Collaborative Research: Conformal Assemblies of Polyphosphazenes with Controlled Biofuncationality
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PART I: NON-TECHNICAL SUMMARYThis project focuses on engineering multifunctional biomaterials with advanced capabilities such as controlled protein adsorption and the ability to self-heal. Many current, clinical polymer coatings are susceptible to a build-up of proteins on the surface once in the body. While solutions have been proposed, it remains a challenge to combine the ability to repel proteins with other advanced capabilities such as self-healing and controllable drug release. This project focuses on the creation of coatings for devices such as coronary stents, catheters, or artificial implants, which are all in intimate contact with a large variety of biological milieu. Therefore, it is desirable for such coatings to (a) be easy to apply to a variety of biomedically relevant substrates in a controllable manner; and (b) be biocompatible and biodegradable with predictable, non-toxic degradation components. The layer-by-layer (LbL) technique is chosen as a powerful means to create conformal coatings of controlled thickness on virtually any surface from all aqueous assembly. This project will explore the ability of novel hybrid polymers, which are based on an inorganic backbone with structurally diverse organic pendant groups, to assemble via the LbL technique, undergo controlled degradation, and facilitate modulated release of bioactive molecules. The goal will be to achieve easy to manufacture biocompatible coatings that combine the desired properties. Advanced instrumental techniques will be used to understand the effects of coating chemistry on ability to self-heal, prevent protein adhesion, and load/release drugs along with the ability to control interactions with biological surroundings. Importantly, this project will create a fertile training ground for the participating graduate and undergraduate students which will be recruited via the Aggie Research Program. One PI is currently the academic advisor of the "Women in Materials Science" (WIMS) organization, which promotes the inclusion of female and minority students in science & engineering through active engagement in outreach activities both on and off campus. The other PI is actively involved in "Frontiers in Science and Medicine Day" for middle school students.PART II: TECHNICAL SUMMARYThe search for multifunctional biomaterials interfacing biological systems, such as artificial implants, including coronary stents and catheters, is one of the most critical and challenging areas of life sciences. Current polymer coatings in clinical use are based on traditional commodity polymers, are often deposited on solid surfaces via solution casting using organic solvents, lack desired chemical functionalities, and reliable control over loading and release of bioactives. This proposal aims to (a) explore the fundamental properties of layer-by-layer (LbL) assemblies based on novel polyphosphazene (PPz) polyelectrolytes with tailored bio-functionality, (b) probe structure-property relationships through a set of experiments addressing physico-chemical properties of the films, and relate them to protein adsorption and adhesion of smooth muscle and epithelial cells, and (c) explore the combination of self-healing and controlled drug release. This project will involve synthesizing novel PPz polyelectrolytes, which combine a unique mixture of properties (extreme chain flexibility, unprecedented structural diversity, multi-functionality, and controlled hydrolytic degradability). Electrostatic interactions will be used to form well defined polyelectrolyte multilayers, whose thickness and growth patterns will be characterized with ellipsometry. Inclusion of bioactive molecules will be studied through direct self-assembly of PPzs with small charged molecules, while amount loaded and released of small molecules will be studied using LC-MS. Moreover, the interaction of such coatings with human endothelial and smooth muscle cells, adsorption of proteins, (HSA, fibrinogen) and biocompatibility will be assessed. These findings will enable rational design of biocompatible coatings for self-healing and drug-loading for applications such as coronary stents, catheters, or artificial implants.This award reflects NSF''s statutory mission and has been deemed worthy of support through evaluation using the Foundation''s intellectual merit and broader impacts review criteria.
