In vitro Degradation Analysis of 3D-architectured Gelatin-based Hydrogels

MRS Advances ◽  
2019 ◽  
Vol 5 (12-13) ◽  
pp. 633-642
Author(s):  
Jun Hon Pang ◽  
Christian Wischke ◽  
Andreas Lendlein

ABSTRACT:Multifunctional biopolymer-based materials are promising candidates for next generation regenerative biomaterials. Understanding the degradation behavior of biomaterials is vital for ensuring biological safety, as well as for better control of degradation properties based on rational design of a material’s physical and chemical characteristics. In this study, we decipher the degradation of a hydrogel prepared from gelatin and lysine diisocyanate ethyl ester (LDI) using in vitro models, which simulate hydrolytic, oxidative and enzymatic degradation (collagenase). Gravimetrical, morphological, mechanical and chemical properties were evaluated. Notably, the hydrogels were relatively resistant to hydrolytic degradation, but degraded rapidly within 21 days (>95% mass loss) under oxidative and collagenase degradation. Oxidative and collagenase degradation rapidly decreased the storage and loss modulus of the hydrogels, and slightly increased their viscous component (tan δ). For each degradation condition, the results suggest different possible degradation pathways associated to the gelatin polypeptide backbone, urea linkages and ester groups. The primary degradation mechanisms for the investigated gelatin based hydrogels are oxidative and enzymatic in nature. The relative hydrolytic stability of the hydrogels should ensure minimal degradation during storage and handling prior to application in surgical theatres.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yanwen Chen ◽  
Travis B. Lear ◽  
John W. Evankovich ◽  
Mads B. Larsen ◽  
Bo Lin ◽  
...  

AbstractSARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.


Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2998
Author(s):  
Mohammed Nadeem Bijle ◽  
Manikandan Ekambaram ◽  
Edward Lo ◽  
Cynthia Yiu

The in vitro study objectives were to investigate the effect of arginine (Arg) incorporation in a 5% sodium fluoride (NaF) varnish on its physical and chemical properties including F/Arg release. Six experimental formulations were prepared with L-arginine (L-Arg) and L-arginine monohydrochloride at 2%, 4%, and 8% w/v in a 5% NaF varnish, which served as a control. The varnishes were subjected to assessments for adhesion, viscosity, and NaF extraction. Molecular dynamics were simulated to identify post-dynamics total energy for NaF=Arg/Arg>NaF/Arg<NaF concentrations. The Arg/F varnish release profiles were determined in polyacrylic lactate buffer (pH-4.5; 7 days) and artificial saliva (pH-7; 1 h, 24 h, and 12 weeks). Incorporation of L-Arg in NaF varnish significantly influences physical properties ameliorating retention (p < 0.001). L-Arg in NaF varnish institutes the Arg-F complex. Molecular dynamics suggests that NaF>Arg concentration denotes the stabilized environment compared to NaF<Arg (p < 0.001). The 2% Arg-NaF exhibits periodic perennial Arg/F release and shows significantly higher integrated mean F release than NaF (p < 0.001). Incorporating 2% L-arginine in 5% NaF varnish improves its physical properties and renders a stable matrix with enduring higher F/Arg release than control.


Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5722
Author(s):  
Yijie Lou ◽  
Kaxi Yu ◽  
Xiajun Wu ◽  
Zhaojun Wang ◽  
Yusheng Cui ◽  
...  

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Edward B Neufeld ◽  
Alice Ossoli ◽  
Seth G Thacker ◽  
Boris Vaisman ◽  
Milton Pryor ◽  
...  

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, and chemical properties, to wild-type and Lcat -/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat -/- mice, which have low HDL but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat -/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes, where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA 2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat -/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of LCAT induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.


2019 ◽  
Vol 391 ◽  
pp. 215-220 ◽  
Author(s):  
Andrey N. Dmitriev ◽  
R.V. Petukhov ◽  
G.Yu. Vitkina ◽  
E.A. Vyaznikova

Questions regarding the oxidizing roasting of raw iron ore materials (agglomerate and pellets) are studied. Features of the phase structure of raw iron ore materials containing titanium and vanadium are discussed. Reducibility, durability, and temperatures of the softening and melting of metallurgical raw iron ore materials are studied in vitro. Object of research – titaniferous ores with various titanium dioxide content. The behavior of agglomerate and pellets in a blast furnace are studied, as well as the influence of their physical and chemical properties on heat and mass transfer processes using a mathematical model of the blast furnace process [1].


10.12737/2753 ◽  
2013 ◽  
Vol 20 (4) ◽  
pp. 160-165
Author(s):  
Сергиевич ◽  
A. Sergievich ◽  
Чайка ◽  
Vladimir Chayka ◽  
Голохваст ◽  
...  

