制以经由类似的方案释放。此外，支架可用作人工细胞外基质，其能够螯合因子、释放因子并维持细胞生长和存活。教育部分包括在亚利桑那州立大学的课程开发以及推广到斯科茨代尔社区学院。 开设分子、细胞与组织工程概论课程。这门课将服务于几个目的：研究生的机会，成为参与课程开发和教学，社区学院的学生接触生物工程和实验室的机会，本科生从斯科茨代尔社区学院的创建。

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.