scholarly journals Large Animal Studies to Reduce the Foreign Body Reaction in Brain–Computer Interfaces: A Systematic Review

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 275
Author(s):  
Shan Yasin Mian ◽  
Jonathan Roy Honey ◽  
Alejandro Carnicer-Lombarte ◽  
Damiano Giuseppe Barone

Brain–computer interfaces (BCI) are reliant on the interface between electrodes and neurons to function. The foreign body reaction (FBR) that occurs in response to electrodes in the brain alters this interface and may pollute detected signals, ultimately impeding BCI function. The size of the FBR is influenced by several key factors explored in this review; namely, (a) the size of the animal tested, (b) anatomical location of the BCI, (c) the electrode morphology and coating, (d) the mechanics of electrode insertion, and (e) pharmacological modification (e.g., drug eluting electrodes). Trialing methods to reduce FBR in vivo, particularly in large models, is important to enable further translation in humans, and we systematically reviewed the literature to this effect. The OVID, MEDLINE, EMBASE, SCOPUS and Scholar databases were searched. Compiled results were analysed qualitatively. Out of 8388 yielded articles, 13 were included for analysis, with most excluded studies experimenting on murine models. Cats, rabbits, and a variety of breeds of minipig/marmoset were trialed. On average, over 30% reduction in inflammatory cells of FBR on post mortem histology was noted across intervention groups. Similar strategies to those used in rodent models, including tip modification and flexible and sinusoidal electrode configurations, all produced good effects in histology; however, a notable absence of trials examining the effect on BCI end-function was noted. Future studies should assess whether the reduction in FBR correlates to an improvement in the functional effect of the intended BCI.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiaxi Chen ◽  
Huiqun Zhou ◽  
Daping Xie ◽  
Yiming Niu

Abstract Background Implantation of a biomaterial may induce the foreign-body reaction to the host tissue that determines the outcome of the integration and the biological performance of the implants. The foreign-body reaction can be modulated by control of the material properties of the implants. Methods First, we synthesized methacrylated Bletilla striata Polysaccharide (BSP-MA) and constructed a series of open porous cryogels utilizing this material via the freezing-thawing treatment of solvent-precursors systems. Second, Pore size and modulus were measured to characterize the properties of BSP cryogels. Live/dead staining of cells and CCK-8 were performed to test the cytocompatibility of the scaffolds. In addition, the Real-Time qPCR experiments were carried for the tests. Finally, the BSP scaffolds were implanted subcutaneously to verify the foreign-body reaction between host tissue and materials. Results Our data demonstrated that cryogels with different pore sizes and modulus can be fabricated by just adjusting the concentration. Besides, the cryogels showed well cytocompatibility in the in vitro experiments and exhibited upregulated expression levels of pro-inflammation-related genes (Tnfa and Il1b) with the increase of pore size. In vivo experiments further proved that with the increase of pore size, more immune cells infiltrated into the inner zone of materials. The foreign-body reaction and the distribution of immune-regulatory cells could be modulated by tuning the material microstructure. Conclusions Collectively, our findings revealed Bletilla striata polysaccharide cryogel scaffold with different pore sizes can spatially control foreign-body reaction. The microstructure of cryogels could differentially guide the distribution of inflammatory cells, affect the formation of blood vessels and fibrous capsules, which eventually influence the material-tissue integration. This work demonstrates a practical strategy to regulate foreign body reaction and promote the performance of medical devices.


2014 ◽  
Vol 7 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Amy S. Xue ◽  
John C. Koshy ◽  
William M. Weathers ◽  
Erik M. Wolfswinkel ◽  
Yoav Kaufman ◽  
...  

