scholarly journals Evaluating the Physicochemical Effects of Conjugating Peptides into Thermogelling Hydrogels for Regenerative Biomaterials Applications

2021 ◽  
Author(s):  
Hannah A Pearce ◽  
Emily Y Jiang ◽  
Joseph W R Swain ◽  
Adam M Navara ◽  
Jason L Guo ◽  
...  

Abstract Thermogelling hydrogels such as poly(N-isopropyl acrylamide) (P(NiPAAm)) provide tunable constructs leveraged in many regenerative biomaterial applications. Recently, our lab developed the crosslinker poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT), which crosslinks P(NiPAAm-co-glycidyl methacrylate) via thiol-epoxy reaction and can be functionalized with azide-terminated peptides via alkyne-azide click chemistry. This study’s aim was to evaluate the impact of peptides on the physicochemical properties of the hydrogels. The physicochemical properties of the hydrogels including the lower critical solution temperature, crosslinking times, swelling, degradation, peptide release, and cytocompatibility were evaluated. The gels bearing peptides increased equilibrium swelling indicating hydrophilicity of the hydrogel components. Comparable sol fractions were found for all groups, indicating that inclusion of peptides does not impact crosslinking. Moreover, the inclusion of a matrix metalloproteinase (MMP)-sensitive peptide allowed elucidation of whether release of peptides from the network was driven by hydrolysis or enzymatic cleavage. The hydrophilicity of the network determined by the swelling behavior was demonstrated to be the most important factor in dictating hydrogel behavior over time. This study demonstrates the importance of characterizing the impact of additives on the physicochemical properties of hydrogels. These characteristics are key in determining design considerations for future in vitro and in vivo studies for tissue regeneration.

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 132-132
Author(s):  
Sergio Calsamiglia ◽  
Maria Rodriguez-Prado ◽  
Gonzalo Fernandez-Turren ◽  
Lorena Castillejos

Abstract In the last 20 years there has been extensive in vitro research on the effects of plant extracts and essential oils on rumen microbial fermentation. The main objectives have been to improve energy metabolism through a reduction in methane emissions and an increase in propionate production; and to improve protein metabolism by reducing proteolysis and deamination. While the positive results from in vitro studies has stimulated the release of commercial products based on blends of essential oils, there is limited in vivo evidence on the rumen fermentation and production performance effects. A literature search was conducted to select in vivo studies where information on rumen fermentation and animal performance was reported. For dairy cattle, we identified 37 studies of which 21 were adequate to test production performance. Ten studies reported increases and 3 decreases in milk yield. For beef cattle, we identified 20 studies with rumen fermentation profile and 22 with performance data. Average daily gain improved in 7 and decreased in 1 study. Only 1 out of 16 studies reported an improvement in feed efficiency. Data indicate that out of more than 500 products tested in vitro, only around 20 have been tested in vivo in different mixtures and doses. The use of statistical approaches will allow to describe the conditions, doses and responses in dairy and beef cattle performance. The search for postruminal effects offers another alternative use. Evidence for effects on the intestinal and systemic effects on the immune system and antioxidant status (i.e., capsicum, garlic, eugenol, cinnamaldehyde curcuma, catechins, anethol or pinene), and in the modulation of metabolic regulation (capsicum, cinnamaldehyde, curcuma or garlic) may open the opportunity for future applications. However, stability of the product in the GI tract, description of the mechanisms of action and the impact of these changes on performance needs to be further demonstrated.


2001 ◽  
Vol 45 (2) ◽  
pp. 485-494 ◽  
Author(s):  
Arnold Louie ◽  
Pamela Kaw ◽  
Partha Banerjee ◽  
Weiguo Liu ◽  
George Chen ◽  
...  

ABSTRACT In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of Candida albicans to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of C. albicans to AMB and on the outcome. The contribution of FLC-induced resistance to AMB for C. albicans also was assessed. In vitro, AMB monotherapy rapidly killed each of four C. albicans strains; FLC alone was fungistatic. Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to >40 h. Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation. Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC→AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone. This antagonistic effect persisted for at least 24 h. Simultaneous exposure of C. albicans to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of ≥1 μg/ml; antagonism was seen using an AMB concentration of 0.5 μg/ml. The in vitro findings accurately predicted outcomes in our rabbit infection model. In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB→AMB+FLC) rapidly sterilized kidneys and cardiac vegetations. AMB+FLC(simult) and FLC→AMB treatments were slower in clearing fungi from infected tissues. FLC monotherapy and FLC→AMB+FLC were both fungistatic and were the least active regimens. No adverse interaction was observed between AMB and FLC for the AMB→FLC regimen. However, FLC→AMB treatment was slower than AMB alone in clearing fungi from tissues. Thus, our in vitro and in vivo studies both demonstrate that preexposure of C. albicans to FLC reduces fungal susceptibility to AMB. The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.


