- Assistant Professor
- Mike and Denise Mack Faculty Fellow
- Materials Science and Engineering
- Chemical & Biological Engineering
Main Office2220BK Hoover
Ames, IA 50011
Ph.D. Physical Chemistry, University of California, Berkeley, 2007 B.S. Chemistry, University of Minnesota, Institute of Technology, 2003
Bratlie research group: Our long-term goal is to determine how polymers interact with biological tissues so that new and innovative strategies can be developed for improved outcomes in various maladies that affect the human condition, such as type 1 diabetes, cancer, and wound healing. We attack these problems through complementary techniques such as whole animal imaging, second-order nonlinear optical imaging, histology, and in vitro analysis of cellular responses to polymers.
1. Reprogramming tumor associated macrophages: Engineering polymer surface properties to discriminately deliver drugs
Macrophages can be polarized to produce pro-angiogenic and pro-inflammatory molecules. Some tumors have pro-angiogenic macrophages associated with them. These tumors typically have very poor prognoses, as these pro-angiogenic macrophages will secrete factors that promote neovascularization, thus providing a nutrient supply for the tumor. Macrophages can be reprogrammed through delivering interleukin-12. Our approach to this project, guided by strong results obtained at Iowa State, is to use polymers, which will eventually be used to deliver anti-cancer drugs, to reprogram the macrophages such that they become pro-inflammatory. The advantage of these pro-inflammatory macrophages is that they will produce molecules such as tumor necrosis factor-α, which are toxic to malignant cells
2. Developing pro-angiogenic polymers to increase the survival of encapsulated islets for type 1 diabetes therapy
With the previous research aim, we were interested in using drug delivery devices to cause macrophages to be pro-inflammatory. This research project takes the opposite stance in which we are interested in producing pro-angiogenic macrophages to increase the longevity of encapsulated insulin-producing cells. Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic islets are destroyed by the immune system. Transplanting islets into a patient can treat this disease; however, that requires immunosuppressive drugs, which is not a desirable treatment. Through encapsulating the islets in a polymer, the immune response to the cells can be avoided. The problem with this approach generally lies in the polymer evoking a fibrotic response and choking off the nutrient supply to the islets. We are interested in developing polymers that cause macrophages to be pro-angiogenic so that blood vessels would form around this device and would increase its longevity. This approach can be applied to other tissue engineering applications, such as wound healing, cardiac tissue engineering, and bone regeneration.
3. In vivo probes for assessing the foreign body response
The previous two research areas exploit whole animal imaging to understand host responses to biomaterials. We are also interested in increasing and improving the imaging methods available to us. Real-time imaging is an extremely powerful tool that allows us to obtain a picture regarding what is happening in our animal models. Currently, we use luminol and a cathepsin probe to monitor responses to implanted biomaterials. We are working to expand this to include nonlinear optical imaging, which is deftly able to explore collagen formation and orientation. We are using this technique to explore wound-healing polymers and get a sense of how collagen formation occurs in response to different hydrogels. We are also working to develop a multiplex library of fluorescent probes to examine the matrix metalloproteinase response to biomaterials. Matrix metalloproteinases are enzymes that degrade the extracellular matrix. This process is triggered when biomaterials are implanted and the exact profile of these different enzymes is largely unknown.
Work Experience: 2011-present, Assistant Professor, Department of Materials Science and Engineering/Department of Chemical and Biological Engineering, Iowa State University 2008-2011, National Institutes of Health (NIH) Postdoctoral Fellow, Massachusetts Institute of Technology
- H.C. Bygd, D. Akilbekova, A. Munoz, K.D. Forsmark, K.M. Bratlie Poly-L-arginine based materials as instructive substrates for fibroblast syntheses of collagen 2015, Biomaterials 63, 47
- H. Tran, K.M. Bratlie Inhibition of MMP-13 with modified polymer particles (invited Gabor A. Somorjai Festschrift) 2015, Surface Science available online
- H.C. Bygd, K.D. Forsmark, K.M. Bratlie Altering in vivo macrophage responses with modified polymer properties, 2015, Biomaterials 56, 187
- D. Akilbebekova, K.M. Bratlie Quantitive Characterizatiion of Collagen in the Fibrotic Capsule Surrounding Implanted Polymeric Microparticles through Second Harmonic Generation Imaging 2015, PLoS ONE 10, e0130386
- H.C. Bygd, K.D. Forsmark, K.M. Bratlie The significance of macrophage phenotype in cancer and biomaterials, 2015, Clinical and Translational Medicine, 3, 62.
- D. Akilbekova, R. Philiph, A. Graham, K.M. Bratlie Macrophage reprogramming: Influence of latex beads with various functional groups on macrophage phenotype and phagocytic uptake in vitro, 2015, Journal of Biomedical Materials Research Part A 103A, 262
- D. Wang, N. Phan, C. Isely, L. Bruene, K.M. Bratlie Effect of surface modification and macrophage phenotype on particle internalization, 2014, Biomacromolecules, 15, 4102
- K. M. Bratlie, R. L. York, M. A. Invernale, R. Langer, D. G. Anderson. Materials for diabetes therapeutics, 2012, Advanced Healthcare Materials 1, 267.
- K.M. Bratlie, T.T. Dang, S. Lyle, M. Nahrendorf, R. Weissleder, R. Langer, D.G. Anderson. "Rapid Biocompatibility Analysis of Materials via In Vivo Fluorescence Imaging of Mouse Models," PLoS ONE 2010, 5, e10032.