scholarly journals Minimally Invasive Precise Application of Bioadhesives to Prevent IPPROM on a Pregnant Sheep Model

2021 ◽  
pp. 1-9
Author(s):  
Yannick R. Devaud ◽  
Senta Stäuble ◽  
Ueli Moehrlen ◽  
Miriam Weisskopf ◽  
Ladina Vonzun ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Negative Control ◽  
Fetal Membrane ◽  
Tissue Adhesives ◽  
Amniotic Cavity ◽  
Sheep Model ◽  
Preterm Premature Rupture ◽  
Post Surgery ◽  
Pregnant Sheep

<b><i>Introduction:</i></b> Iatrogenic preterm premature rupture of the membrane remains the Achille’s heel of fetoscopy. The aim of this study was to show in vivo feasibility of fetal membrane (FM) defect sealing by the application of tissue glues with umbrella-shaped receptors. <b><i>Methods:</i></b> First, we adapted our previously described ex vivo strategy and evaluated the adhesion strength of different tissue glues, Histoacryl® and Glubran2®, by bonding polytetrafluoroethylene or silicone encapsulated nitinol glue receptor to human FM. Then, we exposed pregnant sheep uterus through a laparotomy and placed a 10-French trocar into the amniotic cavity through which the umbrella-shaped glue receptor (<i>n</i> = 9) was inserted and fixated onto the FM with the tissue glues (<i>n</i> = 8). The tightness of the sealed defects was assessed 4 h post-surgery. <b><i>Results:</i></b> Both tissue glues tested resulted in adhesion of the glue receptors to the FM ex vivo. In vivo, all glue receptors opened in the amniotic cavity (<i>n</i> = 9) and all successfully placed glue receptors sealed the FM defect (<i>n</i> = 8). Four hours post-surgery, 2 treatment sites showed minimal leakage whereas the negative control without glue (<i>n</i> = 1) showed substantial leakage. <b><i>Discussion:</i></b> This in vivo study confirms that fetoscopically induced FM defects can be sealed by the application of tissue adhesives.

scholarly journals Optimizing cisplatin delivery to triple-negative breast cancer through novel EGFR aptamer-conjugated polymeric nanovectors

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Lisa Agnello ◽  
Silvia Tortorella ◽  
Annachiara d’Argenio ◽  
Clarissa Carbone ◽  
Simona Camorani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Ex Vivo ◽  
Treatment Options ◽  
Negative Control ◽  
Therapeutic Effects ◽  
Metastatic Setting

Abstract Background Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC. Methods Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses. Results We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs. Conclusions Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 861
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

About Puncture Testing Applied for Mechanical Characterization of Fetal Membranes

2014 ◽  
Vol 136 (11) ◽  
Author(s):  
Wilfried Bürzle ◽  
Edoardo Mazza ◽  
John J. Moore
Keyword(s):  
Deformation Behavior ◽  
Mechanical Characterization ◽  
Ex Vivo ◽  
Fetal Membrane ◽  
Membrane Rupture ◽  
Resistance To Deformation ◽  
Ex Vivo Testing ◽  
Insight Into

Puncture testing has been applied in several studies for the mechanical characterization of human fetal membrane (FM) tissue, and significant knowledge has been gained from these investigations. When comparing results of mechanical testing (puncture, inflation, and uniaxial tension), we have observed discrepancies in the rupture sequence of FM tissue and significant differences in the deformation behavior. This study was undertaken to clarify these discrepancies. Puncture experiments on FM samples were performed to reproduce previous findings, and numerical simulations were carried out to rationalize particular aspects of membrane failure. The results demonstrate that both rupture sequence and resistance to deformation depend on the samples' fixation. Soft fixation leads to slippage in the clamping, which reduces mechanical loading of the amnion layer and results in chorion rupturing first. Conversely, the stiffer, stronger, and less extensible amnion layer fails first if tight fixation is used. The results provide a novel insight into the interpretation of ex vivo testing as well as in vivo membrane rupture.

TTP889, a Novel Orally Active Partial Inhibitor of FIXa Inhibits Clotting in Two A/V Shunt Models without Prolonging Bleeding Times.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1886-1886 ◽  
Author(s):  
Robert Rothlein ◽  
Jane M. Shen ◽  
Najih Naser ◽  
Devi R. Gohimukkula ◽  
Thomas B. Caligan ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Anticoagulant Activity ◽  
Clot Formation ◽  
Once Daily ◽  
Post Surgery ◽  
Novel Approach ◽  
Clotting Cascade ◽  
Orally Active ◽  
Coagulation Pathway