2019 ◽  
Vol 20 (11) ◽  
pp. 2675 ◽  
Author(s):  
Nicholas Wilson ◽  
Robert Steadman ◽  
Ilaria Muller ◽  
Mohd Draman ◽  
D. Aled Rees ◽  
...  

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity.


2020 ◽  
Vol 22 (8) ◽  
Author(s):  
Barbara De Berardis ◽  
Magda Marchetti ◽  
Anna Risuglia ◽  
Federica Ietto ◽  
Carla Fanizza ◽  
...  

AbstractIn recent years, the introduction of innovative low-cost and large-scale processes for the synthesis of engineered nanoparticles with at least one dimension less than 100 nm has led to countless useful and extensive applications. In this context, gold nanoparticles stimulated a growing interest, due to their peculiar characteristics such as ease of synthesis, chemical stability and optical properties. This stirred the development of numerous applications especially in the biomedical field. Exposure of manufacturers and consumers to industrial products containing nanoparticles poses a potential risk to human health and the environment. Despite this, the precise mechanisms of nanomaterial toxicity have not yet been fully elucidated. It is well known that the three main routes of exposure to nanomaterials are by inhalation, ingestion and through the skin, with inhalation being the most common route of exposure to NPs in the workplace. To provide a complete picture of the impact of inhaled gold nanoparticles on human health, in this article, we review the current knowledge about the physico-chemical characteristics of this nanomaterial, in the size range of 1–100 nm, and its toxicity for pulmonary structures both in vitro and in vivo. Studies comparing the toxic effect of NPs larger than 100 nm (up to 250 nm) are also discussed.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 168 ◽  
Author(s):  
Margherita Falavigna ◽  
Paul Stein ◽  
Gøril Flaten ◽  
Massimiliano di Cagno

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.


Materials ◽  
2020 ◽  
Vol 13 (14) ◽  
pp. 3224 ◽  
Author(s):  
Beata Kaczmarek

As a phenolic acid, tannic acid can be classified into a polyphenolic group. It has been widely studied in the biomedical field of science because it presents unique antiviral as well as antibacterial properties. Tannic acid has been reported to present the activity against Influeneza A virus, Papilloma viruses, noroviruses, Herpes simplex virus type 1 and 2, and human immunodeficiency virus (HIV) as well as activity against both Gram-positive and Gram-negative bacteria as Staphylococcus aureus, Escherichia coli, Streptococcus pyogenes, Enterococcus faecalis, Pseudomonas aeruginosa, Yersinia enterocolitica, Listeria innocua. Nowadays, compounds of natural origin constitute fundaments of material science, and the trend is called “from nature to nature”. Although biopolymers have found a broad range of applications in biomedical sciences, they do not present anti-microbial activity, and their physicochemical properties are rather poor. Biopolymers, however, may be modified with organic and inorganic additives which enhance their properties. Tannic acid, like phenolic acid, is classified into a polyphenolic group and can be isolated from natural sources, e.g., a pure compound or a component of a plant extract. Numerous studies have been carried out over the application of tannic acid as an additive to biopolymer materials due to its unique properties. On the one hand, it shows antimicrobial and antiviral activity, while on the other hand, it reveals promising biological properties, i.e., enhances the cell proliferation, tissue regeneration and wound healing processes. Tannic acid is added to different biopolymers, collagen and polysaccharides as chitosan, agarose and starch. Its activity has been proven by the determination of physicochemical properties, as well as the performance of in vitro and in vivo studies. This systematics review is a summary of current studies on tannic acid properties. It presents tannic acid as an excellent natural compound which can be used to eliminate pathogenic factors as well as a revision of current studies on tannic acid composed with biopolymers and active properties of the resulting complexes.


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