There are both in the domestic and the world science a discussion about the biological activity of water-insoluble solid microparticles technogenous and natural. These interactions are studied in the context of the professional pathology, hygiene and nanotoxicology. The purpose of this research was to study the mechanisms of action of particles of natural minerals of various sizes on biological systems. The paper is based on the applied modern methods which allow to determine the degree of interaction of microelements with the functional systems of the organism. Analysis of the results showed that the application of these methods has a number of shortcomings in the experiments in vivo and in vitro, associated with the physical and chemical features of zeolites. It is established that under cultivation in 6- and 24-hole tablets, the zeolite in a dose of 50 mg/ml covers all the cells attached to the glass. In the fields of view of the cells are practically invisible. Thus, an assessment of toxic effects or functional condition of the cells is not possible. Zeolite being water-insoluble compound wich is not subjected to the pipetting. At the delete zeolite of culture, there is practically full elimination of cells from the hole. Accumulation of the primary information about the biological effects of nano - and microparticles is extremely important. This allows the authors to make some conclusions, but the decision of a question on the mechanism of biological activity, especially the prediction of some properties of particles without the study of physical-chemical properties of the particles isn&#180;t possible.


2015 ◽  
Vol 66 (2) ◽  
pp. 97-108 ◽  
Author(s):  
Veno Kononenko ◽  
Mojca Narat ◽  
Damjana Drobne

Abstract When nanoparticles enter the body, their interactions with cells are almost unavoidable. Unintended nanoparticle interaction with immune cells may elicit a molecular response that can have toxic effects and lead to greater susceptibility to infectious diseases, autoimmune disorders, and cancer development. As evidenced by several studies, nanoparticle interactions with biological systems can stimulate inflammatory or allergic reactions and activate the complement system. Nanoparticles can also stimulate immune response by acting as adjuvants or as haptens. Immunosuppressive effects have also been reported. This article gives a brief review of in vitro and in vivo research evidencing stimulatory or suppressive effects of nanoparticles on the immune system of mammals. In order to ensure safe use of nanosized particles, future research should focus on how their physical and chemical properties influence their behaviour in the biological environment, as they not only greatly affect nanoparticle-immune system interactions but can also interfere with experimental assays


Author(s):  
Loredana Stabili ◽  
Roberto Schirosi ◽  
Angela Di Benedetto ◽  
Alessandro Merendino ◽  
Luciano Villanova ◽  
...  

Although mucus plays many different roles among marine invertebrates, relatively little is known about the link between biochemical structure and function. In the present study we focused on some physical and chemical properties of the polychaeteSabella spallanzanii's mucus such as viscosity, osmolarity, electrical conductivity, elemental composition, the protein and carbohydrate content, the total lipids and fatty acid composition, and polychlorinated biphenyls (PCBs) contamination. Moreover, an antimicrobial activity of the mucus was investigated. The water content ofS. spallanzaniimucus was 96.2±0.3%. By dry weight 26±1.2% was protein, 8±0.21% was carbohydrate and only 0.1% lipid, much of the remainder of the dry weight was inorganic (about 65.2%). The estimated PCBs content was <0.005 μg g−1. The mucus ofS. spallanzaniiexerted a natural lysozyme-like activity and producedin vitrothe growth inhibition ofVibrio anguillarum, Vibrio harveyi, Pseudomonas aeruginosaandCandida albicans.The findings from this study contribute to improve the limited knowledge available on the mucus composition in invertebrates and have implications for future investigations related to employment ofS. spallanzaniimucus as a source of compounds of pharmaceutical and marine technological interest.


Blood ◽  
1965 ◽  
Vol 26 (5) ◽  
pp. 521-532 ◽  
Author(s):  
WILLIAM E. HATHAWAY ◽  
LORETTA P. BELHASEN ◽  
HELEN S. HATHAWAY

Abstract Studies of defective plasma thromboplastin formation in four siblings indicated a defect which was different from any of the known coagulation factor deficiency states. Although none of the children had any history of hemorrhagic tendencies, a prolonged whole blood clotting time in an 11-year-old girl led to the findings of a markedly prolonged partial thromboplastin time (PTT), abnormal thromboplastin generation test (TGT), and a normal prothrombin time in the patient and in three of her ten siblings. The abnormal PTT and TGT were corrected by aluminum hydroxide adsorbed fresh plasma and by serum. Using the kaolin-PTT system, equal mixtures of plasma from the patients and normal plasma produced a normal time. In addition, plasmas deficient in plasma thromboplastin antecedent (PTA), Hageman factor (HF), antihemophilic factor (AHF), or plasma thromboplastin component (PTC) corrected the abnormality. Physical and chemical properties of plasma correcting the defect in vitro indicated that the defect is closely related to that found in PTA and HF deficient plasma.


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