Research Project
7611156
DESCRIPTION (provided by applicant): Current focus in improving acceptance of implants is to engineer materials that proactively control the interaction of the material surface with the biological milieu. Such control could ultimately lead to implants with long-term operational functionality due to the absence of the foreign body response. To successfully develop such a material, two strategies have been pursued: first, prevention of protein adhesion by developing nonadhesive coatings, and, second, enhanced implant/cell-interaction by immobilizing cell-specific ligands onto the antifouling coating. A further approach is focused on a class of cell-adhesion proteins found in the extracellular matrix containing the three amino acid sequence ArgGlyAsp (RGD) which binds to particular cell surface receptors (e.g. integrins). The focus of this Phase I research is to study a novel concept for improving the biocompatibility of any long-term implant by utilizing aptamers to provide a greatly improved communication between implant and interstitial fluid (ISF). The premise of the our novel technology will be to provide a multiplicity and redundancy of proactive interactions at the interface between implant and extracellular matrix (ECM) tissue for effective implant "camouflaging", in order to minimize acute inflammatory reaction, accelerate tissue reconstruction, and mitigate fibrotic capsule formation. To accomplish this task, we will identify aptamers, short sequences of oligonucleic acid selected from random libraries that bind to a variety of target molecules of the Extracellular Matrix (ECM). In Phase I, we will perform a proof-of-concept study by selecting aptamers specific to four prominent proteins found in the ECM, followed by immobilization of the identified aptamer ligands to the surface of a model implant (the BioTex glucose sensor already under development). We will then study the host-response of the aptamer- coated implant in a small animal model over several weeks. BioTex researchers are confident that this novel holistic approach, if successful, will be applicable to a wide number of implants to improve and extend their in vivo functionality. PUBLIC HEALTH RELEVANCE There is an urgent need for improved biocompatibility of long-term implants for applications such as glucose-monitoring in diabetes, cardiovascular stents, assistive and orthopedic devices, as well as therapeutic drug-delivery. What is common to all these biomedical implant applications is the need for a stable, proactive implant interface which causes the tissue matrix to be remodeled to mitigate the foreign body response. This project focuses on development of a chemistry that could be applied for a large number of implants and implant types in order enhance their functionality or prolong their survival in the body. This will be accomplished through the identification and utilization of a novel aptamers - high-affinity, highly selective nucleic acid ligands selected from large random libraries - coated to the external bioimplant surface which will provide multiple and redundant attachment points between bioimplant and Extracellular Matrix (ECM) of host tissue. The market for such a technology is hard to estimate due to the diverse number of implant applications, but without any doubt amounts to several billion dollars.