Abstract Based on previous studies showing the efficacy of FactorIXa (FIXa) blockade using an active site-blocked form of this coagulation enzyme, we speculated that partial inhibition of the intrinsic coagulation pathway would offer a novel approach to attenuate intravascular clot formation without promoting untoward bleeding. Here we describe the anticoagulant activity of TTP889, a small molecule partial inhibitor of FIXa activity. TTP889 is orally absorbed with a PK profile that is conducive to once daily dosing. It is selective for FIXa in that it shows little to no activity against several other proteases in the clotting cascade including FXa, FXIa, FXIIa or FVIIa in a unique clotting assay. In vivo, TTP889 inhibited fibrin deposition in a rat arteriovenous (A/V) shunt model. In this model, vehicle treated rats had 104mg ± 43 of fibrin deposited on a silk thread after a 15 minute shunt while TTP889 treated rats had significantly less fibrin deposited (39mg ± 18 p=<0.001). Furthermore, TTP889 inhibited clotting in a porcine A/V shunt model where pressure across a hemodialysis filter that was shunting the carotid artery to the jugular vein was used as an indirect marker of clot formation. In this model, TTP889 at 0.3mg/kg performed as well as 150U/kg of heparin over the 90-minute shunt. Of additional importance, TTP889 has no effect on bleeding times as measured by APTT or ACT assays ex-vivo or by bleeding time and volume from incisions in the skin or spleen in vivo. Together, these data support that TTP889 is a selective partial inhibitor of FIXa activity that offers a novel approach to attenuate clot formation associated with intravascular clotting without promoting untoward bleeding. TTP 889 is currently in Phase II and is being evaluated for the prevention of DVT in hip fracture patients with treatment starting one week post surgery and continued for 3 weeks.

scholarly journals A mussel-inspired film for adhesion of wet buccal tissue and efficient buccal drug delivery

2020 ◽  
Author(s):  
Shanshan Hu ◽  
Xibo Pei ◽  
Lunliang Duan ◽  
Zhou Zhu ◽  
Yanhua Liu ◽  
...  
Keyword(s):  
Erosion Rate ◽  
Ex Vivo ◽  
Covalent Bonding ◽  
Buccal Delivery ◽  
Tissue Adhesives ◽  
Drug Bioavailability ◽  
Buccal Drug Delivery ◽  
Strong Adhesion ◽  
Developing System

Abstract Administration of drug via the buccal route has attracted much attention in recent years. However, developing system with satisfactory adhesion in wet conditions and drug bioavailability still remains a challenge. Here, we propose a mussel inspired mucoadhesive film. Ex vivo porcine and in vivo rat models show that the film can achieve strong adhesion with wet buccal tissues. We also demonstrate that the film exhibits tunable mucoadhesion strength and erosion rate. The adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Then, polydopamine (PDA) modified nanoparticles (NPs) are incorporated into the film and the PDA NPs loaded films show superior advantages to transport across multiple barriers of buccal mucosa with improved drug bioavailability and therapeutic efficacy in oral mucositis models. We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.

scholarly journals In Vivo Study of Osteochondral Defect Regeneration Using Innovative Composite Calcium Phosphate Biocement in a Sheep Model

Materials ◽  
2021 ◽  
Vol 14 (16) ◽  
pp. 4471
Author(s):  
Lenka Kresakova ◽  
Jan Danko ◽  
Katarina Vdoviakova ◽  
Lubomir Medvecky ◽  
Zdenek Zert ◽  
...  
Keyword(s):  
Amino Acids ◽  
Calcium Phosphate ◽  
Osteochondral Defect ◽  
Articular Surface ◽  
Fibrous Tissue ◽  
Treated Group ◽  
Negative Control ◽  
Osteochondral Defects ◽  
Sheep Model

This study aimed to clarify the therapeutic effect and regenerative potential of the novel, amino acids-enriched acellular biocement (CAL) based on calcium phosphate on osteochondral defects in sheep. Eighteen sheep were divided into three groups, the treated group (osteochondral defects filled with a CAL biomaterial), the treated group with a biocement without amino acids (C cement), and the untreated group (spontaneous healing). Cartilages of all three groups were compared with natural cartilage (negative control). After six months, sheep were evaluated by gross appearance, histological staining, immunohistochemical staining, histological scores, X-ray, micro-CT, and MRI. Treatment of osteochondral defects by CAL resulted in efficient articular cartilage regeneration, with a predominant structural and histological characteristic of hyaline cartilage, contrary to fibrocartilage, fibrous tissue or disordered mixed tissue on untreated defect (p < 0.001, modified O’Driscoll score). MRI results of treated defects showed well-integrated and regenerated cartilage with similar signal intensity, regularity of the articular surface, and cartilage thickness with respect to adjacent native cartilage. We have demonstrated that the use of new biocement represents an effective solution for the successful treatment of osteochondral defects in a sheep animal model, can induce an endogenous regeneration of cartilage in situ, and provides several benefits for the design of future therapies supporting osteochondral defect healing.

