scholarly journals Thermo-Responsive Hydrogels Based on Methylcellulose/Persian Gum Loaded With Taxifolin Enhance Bone Regeneration: An in Vitro / in Vivo Study

2021 ◽  
Author(s):  
Zahra Sadat Sajadi-Javan ◽  
Jaleh Varshosaz ◽  
Mina Mirian ◽  
Maziar Manshaei ◽  
Atousa Aminzadeh
Keyword(s):  
Animal Studies ◽  
Bone Defects ◽  
Halloysite Nanotubes ◽  
Thermosensitive Hydrogel ◽  
Alizarin Red ◽  
The Impact ◽  
Responsive Hydrogels

Abstract In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25-1.5 w/v% PG and 1-7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells.

scholarly journals Phagocytosis and Efferocytosis by Resident Macrophages in the Mouse Pancreas

2021 ◽  
Vol 12 ◽  
Author(s):  
Kristel Parv ◽  
Nestori Westerlund ◽  
Kevin Merchant ◽  
Milad Komijani ◽  
Robin S. Lindsay ◽  
...  
Keyword(s):  
Confocal Imaging ◽  
Mouse Pancreas ◽  
Tissue Microenvironment ◽  
Inflammatory State ◽  
Islet Dysfunction ◽  
Diabetes Development ◽  
The Impact

The tissue microenvironment in the mouse pancreas has been shown to promote very different polarizations of resident macrophages with islet-resident macrophages displaying an inflammatory “M1” profile and macrophages in the exocrine tissue mostly displaying an alternatively activated “M2” profile. The impact of this polarization on tissue homeostasis and diabetes development is unclear. In this study, the ability of pancreas-resident macrophages to phagocyte bacterial and endogenous debris was investigated. Mouse endocrine and exocrine tissues were separated, and tissue-resident macrophages were isolated by magnetic immunolabeling. Isolated macrophages were subjected to flow cytometry for polarization markers and qPCR for phagocytosis-related genes. Functional in vitro investigations included phagocytosis and efferocytosis assays using pH-sensitive fluorescent bacterial particles and dead fluorescent neutrophils, respectively. Intravital confocal imaging of in situ phagocytosis and efferocytosis in the pancreas was used to confirm findings in vivo. Gene expression analysis revealed no significant overall difference in expression of most phagocytosis-related genes in islet-resident vs. exocrine-resident macrophages included in the analysis. In this study, pancreas-resident macrophages were shown to differ in their ability to phagocyte bacterial and endogenous debris depending on their microenvironment. This difference in abilities may be one of the factors polarizing islet-resident macrophages to an inflammatory state since phagocytosis has been found to imprint macrophage heterogeneity. It remains unclear if this difference has any implications in the development of islet dysfunction or autoimmunity.

In Situ Gels of Acylovir Nanoemulsions For Improved Delivery to The Eye

2021 ◽  
Vol 11 ◽  
Author(s):  
Manza M. Priyanka ◽  
Shinde A. Ujwala ◽  
Sheth M. Kalyani ◽  
Namita Desai
Keyword(s):  
Animal Studies ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Corneal Stroma ◽  
Class Iii ◽  
Ophthalmic Delivery ◽  
Histopathological Studies

Background: Acyclovir, BCS Class III drug is commercially available as 3 % w/w eye ointment for multiple applications. Acyclovir nanoemulsions can be proposed to reduce dose because of improved permeation characteristics. Further, the development of in situ ophthalmic gels can be advantageous to reduce the number of applications due to increased mucoadhesion and sustaining effect. Objective: The purpose of this study was the development and evaluation of nanoemulsions based in situ gels of Acyclovir (1% w/w) as potential ophthalmic delivery systems. Methods: Nanoemulsions of Acyclovir were developed by Phase Inversion Temperature method using Capmul MCM, stearyl amine and Kolliphor RH 40 as liquid lipid, charge inducer and surfactant, respectively selected on the basis of Acyclovir solubility studies in the oil phase and emulsification ability of surfactants. These nanoemulsions were further developed into in situ ophthalmic gels using gellan gum and Methocel K4M. Results: The developed gels showed a sustained effect in vitro release studies and improved goat corneal permeation in ex vivo studies when compared to marketed ointment. HET-CAM studies concluded the absence of irritation potential, while in vivo irritation study in Wistar rats showed the absence of erythema and swelling of eyes after visual inspection for 72 hours. Histopathological studies on isolated rat corneas showed no abnormalities in anterior corneal epithelium and corneal stroma without any epithelial hyperplasia. Acyclovir nanoemulsions based in situ ophthalmic gel showed increased corneal deposition and permeation in rat eyes. Conclusion: The improved potential of developed ophthalmic gels was proven due to the reduced frequency of application compared to the marketed ointment in animal studies.

Formation of FVIIa-Antithrombin Complexes After Administration of rFVIIa to Hemophilia Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1295-1295
Author(s):  
Mirella Ezban ◽  
Erika Martin ◽  
John Christian Barrett ◽  
Janice Kuhn ◽  
Mindy Nolte ◽  
...  
Keyword(s):  
Complex Formation ◽  
Animal Studies ◽  
Factor Viia ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Rfviia Administration ◽  
The Impact ◽  
D Dimer

Abstract Abstract 1295 Poster Board I-317 Introduction Recent animal studies suggest that measurable amounts of factor VIIa and antithrombin (AT) complexes are formed and accumulate following rFVIIa administration. The in vivo rate of inhibition has been reported to be faster than the un-stimulated in vitro reaction between AT and free rFVIIa and of the same order of magnitude as the rate determined in the presence of tissue factor. To study the impact of AT inhibition on the elimination of rFVIIa in humans, we measured the pharmacokinetics (PK) of rFVIIa and rFVIIa-AT complex formation in 10 hemophilia A or B patients. Patients and Methods The PK of single-dose rFVIIa 90 μg/kg (Novo Nordisk A/S) was evaluated in 10 severe FVIII- or FIX-deficient patients in a non-bleeding state. The plasma concentrations of FVIIa activity (FVII:C), FVII antigen (FVII:Ag), FVIIa-AT, D-dimer and F1+2 fragment were determined immediately before, and at 0.5, 1, 2, 4 and 6 hours following rFVIIa dosing. Results Significant amounts of FVIIa–AT complex were formed in vivo after rFVIIa administration, and reached a maximum of 5.4 ± 0.8 nmol/L [mean ±SD] at 2 hours following rFVIIa administration and declined to 4.4 ± 0.9 nmol/L at 6 hours, as compared to 0.1 ± 0.05 nmol/L at baseline. While the FVII:C PK data in this study were consistent with previous data, there was greater total body clearance (Cltot), a larger volume of distribution (Vdss) and a shorter plasma half-life (T1/2) of FVII:C relative to FVII:Ag (Table). No change in D-dimer was observed after the administration of rFVIIa, while a slight increase in F1+2 fragment levels to 258 ± 73 pmol/L was measured 4 hours after rFVIIa dosing, as compared to 141 ± 45 pmol/L at baseline. Conclusion A significant divergence between the clearance of rFVIIa, as determined by either FVII:C or FVII:Ag measurements, can be accounted for by AT complex formation. Inhibition by AT appears thus to have a significant impact on the elimination of FVII:C activity from the circulation when rFVIIa is administered at a therapeutic dose. Similar to animal data, the formation of the FVIIa-AT complexes in vivo was faster than anticipated from in vitro studies, indicating that the exposure to the vessel wall stimulates the FVIIa inhibition by AT. Analyses of coagulation parameters did not indicate induction of systemic coagulation. Disclosures Ezban: NovoNordisk A/S: Employment. Pelzer:NovoNordisk: Employment. Agerso:NovoNordisk: Employment. Petersen:NovoNordisk: Employment. Hedner:NovoNordisk: Employment. Carr:NovoNordisk: Employment.

scholarly journals Intake of nanoparticles and impact on gut microbiota: in vitro and animal models available for testing

2021 ◽  
Vol 3 ◽  
Author(s):  
Débora Campos ◽  
Ricardo Goméz-García ◽  
Diana Oliveira ◽  
Ana Raquel Madureira
Keyword(s):  
Gut Microbiota ◽  
Oral Delivery ◽  
Animal Studies ◽  
Pathogenic Bacteria ◽  
Oral Intake ◽  
Nanosized Materials ◽  
Antimicrobial Nanoparticles ◽  
The Impact

ABSTRACT The oral delivery of compounds associated with diet or medication have an impact on the gut microbiota balance, which in turn, influences the physiologic process. Several reports have shown significant advances in clarifying the impact, interactions and outcomes of oral intake of nanoparticles and the human gut. These interactions may affect the bioavailability of the delivered compounds. In addition, there is a considerable breakthrough in the development of antimicrobial nanoparticles for intestinal pathogenic bacteria. Several in vitro fermentation and in vivo models have been developed throughout the years and were used to test these systems. The methodologies and studies carried out so far on the modulation of human and animal gut microbiome by oral delivery nanosized materials were reviewed. Overall, the available in vitro studies mimic the real physiological events enabling to select the best production conditions of nanoparticulate systems in a preliminary stage of research. On the other hand, animal studies can be used to access the dosage effect, safety and correlation between haematological, biochemical and symptoms, with gut microbiota groups and metabolites.

Effect of Thermosensitive Hydrogel Injection on Mechanical Behavior of Porcine Myocardium

2013 ◽  
Author(s):  
Bo Wang ◽  
Robbin Bertucci ◽  
Zhenqing Li ◽  
Raj Prabhu ◽  
Lakiesha Williams ◽  
...  
Keyword(s):  
Mechanical Behavior ◽  
The United States ◽  
Myocardial Infarctions ◽  
Thermosensitive Hydrogel ◽  
Thermally Responsive ◽  
Vitro Model ◽  
Biodegradable Biomaterials ◽  
Responsive Hydrogels

Myocardial infarctions (MI) afflict approximately 1.1 million individuals in the United States each year and exhibit an increasing prevalence worldwide due to the improvement of economic levels. Injection therapies for MI using biodegradable biomaterials with/without cells have been recognized to stabilize and preserve mechanical properties in the infarcted area in pre-clinical animal models. Recently, thermally responsive hydrogels, which can be injected from a syringe below 37 °C and then solidified at body temperature, are considered an attractive material for injection therapy.[1] The advantages of using an injectable hydrogel lie in its high moldability, capability of filling irregular shaped defects, and ability to be delivered to the in vivo environment by limited surgical invasion. However, it is still not very clear how the injection of thermosensitive hydrogel affects local tissue structure and mechanics. Thus, the goal of this study is to investigate possible alterations in myocardial structure and mechanical behavior after hydrogel injection using a well-controlled in vitro model.

Does Finishing and Polishing of Restorative Materials Affect Bacterial Adhesion and Biofilm Formation? A Systematic Review

2018 ◽  
Vol 43 (1) ◽  
pp. E37-E52 ◽  
Author(s):  
DAM Dutra ◽  
GKR Pereira ◽  
KZ Kantorski ◽  
LF Valandro ◽  
FB Zanatta
Keyword(s):  
Systematic Review ◽  
Bacterial Adhesion ◽  
Biofilm Formation ◽  
Surface Characteristics ◽  
Periodontal Inflammation ◽  
Restorative Materials ◽  
The Impact

SUMMARY Biofilm (bacterial plaque) accumulation on the surface of restorative materials favors the occurrence of secondary caries and periodontal inflammation. Surface characteristics of restorations can be modified by finishing and/or polishing procedures and may affect bacterial adhesion. The aim of this systematic review was to characterize how finishing and polishing methods affect the surface properties of different restorative materials with regard to bacterial adhesion and biofilm formation. Searches were carried out in MEDLINE-PubMed, EMBASE, Cochrane-CENTRAL, and LILACS databases. From 2882 potential articles found in the initial searches, only 18 met the eligible criteria and were included in this review (12 with in vitro design, four with in situ design, and two clinical trials). However, they presented high heterogeneity regarding materials considered and methodology for evaluating the desired outcome. Risk bias analysis showed that only two studies presented low risk (whereas 11 showed high and five showed medium risk). Thus, only descriptive analyses considering study design, materials, intervention (finishing/polishing), surface characteristics (roughness and surface free energy), and protocol for biofilm formation (bacterial adhesion) could be performed. Some conclusions could be drawn: the impact of roughness on bacterial adhesion seems to be related not to a roughness threshold (as previously believed) but rather to a range, the range of surface roughness among different polishing methods is wide and material dependent, finishing invariably creates a rougher surface and should always be followed by a polishing method, each dental material requires its own treatment modality to obtain and maintain as smooth a surface as possible, and in vitro designs do not seem to be powerful tools to draw relevant conclusions, so in vivo and in situ designs become strongly recommended.