Biodegradable plates have been used extensively in fracture fixation since the 1960s. They rarely cause stress-protection atrophy or problems requiring secondary plate removal, common complications seen with metallic plates. However, aseptic foreign-body reactions have been reported, sometimes years after the original implantation. Both inadequate polymer degradation and debris accumulation have been implicated as causes. The current generation of commercial biodegradable plates is formulated to minimize this complication by altering the ratio of polylactic and polyglycolic acids. This in vivo study compares the degree of local foreign-body reaction of two commercially available resorbable plates in rabbits. Two types of biodegradable plates were examined: poly(D/L)lactide acid (PDLLA) and polylactide-co-glycolide acid (PLGA). Each plate was placed into a periosteal pericalvarial pocket created beneath the anterior or posterior scalp of a rabbit. Humane killing occurred at 3, 6, and 12 months postoperatively. Foreign-body reaction was evaluated histologically. The PDLLA plates demonstrated marked local foreign-body reactions within the implant capsule as early as 3 months after implantation, with presence of inflammatory cells and granulomatous giant cells in close association with the implant material. All local foreign-body reactions were subclinical with no corresponding tissue swelling requiring drainage. PLGA plates did not demonstrate any signs of inflammatory reactions. In addition, the PLGA plates did not appear to resorb or integrate at 12 months. Neither PDLLA nor PLGA plates demonstrated inflammation of the soft tissue or adjacent bone outside the implant capsule. In our study, the PDLLA plates demonstrated histological evidence of foreign-body reaction that is confined within the implant capsule, which was not seen with the PLGA plates. This finding may be attributable to the lack of significant resorption seen in the PLGA plates. Both PDLLA and PLGA plates were biocompatible with the rabbit tissue environment and should be considered for continued use in craniofacial, maxillofacial, and orthopedic reconstruction.


Author(s):  
V. A. Maksimenko ◽  
A. A. Harchenko ◽  
A. Lüttjohann

Introduction: Now the great interest in studying the brain activity based on detection of oscillatory patterns on the recorded data of electrical neuronal activity (electroencephalograms) is associated with the possibility of developing brain-computer interfaces. Braincomputer interfaces are based on the real-time detection of characteristic patterns on electroencephalograms and their transformation  into commands for controlling external devices. One of the important areas of the brain-computer interfaces application is the control of the pathological activity of the brain. This is in demand for epilepsy patients, who do not respond to drug treatment.Purpose: A technique for detecting the characteristic patterns of neural activity preceding the occurrence of epileptic seizures.Results:Using multi-channel electroencephalograms, we consider the dynamics of thalamo-cortical brain network, preceded the occurrence of an epileptic seizure. We have developed technique which allows to predict the occurrence of an epileptic seizure. The technique has been implemented in a brain-computer interface, which has been tested in-vivo on the animal model of absence epilepsy.Practical relevance:The results of our study demonstrate the possibility of epileptic seizures prediction based on multichannel electroencephalograms. The obtained results can be used in the development of neurointerfaces for the prediction and prevention of seizures of various types of epilepsy in humans. 


2007 ◽  
Vol 330-332 ◽  
pp. 193-196
Author(s):  
Duck Hyun Kim ◽  
Kang Sik Lee ◽  
Jung Hwa Kim ◽  
Jae Suk Chang ◽  
Yung Tae Kim

We observed the cytotoxicity of human bone marrow stromal cells(hBMSCs) by microparticles of bioactive glass with four particle groups(same chemical composition-45S5 but produced by two different manufacturer and two different size groups). In vivo test using rat calvaria were also carried out. The apoptosis rates of all small particle groups(10-20 ㎛) were increased than large(500-700 ㎛ or 200-900 ㎛) particle groups in any culture time and any amount of particles with statistical significance. In vivo study we observed pathologic signs such as macrophages and foreign-body giant cells in rat calvaria by micro-particles of bioglass. Small(10- 20 ㎛) sized particles induced foreign body reaction and bone resorption. There was proliferation of macrophages and cells in large number. But in large particle groups, only fibroblasts were surrounding the particles. The micro-particles of bioglass induced apoptosis of hBMSC and foreign body reaction in calvaria of rat, therefore micro-particles of bioglass may cause osteolysis if used in replacement arthroplasty.


2018 ◽  
Author(s):  
Xinze Peng ◽  
Mia R. Maltz ◽  
Jon K. Botthoff ◽  
Emma L. Aronson ◽  
Tara M. Nordgren ◽  
...  