scholarly journals Optimizing Cisplatin Delivery to Triple-negative Breast Cancer through Novel EGFR Aptamer-conjugated Polymeric Nanovectors

2021 ◽  
Author(s):  
Lisa Agnello ◽  
Silvia Tortorella ◽  
Annachiara d'Argenio ◽  
Clarissa Carbone ◽  
Simona Camorani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Targeting ◽  
Triple Negative ◽  
Ex Vivo ◽  
Treatment Options ◽  
Negative Control ◽  
Therapeutic Effects ◽  
Metastatic Setting

Abstract Background: Management of triple-negative breast cancer (TNBC) is still challenging because of its aggressive clinical behavior and limited targeted treatment options. Cisplatin represents a promising chemotherapeutic compound in neoadjuvant approaches and in the metastatic setting, but its use is limited by scarce bioavailability, severe systemic side effects and drug resistance. Novel site-directed aptamer-based nanotherapeutics have the potential to overcome obstacles of chemotherapy. In this study we investigated the tumor targeting and the anti-tumorigenic effectiveness of novel cisplatin-loaded and aptamer-decorated nanosystems in TNBC.Methods: Nanotechnological procedures were applied to entrap cisplatin at high efficacy into polymeric nanoparticles (PNPs) that were conjugated on their surface with the epidermal growth factor receptor (EGFR) selective and cell-internalizing CL4 aptamer to improve targeted therapy. Internalization into TNBC MDA-MB-231 and BT-549 cells of aptamer-decorated PNPs, loaded with BODIPY505-515, was monitored by confocal microscopy using EGFR-depleted cells as negative control. Tumor targeting and biodistribution was evaluated by fluorescence reflectance imaging upon intravenously injection of Cyanine7-labeled nanovectors in nude mice bearing subcutaneous MDA-MB-231 tumors. Cytotoxicity of cisplatin-loaded PNPs toward TNBC cells was evaluated by MTT assay and the antitumor effect was assessed by tumor growth experiments in vivo and ex vivo analyses.Results: We demonstrate specific, high and rapid uptake into EGFR-positive TNBC cells of CL4-conjugated fluorescent PNPs which, when loaded with cisplatin, resulted considerably more cytotoxic than the free drug and nanovectors either unconjugated or conjugated with a scrambled aptamer. Importantly, animal studies showed that the CL4-equipped PNPs achieve significantly higher tumor targeting efficiency and enhanced therapeutic effects, without any signs of systemic toxicity, compared with free cisplatin and untargeted PNPs.Conclusion: Our study proposes novel and safe drug-loaded targeted nanosystems for EGFR-positive TNBC with excellent potential for the application in cancer diagnosis and therapy.

scholarly journals Cognitive-Enhancing, Ex Vivo Antilipid Peroxidation and Qualitative Phytochemical Evaluation of the Aqueous and Methanolic Stem Bark Extracts of Lonchocarpus eriocalyx (Harms.)

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Gervason Moriasi ◽  
Anthony Ireri ◽  
Mathew Ngugi
Keyword(s):  
Cognitive Impairment ◽  
Plant Extracts ◽  
Cognitive Deficits ◽  
Ex Vivo ◽  
Negative Control Group ◽  
Negative Control ◽  
Scientific Data ◽  
Control Group ◽  
Isolation And Characterization

Over 50 million persons are living with cognitive deficits worldwide, with over 80% of these individuals living in the developing world. The number of affected persons is projected to go over 152 million by the year 2050. Current drugs used for cognitive impairment are debatably ineffective, costly, inaccessible, and associated with undesirable events that call for the search for alternative and complementary approaches. Plants are arguably affordable, accessible, and efficacious. However, despite the reported healing claims, scientific data validating these claims are lacking. L. eriocalyx is traditionally used for the management of various conditions, including cognitive impairment but has not been scientifically explored. In this study, the Morris Water Maze (MWM) method was used to evaluate in vivo cognitive-enhancing effects of studied extracts of L. eriocalyx. Furthermore, following MWM experiments, brains were dissected and processed, and malondialdehyde profiles were determined. Qualitative phytochemical profiles of the studied plant extracts were also determined. The results showed that mice that were treated with the studied plant extracts took significantly shorter transfer latencies, navigation distances, and significantly longer latencies in the target quadrant (NW) ( p < 0.05 ) compared with the negative control mice, indicating cognitive-enhancing activities. Furthermore, cognitively impaired mice that received the studied plant extracts had significantly lower MDA profiles compared with the MDA profile of the negative control group mice ( p < 0.05 ). The cognitive-enhancing and MDA profile lowering effects were attributed to the presence of antioxidant phytoconstituents that ought to have modulated the redox state, thereby attenuating brain damage. These extracts can be, therefore, used for the management of cognitive deficits. Further studies leading to isolation and characterization of active molecules for cognitive impairment are recommended. Furthermore, the precise mechanism(s) through which these extracts exert their pharmacologic activity should be established.

