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

Arizona State University, Scottsdale AZ

Investigators

Abstract

0238917 Panitch This 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.