CAREER: Self-Protecting Artificial Implants and Invigorating the STEM Education Pipeline with Biomaterials

Clemson University, Clemson SC

Investigators

Abstract

Non-technical: This CAREER award made by the Biomaterials program in the Division of Materials Research to Clemson University will study the development of artificial implant materials with modified surfaces. These coatings are expected to resist deterioration and failure of implant materials by actively decreasing the circulating oxygen-induced material damage. The human immune system reacts to an artificial implant, such as a replacement hip or knee joint, by attacking it and degrading it chemically. Eventually, this implant could fail and then need to be repaired or replaced, and involves surgeries that could be too risky for many elderly and infirm patients. The immune system could still attack an artificial implant even under rigorously sterile conditions and even with "inert" materials, such as stainless steel. The studies carried out with this NSF CAREER award would lead to development of artificial implants with novel coatings that resist failure by actively preventing their chemical degradation. The proposed research would benefit society significantly by: (1) extending the functional lifetimes of artificial implants; (2) reducing morbidity and mortality risks, particularly among elderly and infirm patients; and (3) decreasing pain and inflammation that occur after implantation. This investigator plans to integrate the research activities of college students into this research. Additionally, K-12 teachers will be offered a summer course designed to help them incorporate biomaterial topics into their K-12 science classes. This award will address the current shortfall in science, technology, engineering and mathematics degrees by fostering interest in and successful completion of these degrees by underserved and underrepresented students. This award is co-funded by the Physiology, Mechanisms & Biomechanics program in the Division of Integrative Organismal Systems, and Emerging Frontiers program, both in the Directorate for Biological Sciences. Technical: Human implantation of an artificial material into a human triggers the foreign body reaction (FBR), which leads to adhering of macrophages to the artificial implant materials (AIM) and damaging them via the release of reactive oxygen species (ROS). Eventually, ROS-induced AIM damage could cause the implant to fail, necessitating additional surgical procedures that could result in high morbidity and mortality risks. These hazards are currently unavoidable, as the FBR occurs under even rigorously sterile conditions and the accompanying ROS damages in chemically-inert implant materials such as stainless steel and fluoropolymer plastics. This CAREER award would enable the development of biocompatible AIMs that resist deterioration and failure of implants by actively decreasing ROS-induced material damage. The first aim of the project is to covalently link self-regenerating catalyst coatings based on N-heterocyclic carbine-ruthenium complexes to artificial implant materials such as polymers [poly(methyl methacrylate), polyethylene, polypropylene, etc.] and inorganic materials (hydroxyapatite, titanium, titania, stainless steel, etc.). In addition to the preparation of large number of substrates with catalyst coatings, linker systems and surface loadings, these modified implant materials will be tested against different cell cultures/media to establish the ability of these immobilized catalysts to reduce reactive oxygen before and after exposure to cells for up to two weeks. The second aim of this award is: a) to study damage to implant materials under simulated FBR conditions in vitro; and b) to visualize and quantify the production of ROS and inflammatory cytokines of macrophages reacting to catalytically active substrates. Additionally, this CAREER award would also contribute in reducing the STEM degree shortfall facing the U.S., particularly among underserved and underrepresented minority students, by integrating technical college students into biomaterials research, and teaching biomaterial concepts and topics to K-12 science teachers.