Bioactive Calcium Phosphate Material for Dental Endodontic Treatment. Root Apical Deposition.

2006 ◽  
Vol 309-311 ◽  
pp. 1157-1160 ◽  
Author(s):  
Julia Bosco ◽  
Bénedicte Enkel ◽  
Valerie Armengol ◽  
G. Daculsi ◽  
Alain Jean ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Bone Substitute ◽  
Ex Vivo ◽  
Human Model ◽  
Mineral Formation ◽  
Ceramic Suspension ◽  
Calcium Phosphate Ceramic ◽  
Sheep Model ◽  
Good Filling

An injectable bone substitute (IBS) made of a suspension of Calcium phosphate ceramic was used to filled dental root canal after removing of canal pulp. The aim of this study was to verify the ability of calcium phosphate ceramic suspension to fill the apical zone of teeth ex vivo (n=40) and in vivo in a sheep model (n=8). The results showed that injection is possible with a good level of BCP granules at the end of the root dental canal with extracted tooth. In vivo, the presence of blood pressure due to the pulpectomy is a negative parameter to allow a good filling. The scanning electron microscopy revealed mineral formation at the apex level with mineral tissue conduction between the BCP granules but only one tooth showed a good apical filling with a good sealing. The sealing of the apex seems to depend of the amount of BCP granules. Other experiments with other animal models closer to a Human model have to be performed before human trials.

scholarly journals In Vivo Cognitive-Enhancing, Ex Vivo Malondialdehyde-Lowering Activities and Phytochemical Profiles of Aqueous and Methanolic Stem Bark Extracts of Piliostigma thonningii (Schum.)

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Gervason Apiri Moriasi ◽  
Anthony Muriithi Ireri ◽  
Mathew Piero Ngugi
Keyword(s):  
Cognitive Impairment ◽  
Plant Extracts ◽  
Ex Vivo ◽  
Herbal Medicines ◽  
Thiobarbituric Acid ◽  
Stem Bark ◽  
Negative Control ◽  
Scientific Data ◽  
Contributing Factors

Cognitive impairment (CI) is among the leading causes of disability in humans. It is estimated that over 35.6 million people are suffering from Alzheimer’s disease- (AD-) associated cognitive deficits globally with these statistics projected to rise over 115.4 million by the year 2050. There is no specific etiology for this cognitive impairment; however, various contributing factors including advancing age (>60 years old), oxidative stress, cerebral injuries, infections, neurologic disorders, and cancer have been implicated. Despite various attempts to manage CI, no curative medicines are yet available. The current drugs used to manage symptoms of AD-associated CI including Donepezil and Rivastigmine among others are only palliative rather than therapeutic. Furthermore, these agents have been associated with undesirable side effects. This calls for alternative and complementary approaches aimed at either preventing or reverting AD-related CI in a curative way without causing adverse events. It is estimated that over 80% of the world’s population utilize herbal medicines for basic healthcare as it is considered safe, affordable, and easily accessible as opposed to conventional healthcare. Various parts of P. thonningii are used in traditional medicine to manage various conditions including CI. However, empirical and scientific data to validate these uses is lacking. In this study, the Morris water maze (MWM) experiment was adopted to evaluate the cognitive-enhancing effects of the studied plant extracts. The malondialdehyde (MDA) profiles in the brains of experimental mice were determined using the thiobarbituric acid reactive substances (TBARS) test. Moreover, qualitative phytochemical profiling of the studied plant extracts was performed using standard procedures. The results showed remarkable cognitive-enhancing activities which were reflected in significantly shorter transfer latencies, navigation distances, longer time spent in platform quadrant, and lower MDA levels compared with those recorded for the negative control mice (p<0.05). Phytochemical screening of the studied plant extracts revealed the presence of antioxidant phytocompounds, which may have played key roles in the extracts’ potency. Based on the findings herein, P. thonningii extracts, especially the aqueous ones have a promising potential for the management of AD-associated CI. Further studies aimed at isolating and characterizing specific active compounds for CI from P. thonningii are recommended. Additionally, specific mode(s) of action of active principles should be elucidated. Moreover, toxicity studies should be done on the studied plant extracts to ascertain their safety.

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