Material-mediated pyrogens in medical devices: Applicability of the in vitro Monocyte Activation Test

Borton, L. K.

doi:10.14573/altex.1709221

Cited by 14 publications

(12 citation statements)

References 19 publications

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“…A distinctive feature of the line of monocytes-macrophages is plasticity, which turns them into an adaptive component of innate immunity (Locati et al, 2013). In vitro monocyte activation test (MAT) is widely used to assess the pyrogenic activity of medical materials and detect substances that activate human monocytes to release cytokines (Borton and Coleman, 2018). THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport.…”

Section: Immunogenic Properties Of Decmmentioning

confidence: 99%

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine.

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Section: Immunogenic Properties Of Decmmentioning

confidence: 99%

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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“…Workshop participants discussed the process of developing a MDDT to validate the MAT as a replacement for the RPT and/or LAL with input from CDRH attendees on the agency's critical needs. Borton and Coleman (2018) proposed the following definition for MMPs: "any exogenous non-biological substance known to cause a febrile response. This definition excludes substances such as endogenous chemicals (i.e., cytokines and prostaglandins), fungi, yeast, viruses, bacteria, and parasites."…”

Section: Cdrh Medical Device Development Tools Programmentioning

confidence: 99%

“…The list, which was reaffirmed recently by ISO/TC 194 WG 16, includes: -prostaglandin; -inducers (e.g., polyadenylic, polyuridylic, polybionosinic and polyribocytidylic acids); -substances disrupting the function of thermoregulatory centers (e.g., LSD, cocaine, morphine); -uncoupling agents of oxidative phosphorylation (e.g., 4, 6-dinitro-o-cresol, dinitrophenol, picric acid); -N-phenyl-β-naphthylamine and aldo-α-naphthylamine (the febrile mechanism is unknown); -neurotransmitters (e.g., noradrenaline, serotonin); and -metals such as nickel salts, in some instances. However, the relevance of MMPs in pyrogen testing of medical devices, and whether any of the pyrogen tests can detect these substances, is disputed (Borton and Coleman, 2018). The relevance of material-mediated pyrogenicity is debatable as the list of chemicals includes substances that should not be found in many medical devices.…”

Section: Cdrh Medical Device Development Tools Programmentioning

confidence: 99%

Using the monocyte activation test as a stand-alone release test for medical devices

Brown¹,

Clippinger²,

Briglia³

et al. 2021

ALTEX

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Monocyte activation tests (MAT) are widely available but rarely used in place of animal-based pyrogen tests for safety assessment of medical devices. To address this issue, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods and the PETA International Science Consortium Ltd. convened a workshop at the National Institutes of Health on September 18-19, 2018. Participants included representatives from MAT testing laboratories, medical device manufacturers, the U.S. Food and Drug Administration’s Center for Devices and Radiologic Health (CDRH), the U.S. Pharmacopeia, the International Organization for Standardization, and experts in the development of MAT protocols. Discussions covered industry experiences with the MAT, remaining challenges, and how CDRH’s Medical Device Development Tools (MDDT) Program, which qualifies tools for use in evaluating medical devices to streamline device development and regulatory evaluation, could be a pathway to qualify the use of MAT in place of the rabbit pyrogen test and the limulus amebocyte lysate test for medical device testing. Workshop outcomes and follow-up activities are discussed.

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“…Исследовали возможность применения МАТ для проверки нейрохирургических имплантатов, а именно зажимов аневризмы. Благодаря непосредственному контакту исследуемого материала с клетками крови в этом тесте не нужно оценивать смыв с поверхности образца, при выполнении которого возможно получение неоднозначных результатов [10][11][12]. Непосредственное определение пирогенов -это одно из важных преимуществ МАТ перед методикой определения с помощью ЛАЛ-теста.…”

Section: оригинальные статьи / Original Articlesunclassified

Detection of Pyrogens in Hormonal Implants Using the LAL Test

Неугодова¹,

Shapovalova²,

Сапожникова³

et al. 2021

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

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The State Pharmacopoeia of the Russian Federation, 14th edition states that implants are a sterile dosage form, and have to be tested for pyrogens. However, it does not provide details on how the test should be performed for this dosage form.The aim of the study was to develop a LAL test procedure for detection of bacterial endotoxins (BE) in implants, using the example of a goserelin product.Materials and methods: BE extraction from the implant surface into an aqueous medium was performed with subsequent BE detection in the extract by turbidimetric kinetic test. The implant was then dissolved in dimethyl sulfoxide, and the obtained goserelin solution was tested for BEs using the gel-clot test.Results: the analysis of the Russian and foreign pharmacopoeial approaches to pyrogenic substance detection in hormonal implants helped to develop two sample preparation procedures for determination of BE content (in the extract and the implant solution). It was demonstrated that the BE content in the water extract did not exceed 0.01 EU/mL and was less than 0.07 EU per implant. The BE content in the implant solution was less than 8.3 EU per 1 mg of goserelin, which is almost eleven-fold lower than the theoretically-derived limit.Conclusions: the authors developed two test procedures for BE detection in hormonal implants using the LAL test, which could be included in manufacturers’ product files. The first procedure involves testing of the water extract from the implant surface and establishes the BE limit of no more than 20 EU/product. The second procedure involves complete dissolution of the implant in dimethyl sulfoxide and establishes the limit of not more than 97.22 EU per 1 mg of goserelin.

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Material-mediated pyrogens in medical devices: Applicability of the in vitro Monocyte Activation Test

Cited by 14 publications

References 19 publications

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Using the monocyte activation test as a stand-alone release test for medical devices

Detection of Pyrogens in Hormonal Implants Using the LAL Test

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