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
2021 ◽  
pp. 117-122
Author(s):  
Žarko Mitić ◽  
Sanja Stojanović ◽  
Stevo Najman ◽  
Mike Barbeck ◽  
Miroslav Trajanović

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

Author(s):  
Andrea Jaquins-Gerstl ◽  
Adrian C. Michael

Microdialysis probes, electrochemical microsensors, and neural prosthetics are often used for in vivo monitoring, but these are invasive devices that are implanted directly into brain tissue. Although the selectivity, sensitivity, and temporal resolution of these devices have been characterized in detail, less attention has been paid to the impact of the trauma they inflict on the tissue or the effect of any such trauma on the outcome of the measurements they are used to perform. Factors affecting brain tissue reaction to the implanted devices include: the mechanical trauma during insertion, the foreign body response, implantation method, and physical properties of the device (size, shape, and surface characteristics. Modulation of the immune response is an important step toward making these devices with reliable long-term performance. Local release of anti-inflammatory agents such as dexamethasone (DEX) are often used to mitigate the foreign body response. In this article microdialysis is used to locally deliver DEX to the surrounding brain tissue. This work discusses the immune response resulting from microdialysis probe implantation. We briefly review the principles of microdialysis and the applications of DEX with microdialysis in (i) neuronal devices, (ii) dopamine and fast scan cyclic voltammetry, (iii) the attenuation of microglial cells, (iv) macrophage polarization states, and (v) spreading depolarizations. The difficulties and complexities in these applications are herein discussed.


Biomaterials ◽  
2012 ◽  
Vol 33 (29) ◽  
pp. 6926-6932 ◽  
Author(s):  
Ivonne Bartsch ◽  
Elmar Willbold ◽  
Sergey Yarmolenko ◽  
Frank Witte

Author(s):  
Claire E. Witherel ◽  
Kimheak Sao ◽  
Becky K. Brisson ◽  
Biao Han ◽  
Susan W. Volk ◽  
...  

AbstractAberrant extracellular matrix (ECM) assembly surrounding implanted biomaterials is the hallmark of the foreign body response, in which implants become encapsulated in thick fibrous tissue that prevents their proper function. While macrophages are known regulators of fibroblast behavior, how their phenotype influences ECM assembly and the progression of the foreign body response is poorly understood. In this study, we used in vitro models with physiologically relevant macrophage phenotypes, as well as controlled release of macrophage-modulating cytokines from gelatin hydrogels implanted subcutaneously in vivo to investigate the role of macrophages in ECM assembly. Primary human macrophages were polarized to four distinct phenotypes, which have each been associated with fibrosis, including pro-inflammatory M1, pro-healing M2, and a hybrid M1/M2, generated by exposing macrophages to M1- and M2-promoting stimuli simultaneously. Additionally, macrophages were first polarized to M1 and then to M2 (M1→M2) to generate a phenotype typically observed during normal wound healing. Human dermal fibroblasts that were cultured in macrophage-conditioned media upregulated numerous genes involved in regulation of ECM assembly, especially in M2-conditioned media. Hybrid M1/M2 macrophage-conditioned media caused fibroblasts to produce a matrix with thicker and less aligned fibers, while M2 macrophage-conditioned media caused the formation of a more aligned matrix with thinner fibers. Gelatin methacrylate hydrogels containing interleukin-4 (IL4) and IL13-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles were designed to promote the M2 phenotype in a murine subcutaneous in vivo model. NanoString multiplex gene expression analysis of hydrogel explants showed that hydrogels with and without drug caused markers of both M1 and M2 phenotypes to be highly expressed, but the release of IL4+IL13 promoted upregulation of M2 markers and genes associated with regulation of ECM assembly, such as Col5a1 and Col6a1. Biochemical analysis and second harmonic generation microscopy showed that the release of IL4+IL13 increased total sulfated glycosaminoglycan content and decreased fibril alignment, which is typically associated with less fibrotic tissue. Together, these results show that hybrid M1/M2 macrophages regulate ECM assembly, and that shifting the balance towards M2 may promote architectural and compositional changes in ECM with enhanced potential for downstream remodeling.


2019 ◽  
Author(s):  
Hongji Yan ◽  
Cédric Seignez ◽  
Morgan Hjorth ◽  
Benjamin Winkeljann ◽  
Oliver Lieleg ◽  
...  

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.


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