Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.

Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites. Human innate immune macrophages were verified as essential to biomaterial rejection in this model and were capable of cross-talk with mouse fibroblasts for collagen matrix deposition. Cytokine and cytokine receptor array analysis confirmed core signaling in the fibrotic cascade. Foreign body giant cell formation, often unobserved in mice, was also prominent. Last, high-resolution microscopy coupled with multiplexed antibody capture digital profiling analysis supplied spatial resolution of rejection responses. This model enables the study of human immune cell-mediated fibrosis and interactions with implanted biomaterials and devices

Microfabrication and electrical characterization of lead-free sodium potassium niobate thin film ribbons on conformal substrates

Thesis: S.M., Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2019Cataloged from PDF version of thesis.Includes bibliographical references (pages 40-41).There have been recent concerns regarding the use, recycling, and disposal of the predominantly used leaded piezoelectric ceramic- Lead Zirconate Titanate (PZT). The European Union has initiated restricting the use of lead in commercial products, with countries such as China and Japan. These regulations provide further motivation for the development of an alternative to leaded piezoelectric materials. The aim of this thesis is to characterize the more recently researched lead-free piezoelectric alternative, Sodium Potassium Niobate (KNN). Thin films of KNN ribbons with gold interconnects are microfabricated on various conformal substrates such as Kapton, Ecoflex, Polydimethylsiloxane (PDMS), and Silbione/fabric and characterized electrically using the Keithley Semiconductor Parameter Analyzer. In this initial experimental evaluation, it was found that at the frequency of 100 KHz, the dielectric constant of the KNN on PDMS is the highest at 427 followed by the Kapton at 410. The Ecoflex and Silbione/fabric both have a dielectric of about 387. In the literature, the dielectric constant of KNN is reported to fall between 185 and 598 based on the substrate it is on, and our values are well within this reported range. The results from the other electrical characterization tests indicate that the KNN behaves similarly on the different tested substrates as the capacitance, polarization curve, and leakage current of all the devices are in the same range and are close as the ribbons are swept from -40 V to 40 V.by Atieh Sadraei.S.M.S.M. Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Science

Talking about Food: Improving Communication Between Ghanaian Women and Medical Practitioners

Worcester has the highest infant mortality rate in Massachusetts, and it is most prevalent in the Ghanaian community. In collaboration with Nhyira Ba, a Ghanaian led organization, we addressed communication barriers between medical practitioners and Ghanaian women on issues related to nutrition, food preparation, and the role of food in Ghanaian culture, by producing educational videos targeted at medical practitioners. With this effort we hope to create greater understanding between practitioners and their Ghanaian patients

Theranostics of Glioblastoma Multiforme: In Vitro Characterization of Targeted Nanoemulsions and Creation of a 3D Statistical Heatmap to Visualize Nanoemulsion Uptake

Glioblastoma Multiforme (GBM) continues to be a leading form of malignant brain cancer. GBM presents a high variability patient to patient. This provides a need for a theranostic system capable of both delivering therapeutic and in real-time visually observe results. Current methods involve months between treatment application and available results. Based on Nemucore Medical Innovation’s drug delivery vehicles, nanoemulsions (NE) containing chemotherapeutics are being utilized to target cancer cells and reduce systemic toxicity. Through the automation of required statistical analysis and creation of a wire-frame rat brain model with 174 defined brain regions a software capable of providing ‘real-time’ pharmacodynamics analysis of Gd3+ annotated, receptor-targeted NE is one step closer

Reduction of measurement noise in a continuous glucose monitor by coating the sensor with a zwitterionic polymer

© 2018, Nature Publishing Group. All rights reserved. Continuous glucose monitors (CGMs), used by patients with diabetes mellitus, can autonomously track fluctuations in blood glucose over time. However, the signal produced by CGMs during the initial recording period following sensor implantation contains substantial noise, requiring frequent recalibration via finger-prick tests. Here, we show that coating the sensor with a zwitterionic polymer, found via a combinatorial chemistry approach, significantly reduces signal noise and improves CGM performance. We evaluated the polymer-coated sensors in mice as well as in healthy and diabetic non-human primates, and show that the sensors accurately record glucose levels without the need for recalibration. We also show that the coated sensors significantly abrogated immune responses, as indicated by histology, fluorescent whole-body imaging of inflammation-associated protease activity and gene expression of inflammation markers. The polymer coating may allow CGMs to become standalone measuring devices.This work was supported by the Leona M. and Harry B. Helmsley Charitable Trust Foundation (2015PG-T1D063), Juvenile Diabetes Research Foundation (JDRF) (Grant 17-2007-1063), and National Institutes of Health (Grants EB000244, EB000351, DE013023 and CA151884), and through a generous gift from the Tayebati Family Foundation. J.C.D was supported by JDRF postdoctoral fellowship (Grant 3-PDF-2015-91-A-N). J.O. is supported by the National Institutes of Health (NIH/NIDDK) R01DK091526 and the Chicago Diabetes Project. X.X. was supported by the 100 Talents Program of Sun Yat-Sen University (76120-18821104) and 1000 Talents Youth Program of China and would like to acknowledge financial support from the National Natural Science Foundation of China (Grant No.51705543, 61771498 and 31530023) and Science and Technology Program of Guangzhou, China (Grant No. 20180310097). And, of extreme importance, the authors thank the Histology and Whole Animal Imaging cores for use of resources (Swanson Biotechnology Center, David H. Koch Institute for Integrative Cancer Research at MIT)

Colony Stimulating Factor-1 Receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates

Host recognition and immune-mediated foreign body response (FBR) to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knock out and CXCL13 neutralization. Interestingly, Colony Stimulating Factor-1 Receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer, and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, ROS production, and phagocytosis. Our results indicate targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression