EducationPh.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.
- Reprogramming tumor associated macrophages: Engineering polymer surface properties to discriminately deliver drugs
Macrophages exist on a continuum of phenotypes that span from pro-inflammatory to pro-wound healing. The number of pro-wound healing macrophages found in the tumor microenvironment is correlated with poor prognosis in a variety of cancers. Furthermore, pro-inflammatory macrophages secrete tumoricidal molecules. The goal of this work is to develop an understanding of how macrophages respond to polymers such that these materials can be used to reprogram the macrophages. One of the tools that we use to improve rational design is through developing mathematical models using quantitative structure-activity relationships, which has been applied to other applications in biomaterials such as drug delivery. Our ultimate goal with this work is to develop a drug delivery system that would deliver a chemotherapeutic and would polarize tumor-associated macrophages towards a pro-inflammatory phenotype such that the macrophages and chemotherapeutic would act synergistically to kill the malignant cells.
- 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.
- Imaging the foreign body response
We use second harmonic generation to assess the amount of collagen produced, its type, and its fiber orientation in response to the polymers that we synthesize. One of the major advantages of using second-order nonlinear optical techniques, such as second harmonic generation, is that isotropic molecules from the cell culture media do not contribute to the signal. We are also able to carry out these measurements without using a molecular probe. In addition, we develop in vivo
probes for assessing the foreign body response. In vivo animal imaging is a powerful method for extracting real-time data. I have contributed to this area by developing methods for monitoring biocompatibility of multiple materials simultaneously. Fluorescence imaging will never replace traditional histological analysis, but it can provide complementary data to better understand material-host interactions. One of the fluorescent probes used is a polymer scaffold of poly-L-lysine that is pegylated to improve circulation time. The Cy5.5 fluorophores are grafted onto a polymer backbone to allow imaging in the optical window. These fluorophores were quenched when the polymer was in the intact state. Upon cleavage of the poly-L-lysine by cathepsin, the fluorophores de-quenched, generating a fluorescent signal. The fluorescent signal was shown to correlate well with macrophage and neutrophil recruitment, as quantified by a board-certified pathologist, and was used to evaluate innate immune cell recruitment to implanted biomaterials as a function of time.
Brief BiographyWork 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
- A. Boddupalli,^ L. Zhu,^ K.M. Bratlie Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes 2016, Advanced Healthcare Materials, 5, 2575. ^These authors contributed equally to this manuscript.
- A. Dunn-Sale, K.M. Bratlie Identifying Factors of Microparticles Modified with Arginine Derivatives That Induce Phenotypic Shifts in Macrophages 2016, ACS Biomaterials Science and Engineering, 2, 946.
- H.C. Bygd, K.M. Bratlie The effect of chemically modified alginates on macrophage phenotype and biomolecule transport 2016, Journal of Biomedical Materials Research Part A, 104, 1707.
- A. Boddupalli, K.M. Bratlie Multimodal imaging of harmonophores and application of high content imaging for early cancer detection (invited review) 2015, Materials Discovery, 1, 10.
- H. Tran, K.M. Bratlie Inhibition of MMP-13 with modified polymer particles (invited Gabor A. Somorjai Festschrift) 2015, Surface Science 648, 371.
- D. Akilbekova, K.M. Bratlie Quantitative Characterization of Collagen in the Fibrotic Capsule Surrounding Implanted Polymeric Microparticles through Second Harmonic Generation Imaging 2015, PLoS ONE 10, e0130386
- H.C. Bygd, D. Akilbekova, A. Munoz, K.D. Forsmark, K.M. Bratlie Poly-l-arginine based materials as instructive substrates for fibroblast synthesis of collagen 2015, Biomaterials 63, 47
- H.C. Bygd, K.D. Forsmark, K.M. Bratlie Altering in vivo macrophage responses with modified polymer properties, 2015, Biomaterials 56, 187.
- D. Wang, K.M. Bratlie On the influence of polymer chemistry on cytokine secretion from polarized macrophages, 2015, ACS Biomaterials Science & Engineering 1, 166.
- 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.