scholarly journals Immune-informed mucin hydrogels evade fibrotic foreign body response in vivo

2019 ◽  
Author(s):  
Hongji Yan ◽  
Cédric Seignez ◽  
Morgan Hjorth ◽  
Benjamin Winkeljann ◽  
Oliver Lieleg ◽  
...  
Keyword(s):  
Foreign Body ◽  
Alder Reaction ◽  
Foreign Body Response ◽  
Inverse Electron Demand ◽  
Diels Alder Reaction ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Mucus Gel ◽  
Body Response

AbstractThe immune-mediated foreign body response to biomaterial implants can trigger the formation of insulating fibrotic capsules that can compromise implant function. To address this challenge, we leverage the intrinsic bioactivity of the mucin biopolymer, a heavily glycosylated protein that forms the protective mucus gel covering mucosal epithelia. By using a bioorthogonal inverse electron demand Diels-Alder reaction, we crosslink mucins into implantable hydrogels. We show that mucin hydrogels (Muc-gels) modulate the immune response driving biomaterial-induced fibrosis. Muc-gels did not elicit fibrosis 21 days after implantation in the peritoneal cavity of C57Bl/6 mice, whereas medical-grade alginate hydrogels (Alg-gels) were covered by fibrous tissues. Further, Muc-gels dampened the recruitment of innate and adaptive immune cells to the gel and triggered a pattern of very mild activation marked by a noticeably low expression of the fibrosis-stimulating TGF-β1 cytokine. With this advance in mucin materials, we provide an essential tool to better understand mucin bioactivities and to initiate the development of new mucin-based and mucin-inspired ‘immune-informed’ materials for implantable devices subject to fibrotic encapsulation.

Temporal Control of Efficient In Vivo Bioconjugation Using a Genetically Encoded Tetrazine-Mediated Inverse-Electron-Demand Diels–Alder Reaction

2020 ◽  
Vol 31 (10) ◽  
pp. 2456-2464
Author(s):  
Byungseop Yang ◽  
Kiyoon Kwon ◽  
Subhashis Jana ◽  
Seoungkyun Kim ◽  
Savanna Avila-Crump ◽  
...  
Keyword(s):  
Alder Reaction ◽  
Diels Alder ◽  
Temporal Control ◽  
Inverse Electron Demand ◽  
Diels Alder Reaction ◽  
Electron Demand

In vivo modulation of foreign body response on polyurethane by surface entrapment technique

2010 ◽  
Vol 95A (2) ◽  
pp. 413-423 ◽  
Author(s):  
Anand P. Khandwekar ◽  
Deepak P. Patil ◽  
Anand A. Hardikar ◽  
Yogesh S. Shouche ◽  
Mukesh Doble
Keyword(s):  
Foreign Body ◽  
Foreign Body Response ◽  
Body Response

scholarly journals Harnessing64Cu/67Cu for a theranostic approach to pretargeted radioimmunotherapy

2020 ◽  
Vol 117 (45) ◽  
pp. 28316-28327
Author(s):  
Outi Keinänen ◽  
Kimberly Fung ◽  
James M. Brennan ◽  
Nicholas Zia ◽  
Matt Harris ◽  
...  
Keyword(s):  
Therapeutic Response ◽  
Alder Reaction ◽  
Beta Particle ◽  
Clinical Tool ◽  
Inverse Electron Demand ◽  
Diels Alder Reaction ◽  
Positron Emission ◽  
Pretargeted Radioimmunotherapy ◽  
Therapy Studies

