Evaluation of pro-angiogenic properties of an inorganic silica gel fibre fleece

2021 ◽  
Vol 30 (9) ◽  
pp. 729-736
Author(s):  
Vera Grotheer ◽  
Joachim Windolf ◽  
Christoph V Suschek

Hard-to-heal wounds represent an increasing health and economic burden on society. At present, therapy options for hard-to-heal wounds are often unsatisfactory, and the development of more effective wound treatments is urgently needed. We have shown that orthosilicic acid-releasing silica fibre fleece (SIFIB), via its pronounced anti-inflammatory properties, exhibited a significantly enhanced effect on wound closure kinetics in a porcine wound model in vivo. In this present study, we have examined in vitro the impact of the pro-angiogenic potential of SIFIB. Using an in vitro angiogenesis assay we describe for the first time how an inorganic biodegradable silica-based material significantly improved endothelial microvessel-like structure formation. We further demonstrate that the molecular mechanism of this pro-angiogenic activity of SIFIB is based on a significantly increased and tumour necrosis factor (TNF)α-dependent VEGF protein expression. In conclusion, due to its positive effects on angiogenesis, our results further indicate that decomposition products of silica-based biodegradable inorganic materials might represent very relevant therapeutic components of modern wound dressings for the treatment of hard-to-heal wounds.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ha-Rim Seo ◽  
Hyo Eun Jeong ◽  
Hyung Joon Joo ◽  
Seung-Cheol Choi ◽  
Jong-Ho Kim ◽  
...  

Background: Human body contains many kinds of different type of endothelial cells (EC). However, cellular difference of their angiogenic potential has been hardly understood. We compared in vitro angiogenic potential between arterial EC and venous EC and investigated its underlying molecular mechanisms. Method: Used human aortic endothelial cells (HAEC) which was indicated from arterial EC and human umbilical vein endothelial cells (HUVEC) indicated from venous EC. To explore angiogenic potential in detail, we adopted a novel 3D microfluidic angiogenesis assay system, which closely mimic in vivo angiogenesis. Results: In 3D microfluidic angiogenesis assay system, HAEC demonstrated stronger angiogenic potential compared to HUVEC. HAEC maintained its profound angiogenic property under different biophysical conditions. In mRNA microarray sorted on up- regulated or down-regulated genes, HAEC demonstrated significantly higher expression of gastrulation brain homeobox 2 (GBX2), fibroblast grow factor 2 (FGF2), FGF5 and collagen 8a1. Angiogenesis-related protein assay revealed that HAEC has higher secretion of endogenous FGF2 than HUVEC. HAEC has only up-regulated FGF2 and FGF5 in this part of FGF family. Furthermore, FGF5 expression under vascular endothelial growth factor-A (VEGF-A) stimulation was higher in HAEC compared to HUVEC although VEGF-A augmented FGF5 expression in both HAEC and HUVEC. Those data suggested that FGF5 expression in both HAEC and HUVEC is partially dependent to VEGF-A stimulate. HUVEC and HAEC reduced vascular density after FGF2 and FGF5 siRNA treat. Conclusion: HAEC has stronger angiogenic potential than HUVEC through up-regulation of endogenous FGF2 and FGF5 expression


2020 ◽  
Vol 11 ◽  
pp. 204173142094933 ◽  
Author(s):  
Hye Sung Kim ◽  
Junyu Chen ◽  
Lin-Ping Wu ◽  
Jihua Wu ◽  
Hua Xiang ◽  
...  

To reduce excessive scarring in wound healing, electrospun nanofibrous meshes, composed of haloarchaea-produced biodegradable elastomer poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV), are fabricated for use as a wound dressing. Three PHBV polymers with different 3HV content are used to prepare either solution-cast films or electrospun nanofibrous meshes. As 3HV content increases, the crystallinity decreases and the scaffolds become more elastic. The nanofibrous meshes exhibit greater elasticity and elongation at break than films. When used to culture human dermal fibroblasts in vitro, PHBV meshes give better cell attachment and proliferation, less differentiation to myofibroblasts, and less substrate contraction. In a full-thickness mouse wound model, treatment with films or meshes enables regeneration of pale thin tissues without scabs, dehydration, or tubercular scar formation. The epidermis of wounds treated with meshes develop small invaginations in the dermis within 2 weeks, indicating hair follicle and sweat gland regeneration. Consistent with the in vitro results, meshes reduce myofibroblast differentiation in vivo through downregulation of α-SMA and TGF-β1, and upregulation of TGF-β3. The regenerated wounds treated with meshes are softer and more elastic than those treated with films. These results demonstrate that electrospun nanofibrous PHBV meshes mitigate excessive scar formation by regulating myofibroblast formation, showing their promise for use as wound dressings.


