Anti-Inflamatory Coatings for Biomaterials

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DESCRIPTION (provided by the applicant): The prolonged inflammatory response to an implant is one of the primary causes for the failure to integrate into tissue. The two sources of inflammation common to almost all implants are the foreign body response and the relative movement of the implant with the surrounding tissue. Based on evidence in the literature and from our research team, the inflammatory response is mediated by the reactive oxygen species generated by macrophages, leukocytes, and the surrounding connective tissue. Based on our findings, it is evident that titanium dioxide and similar ceramics, even when present as surface coatings of polymeric biomaterials, have the ability to breakdown reactive oxygen species that have been identified as mediators of the inflammatory response. The goal of this Program is to develop applications for our catalytic antioxidant ceramic technology in the biomaterials and medical device industry. This Program, led by UCSD, consists of five projects with ten academic and industrial partners. Project 1 will investigate the basic mechanisms of action of metal oxides in the catalytic breakdown of reactive oxygen species. By understanding the fundamental reaction kinetics of the catalytic action of titanium dioxide, catalysts of greater efficiency may be discovered. Project 2 will fabricate and characterize materials for the other four projects. This project involves partners from Lawrence Livermore National Labs, Drexel Univ., and UCSD. Project 3 will test the in vivo inflammatory and foreign body response in two in vivo models; a standard rat model and the hamster window model. This project provides a core service to the other projects, but also investigates fundamental mechanisms of the inflammatory response to biomaterials. Project 4 will determine if the catalytic antioxidant ceramic technology is able to mitigate implant-tissue strain-induced inflammation. It will also investigate basic mechanisms of strain-induced inflammation. Project 5 is the interface with the medical device industry. Four Industrial Partners have been chosen to develop to apply the technology to four different biomaterial needs: Biosensor membranes for inplantable glucose sensors (GlySens) and biodegradable polymers for tissue engineering (Advanced Tissue Sciences) with reduced foreign body response; wound dressing material with anti-inflammatory properties (3M); and. dental materials with improved soft tissue integration (Nobel BioCare). By the first year, we will have elucidated the catalytic mechanisms of action of TiO,, established the ceramic coating technologies, characterized the inflammation response in the hamster model, and fabricated and tested dental coatings. Our overall objective is to provide the proof-of-principle to our industrial partners, which will encourage them to participate in more specific product development in the second phase (years 6-10) of the BRP.