Targeting and altering in vivo macrophage responses with modified polymer properties

Abstract

Event Abstract Back to Event Targeting and altering in vivo macrophage responses with modified polymer properties Hannah C. Bygd1, Kiva D. Forsmark2 and Kaitlin M. Bratlie1, 2 1 Iowa State University, Materials Science & Engineering, United States 2 Iowa State University, Chemical & Biological Engineering, United States Introduction: Two pathways for activating MΦs exist. One of these routes is termed the classically activated M1 pathway and is achieved through exposure to lipopolysaccharide (LPS). M1 MΦs are known as pro-inflammatory cells. The other pathway is reached through interleukin-4 (IL-4) and is known as the alternatively activated M2 pathway. M2 MΦ produce pro-angiogenic factors. Here, we successfully use in vivo imaging and histological analysis to identify the MΦ response and activation. We demonstrate the ability to induce various MΦ phenotypes with a change in material functionality as well as identify certain materials parameters that seem to correlate with each phenotype. This suggests the potential to develop materials for specific applications and predict the outcome of MΦ activation in response to new surface chemistries. Experimental Methods: The poly(N-isopropylacrylamide) (pNIPAm) (~600nm) particles were synthesized using established methods and modified through conjugation with surface modifiers through carbodiimide chemistry. MΦs were polarized to the M1 and M2 phenotypes and internalization of functionalized pNIPAm particles were measured. These materials were also subcutaneously injected in SKH1-E mice. Arginase:iNOS profiles have been consistently used as a measure of MΦ phenotype. Arginine activity was measured indirectly through a urea assay in which the lysate was activated, exposed to arginine, and conversion to urea was quantified. Nitrites were measured through a Griess reagent assay to indirectly determine the levels of inducible nitric oxide synthase (iNOS). Material properties of the modified particles including water contact angle, melting temperature, and zeta-potential were also measured. Results: SKH1-E mice were injected with the polymer particles and imaged for cathepsin activity (Figure 1). A range in cathepsin activity was observed for the different surface modifiers. The tissue sections from the mice in Figure 1 were excised and homogenized. The arginase:iNOS displayed a spectrum between the M1 and M2 phenotypes for different surface modifiers as shown in Figure 2. Discussion: Distinct material parameters influence MΦ phenotypes. For example, increasing the hydrogen bonding of polymeric particles can polarize MΦs towards the M1 phenotype. The induction of multiple MΦ phenotypes confirms the ability to control MΦ activation in vivo and suggests the importance of chemical properties in the biocompatibility of materials. The results obtained suggest that changing properties can result in opposite MΦ phenotypes. Conclusion: With this work, useful insight was gained about in vivo MΦ response to various material functionalities. Overall, this in vivo study was successful at drawing conclusions about the biomaterial parameters that will allow for tuning MΦ polarization responses to biomaterials and targeting MΦs. National Science Foundation; Roy J. Carver Charitable Trust Keywords: in vivo, cell phenotype, Cell response, Cell modulation Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in immune response Citation: Bygd HC, Forsmark KD and Bratlie KM (2016). Targeting and altering in vivo macrophage responses with modified polymer properties. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02096 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hannah C Bygd Kiva D Forsmark Kaitlin M Bratlie Google Hannah C Bygd Kiva D Forsmark Kaitlin M Bratlie Google Scholar Hannah C Bygd Kiva D Forsmark Kaitlin M Bratlie PubMed Hannah C Bygd Kiva D Forsmark Kaitlin M Bratlie Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.