In Vivo Imaging Methods for Assessing Foreign Body Responses to Polymer Systems

ChEMS Seminar

Featuring Kaitlin Bratlie, Ph.D.

Koch Institute of Integrated Cancer Research

Massachusetts Institute of Technology



Abstract:

The foreign body reaction has proven to be a hindrance to the functionality of implanted biomedical devices. The ability to direct this reaction, inflammation, and wound healing via the material-dependent control of key cellular components, macrophages and foreign body giant cells, is vital to the development of future biomedical devices. This cascade of events is determined by the surface chemistry of the implanted biomaterial. It has been demonstrated that material surface chemistry influences macrophage adhesion and fusion ultimately directing the cytokines/chemokines/MMPs/TIMPs released from biomaterial-adherent macrophages/foreign body giant cells.(1)

We are particularly interested in developing materials for reducing host-responses for polymer encapsulated insulin producing β-cells, which has potential as a type I diabetes therapeutic. Encapsulating β-cells in polymers to evade host-responses was first proposed by Lim & Sun(2) using alginate, a natural polymer derived from seaweed. These polymers are often coated with a poly-cation to improve perm-selectivity, which aids in reducing the host-response. Our approach has been to develop libraries of polymers for encapsulating β-cells and for coating the polymeric particles. We have also developed anti-inflammatory controlled release systems to further mitigate the foreign body response.

In assessing biocompatibility, our goal is to develop in vivo fluorescence imaging for assessing the host-response to libraries of implanted biomaterials to determine which chemical functionalities mitigate the foreign body response. We have developed two methods for imaging foreign body responses: cathepsin activity imaging and reactive oxide species imaging. Through these imaging platforms, we are able to assess early time-point responses to implanted materials. We have examined two libraries: one based on alginate for encapsulating β-cells and another for coating the polymer. Controlled release of anti-inflammatory drugs has also been examined. Histological analysis of these implanted materials complements early time point imaging in assessing host responses.

(1) Anderson, J. M.; Rodriguez, A.; Chang, D. T. Seminars in immunology. 2008, 20, 86-100.

(2) Lim, F.; Sun, A. M. Science (New York, NY). 1980, 210, 908.

About the Speaker:

Kaitlin Bratlie, Ph.D., is currently a post-doctoral fellow in the laboratory of Professor Robert Langer at MIT. Her current research involves developing techniques for characterizing the biocompatibility of materials in vivo as potential therapeutics for type I diabetes. She received her bachelors at the University of Minnesota in 2003. She completed her Ph.D. in chemistry at the University of California, Berkeley under the supervision of Professor Gabor Somorjai. Her Ph.D. research concerned examining the effect of nanoparticle shapes on catalytic reactions. Kaitlin has received numerous awards including a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health for her postdoctoral research.