Over the past decade, theranostic imaging has emerged as a powerful clinical tool in oncology for identifying patients likely to respond to targeted therapies and for monitoring the response of patients to treatment. Herein, we report a theranostic approach to pretargeted radioimmunotherapy (PRIT) based on a pair of radioisotopes of copper: positron-emitting copper-64 (64Cu,t1/2= 12.7 h) and beta particle-emitting copper-67 (67Cu,t1/2= 61.8 h). This strategy is predicated on the in vivo ligation between a trans-cyclooctene (TCO)-bearing antibody and a tetrazine (Tz)-based radioligand via the rapid and bioorthogonal inverse electron-demand Diels–Alder reaction. Longitudinal therapy studies were conducted in a murine model of human colorectal carcinoma using an immunoconjugate of the huA33 antibody modified with TCO (huA33-TCO) and a67Cu-labeled Tz radioligand ([67Cu]Cu-MeCOSar-Tz). The injection of huA33-TCO followed 72 h later by the administration of 18.5, 37.0, or 55.5 MBq of [67Cu]Cu-MeCOSar-Tz produced a dose-dependent therapeutic response, with the median survival time increasing from 68 d for the lowest dose to >200 d for the highest. Furthermore, we observed that mice that received the highest dose of [67Cu]Cu-MeCOSar-Tz in a fractionated manner exhibited improved hematological values without sacrificing therapeutic efficacy. Dual radionuclide experiments in which a single administration of huA33-TCO was followed by separate injections of [64Cu]Cu-MeCOSar-Tz and [67Cu]Cu-MeCOSar-Tz revealed that the positron emission tomography images produced by the former accurately predicted the efficacy of the latter. In these experiments, a correlation was observed between the tumoral uptake of [64Cu]Cu-MeCOSar-Tz and the subsequent therapeutic response to [67Cu]Cu-MeCOSar-Tz.

10 Analysis of the in vivo course of foreign body response to a phycogenic bone substitute using FTIR spectroscopy

2021 ◽  
pp. 117-122
Author(s):  
Žarko Mitić ◽  
Sanja Stojanović ◽  
Stevo Najman ◽  
Mike Barbeck ◽  
Miroslav Trajanović
Keyword(s):  
Foreign Body ◽  
Ftir Spectroscopy ◽  
Bone Substitute ◽  
Foreign Body Response ◽  
Body Response

Mechanisms of Granulomatous Lung Disease from Inhaled Beryllium: The Role of Antigenicity in Granuloma Formation

1991 ◽  
Vol 19 (4_part_1) ◽  
pp. 514-525 ◽  
Author(s):  
Patrick J. Haley
Keyword(s):  
Foreign Body ◽  
Lung Disease ◽  
Molecular Mechanisms ◽  
Foreign Body Response ◽  
Immune Mediated ◽  
Granulomatous Lung Disease ◽  
Foreign Body Reactions ◽  
Similar Disease ◽  
Body Response

Granulomatous lung disease is a debilitating and sometimes fatal condition encountered in humans, for which the cellular and molecular mechanisms are poorly understood. Two patterns of granulomatous lung disease are recognized; foreign-body reactions and immune-mediated granulomas. Beryllium inhalation by humans results, in a small number of exposed individuals, in a chronic, granulomatous, immune-mediated pulmonary disease (chronic beryllium lung disease, CBD). Animal models used to study CBD have demonstrated significant species differences in the pathologic response to beryllium. While rats exposed to beryllium appear to develop a chronic, foreign-body response within the lung, dogs so exposed develop beryllium-specific immune responses within the lung and blood, accompanied by immune granulomas within the lung. At the heart of this difference appears to be the ability of the dog, but not the rat, to immunologically recognize the antigenicity of beryllium. This important difference further underscores the need to understand the mechanistic differences among similar disease syndromes, particularly if therapeutic regimens are to be used.

scholarly journals Immune‐Informed Mucin Hydrogels Evade Fibrotic Foreign Body Response In Vivo

2019 ◽  
Vol 29 (46) ◽  
pp. 1902581 ◽  
Author(s):  
Hongji Yan ◽  
Cédric Seignez ◽  
Morgan Hjorth ◽  
Benjamin Winkeljann ◽  
Matthew Blakeley ◽  
...  
Keyword(s):  
Foreign Body ◽  
Foreign Body Response ◽  
Body Response
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