scholarly journals On the in Vitro Biocompatibility Testing of Bioactive Glasses

Materials ◽  
2020 ◽  
Vol 13 (8) ◽  
pp. 1816 ◽  
Author(s):  
Devis Bellucci ◽  
Elena Veronesi ◽  
Massimo Dominici ◽  
Valeria Cannillo

In this work, a new 3D cellular model—based on human bone marrow mesenchymal stem cells (BM–MSCs)—was used for the first time to test the 45S5 Bioglass® (45S5). Such a model, previously used to evaluate the biologic performance of two novel bioactive glasses, suggested out the regenerative potential of such materials. In fact, BM–MSCs were able both to adhere and colonize the biomaterials, as well as differentiate toward osteoblasts—even in absence of specific growth factors. Surprisingly, BM–MSCs were not able to colonize 45S5 granules (almost no adhesion and/or colonization was observed), and thus, were not capable of providing any osteogenic differentiation. Therefore, the model seems to suggest that the two novel bioactive glasses have a better biologic performance than 45S5. If this hypothesis is confirmed also by in vivo tests, the 3D model may become a predictive tool for discriminating between different potential bioactive materials by comparatively evaluating them, and preliminarily selecting the best ones in relation to their biocompatibility potential—before proceeding with further experiments in vivo. This approach could favor the reduction of costs and time of pre-clinical and clinical trials.

2021 ◽  
Vol 7 (2) ◽  
pp. 621-624
Author(s):  
Valeria Khaimov ◽  
Bastian-Jesper Klußmann-Fricke ◽  
Sabine Illner ◽  
Stefan Siewert ◽  
Klaus-Peter Schmitz

Abstract Biomaterial research efforts focus on the development of biomaterials that mimic the natural extracellular environment. In addition, different strategies are applied to render materials for blood-contacting devices nonthrombogenic through surface modifications that would suppress activation of platelets, coagulation and the complement system. A confluent thin layer of endothelial cells lines all blood vessels and produces factors responsible for inhibition of coagulation, thrombosis and neointimal hyperplasia. Thus, the ability to rapidly form a healthy endothelium upon implantation represents a desired property of biomaterials used for cardiovascular devices. In this study we used advanced in vitro methods to investigate the biocompatibility of a biodegradable and a permanent electrospun nanofiber fabric, poly-L-lactic acid and polycarbonate-based silicone elastomer respectively, with the focus on endothelialization and hemocompatibility.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 819
Author(s):  
Nicolai Rügen ◽  
Timothy P. Jenkins ◽  
Natalie Wielsch ◽  
Heiko Vogel ◽  
Benjamin-Florian Hempel ◽  
...  

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.


2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tong Chen ◽  
Qiang Chu ◽  
Mengyang Li ◽  
Gaorong Han ◽  
Xiang Li

AbstractElectrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jakob Weglage ◽  
Friederike Wolters ◽  
Laura Hehr ◽  
Jakob Lichtenberger ◽  
Celina Wulz ◽  
...  

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Callizot ◽  
C. Estrella ◽  
S. Burlet ◽  
A. Henriques ◽  
C. Brantis ◽  
...  

AbstractProgranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengchuan Zhang ◽  
Ruogu Xu ◽  
Yang Yang ◽  
Chaoan Liang ◽  
Xiaolin Yu ◽  
...  

Abstract Background Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo. Results We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation. Conclusions These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.


Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3337
Author(s):  
Sara Hooshmand ◽  
Sahar Mollazadeh ◽  
Negar Akrami ◽  
Mehrnoosh Ghanad ◽  
Ahmed El-Fiqi ◽  
...  

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.


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