Air pollution poses a significant threat to the environment and human health. Most in-vivo health studies conducted regarding air pollutants, including particulate matter (PM) and gas phase pollutants, have been either through traditional medical intranasal treatment or using a tiny chamber, which limit animal activities. In this study, we designed and tested a large, whole-body, multiple animal exposure chamber with uniform dispersion and exposure stability for animal studies. The chamber simultaneously controls particle size distribution and PM mass concentration. Two different methods were used to generate aerosol suspension through either soluble material (Alternaria extract), liquid particle suspension (Nanosilica solution) or dry powder (silica powder). We demonstrate that the chamber system provides well controlled and characterized whole animal exposures, where dosage is by inhalation of particulate matter.


2019 ◽  
Author(s):  
Alejandro Carnicer-Lombarte ◽  
Damiano G. Barone ◽  
Ivan B. Dimov ◽  
Russell S. Hamilton ◽  
Malwina Prater ◽  
...  

AbstractMedical implants offer a unique and powerful therapeutic approach in many areas of medicine. However, their lifetime is often limited as they may cause a foreign body reaction (FBR) leading to their encapsulation by scar tissue1–4. Despite the importance of this process, how cells recognise implanted materials is still poorly understood5, 6. Here, we show how the mechanical mismatch between implants and host tissue leads to FBR. Fibroblasts and macrophages, which are both crucially involved in mediating FBR, became activated when cultured on materials just above the stiffness found in healthy tissue. Coating implants with a thin layer of hydrogel or silicone with a tissue-like elastic modulus of ∼1 kPa or below led to significantly reduced levels of inflammation and fibrosis after chronic implantation both in peripheral nerves and subcutaneously. This effect was linked to the nuclear localisation of the mechanosensitive transcriptional regulator YAP in vivo. Hence, we identify the mechanical mismatch between implant and tissue as a driver of FBR. Soft implant coatings matching the mechanical properties of host tissue minimized FBR and may be used as a novel therapeutic strategy to improve long-term biomedical implant stability without extensive modification of current implant manufacturing techniques, thus facilitating clinical translation.One sentence summaryForeign body reaction to medical implants can be avoided by matching the stiffness of the implant surface to that of the host tissue.


1998 ◽  
Vol 45 (7) ◽  
pp. 921-927 ◽  
Author(s):  
H.H. Qiu ◽  
L.W. Hedlund ◽  
M.R. Neuman ◽  
C.R. Edwards ◽  
R.D. Black ◽  
...  

1988 ◽  
Vol 7 (4) ◽  
pp. 469-479 ◽  
Author(s):  
James M. Anderson

The goal of in vivo testing of a medical device is to determine the safety or biocompatibility of the device in a biological environment. Biocompatibility is the ability of a medical device to perform with an appropriate host response in a specific application. Biocompatibility assessment is considered to be a measure of the magnitude and duration of adverse alterations in homeostatic mechanisms that determine the host response. Perspectives are provided on the role of injury, tissue responses to medical devices, and blood responses to medical devices. The concept of the normal foreign body reaction is presented. The potential importance of the macrophage, an important component of the foreign body reaction, in controlling the biocompatibility in the in vivo environment is discussed.


2016 ◽  
Vol 310 (9) ◽  
pp. H1045-H1054 ◽  
Author(s):  
David C. Zebrowski ◽  
Robert Becker ◽  
Felix B. Engel

In recent years, there has been a dramatic increase in research aimed at regenerating the mammalian heart by promoting endogenous cardiomyocyte proliferation. Despite many encouraging successes, it remains unclear if we are any closer to achieving levels of mammalian cardiomyocyte proliferation for regeneration as seen during zebrafish regeneration. Furthermore, current cardiac regenerative approaches do not clarify whether the induced cardiomyocyte proliferation is an epiphenomena or responsible for the observed improvement in cardiac function. Moreover, due to the lack of standardized protocols to determine cardiomyocyte proliferation in vivo, it remains unclear if one mammalian regenerative factor is more effective than another. Here, we discuss current methods to identify and evaluate factors for the induction of cardiomyocyte proliferation and challenges therein. Addressing challenges in evaluating adult cardiomyocyte proliferation will assist in determining 1) which regenerative factors should be pursued in large animal studies; 2) if a particular level of cell cycle regulation presents a better therapeutic target than another (e.g., mitogenic receptors vs. cyclins); and 3) which combinatorial approaches offer the greatest likelihood of success. As more and more regenerative studies come to pass, progress will require a system that not only can evaluate efficacy in an objective manner but can also consolidate observations in a meaningful way.


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