scholarly journals Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity—Potential Implications for Drug Sensitivity

2020 ◽  
Vol 21 (20) ◽  
pp. 7717
Author(s):  
Kent Søe
Keyword(s):  
Side Effects ◽  
Animal Studies ◽  
Drug Sensitivity ◽  
Osteoclast Formation ◽  
Linear Process ◽  
Physiological Regulation ◽  
Complex Regulation ◽  
The Impact

Classically, osteoclast fusion consists of four basic steps: (1) attraction/migration, (2) recognition, (3) cell–cell adhesion, and (4) membrane fusion. In theory, this sounds like a straightforward simple linear process. However, it is not. Osteoclast fusion has to take place in a well-coordinated manner—something that is not simple. In vivo, the complex regulation of osteoclast formation takes place within the bone marrow—in time and space. The present review will focus on considering osteoclast fusion in the context of physiology and pathology. Special attention is given to: (1) regulation of osteoclast fusion in vivo, (2) heterogeneity of osteoclast fusion partners, (3) regulation of multi-nucleation, (4) implications for physiology and pathology, and (5) implications for drug sensitivity and side effects. The review will emphasize that more attention should be given to the human in vivo reality when interpreting the impact of in vitro and animal studies. This should be done in order to improve our understanding of human physiology and pathology, as well as to improve anti-resorptive treatment and reduce side effects.

The impact of EPA and DHA on ceramide lipotoxicity in the metabolic syndrome

2020 ◽  
pp. 1-13
Author(s):  
Chelsey Walchuk ◽  
Yidi Wang ◽  
Miyoung Suh
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Animal Studies ◽  
Sphingolipid Metabolism ◽  
Current Evidence ◽  
The Metabolic Syndrome ◽  
Epa And Dha ◽  
The Impact

Abstract The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, insulin resistance (IR) and dyslipidaemia. Consumption of a high-fat diet (HFD) enriched in SFA leads to the accumulation of ceramide (Cer), the central molecule in sphingolipid metabolism. Elevations in plasma and tissue Cer are found in obese individuals, and there is evidence to suggest that Cer lipotoxicity contributes to the MetS. EPA and DHA have shown to improve MetS parameters including IR, inflammation and hypertriacylglycerolaemia; however, whether these improvements are related to Cer is currently unknown. This review examines the potential of EPA and DHA to improve Cer lipotoxicity and MetS parameters including IR, inflammation and dyslipidaemia in vitro and in vivo. Current evidence from cell culture and animal studies indicates that EPA and DHA attenuate palmitate- or HFD-induced Cer lipotoxicity and IR, whereas evidence in humans is greatly lacking. Overall, there is intriguing potential for EPA and DHA to improve Cer lipotoxicity and related MetS parameters, but more research is warranted.

Effect of Mixing Bioactive Nanoceramics with a Thermosensitive Hydrogel as Bone Substitute

2012 ◽  
Vol 622-623 ◽  
pp. 1794-1798 ◽  
Author(s):  
Po Liang Lai ◽  
Ding Wei Hong ◽  
Carl Tsai Yu Lin ◽  
Lih Huei Chen ◽  
Wen Jer Chen ◽  
...  
Keyword(s):  
Animal Studies ◽  
Ph Value ◽  
Sol Gel ◽  
Degradation Process ◽  
Thermosensitive Hydrogel ◽  
Composite Gels ◽  
Bone Graft Substitutes ◽  
Sol Gel Transition

The composite of methoxy polyethylene glycol (mPEG) and poly(lactic-co- glycolic acid) (PLGA) thermosensitive hydrogel mixed with different mass raio of hydroxyapatite and β-tricalcium phosphate (β-TCP) were used as bone graft substitutes. The physical properties of a series of composite gels, including the critical micelle concentration (CMC), particle sizes, zeta potential, rheological behavior, morphology of composite gels, and sol–gel transition, were characterized in vitro. These composite gels could form a gel at body temperature and could be controlled easily at room temperature. During the in vitro degradation process, composite gels demonstrated a slight decrease in pH value, a slower degradation rate, less toxicity, and a higher cell survival rate. The biocompatibility of the composite gels was validated by hemolysis test. In vivo animal studies demonstrated both radiographic and gross bone union when the ratio of HAP/ β-TCP was 7:3.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

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