Author(s):  
Agata Ładniak

<p>Skin injuries are a health problem and can lead to serious, significant deterioration in the quality of life and, consequently, even illness and disability. Therefore, after wounding, immediate regeneration of the tissue is necessary to avoid further complications and pathogenesis. Consequently, many wound healing strategies have been developed, leading to the progress in constructing of multifunctional tissue substitutes for the skin, biomembranes, scaffolds and intelligent dressings. The field of science focusing on the creation of the above-mentioned products is tissue engineering (TE). Its main goal is to find a system that is able to replace or be a model that perfectly mimics the form and function of the skin. Research carried out on such constructs is mainly based on the analysis of mechanical properties (porosity, elasticity), as well as the assessment of the impact of individual components on processes related to the formation of new tissue as cell proliferation and differentiation, proliferation, angiogenesis - through <em>in vivo</em> studies (using animal models: mice, New Zealand rabbits) and <em>in vitro</em> (most often using mouse fibroblasts - L929). Skin constructions may have potential applications as wound dressings or skin substitutes in cases of severe skin damage.</p>


2019 ◽  
Vol 3 (s1) ◽  
pp. 109-109
Author(s):  
Drew Goldberg ◽  
Ann Gaffey ◽  
Minna Chen ◽  
Elizabeth Li ◽  
Samuel Kim ◽  
...  

OBJECTIVES/SPECIFIC AIMS: The primary aim is to assess differences in therapeutic effect between MSC and EPC EVs on acute ischemic rat hearts through delivery in a biocompatible and shear-thinning hydrogel. Primary outcomes for therapeutic assessment include an in-vitro angiogenesis assay and in-vivo hemodynamic analysis, mainly identifying differences in ejection fraction and contractility. Secondary hemodynamic outcomes include cardiac output, stroke volume, and end-diastolic pressure volume relationship (EDPVR). Secondary structural outcomes include post-mortem scar analysis and immunohistochemistry (IHC) staining for angiomyogenesis. METHODS/STUDY POPULATION: MSCs and EPCs will be cultured according to previously published protocols. EVs will be isolated from cultured cell lines through precipitation methods with polyethylene glycol. EVs will be qualitatively analyzed with nanoparticle tracking analysis (NTA) and flow cytometry. The shear thinning hydrogel (STG) will be constructed using a hyaluronic backbone conjugated to adamantane or beta-cyclodextrin, ultimately facilitating guest-host interactions with shear thinning properties. Controls and treatment groups mixed with the hydrogel will be injected into the border zone of infarcted Wistar rat hearts immediately following a left anterior descending artery ligation. Hemodynamic assessment will be performed at four weeks through left ventricular catheter based pressure-volume recordings. Ex-vivo analysis will include scar thickness assessment using Masson collagen staining and IHC stain for vessel (anti-vonWillebrand factor; anti-Isolectin) and myocyte formation (anti-cardiac Troponin I). RESULTS/ANTICIPATED RESULTS: We hypothesize that, in-vitro, MSC-EVs will demonstrate non-inferior angiogenic potential as compared to EPC-EVs. We posit that MSC-EVs will demonstrate superior therapeutic effect to EPC-EVs in-vivo as measured by functional hemodynamics and structural assessment. We have successfully isolated MSC and EPC EVs and have validated uniformity across EV populations (Figure 1). Preliminary data from the angiogenesis assay (n=3) demonstrated that MSC-EV and EPC-EV produce non-significantly different angiogenic potential as measured by number of vascular meshing extremes (p=0.144) and length of master vascular segment (p=0.193), with significant differences compared to either positive or negative controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Novel regenerative therapies are needed for patients with a history of AMI given current limitations to therapy and sequelae of ischemic heart disease. Delivery of extracellular vesicles through a shear-thinning gel is a novel “off-the-shelf” translational approach to address the current clinical need.


2007 ◽  
Vol 292 (3) ◽  
pp. E891-E899 ◽  
Author(s):  
Raul M. Luque ◽  
Zhi H. Huang ◽  
Bhumik Shah ◽  
Theodore Mazzone ◽  
Rhonda D. Kineman

Leptin-deficient obese mice ( ob/ob) have decreased circulating growth hormone (GH) and pituitary GH and ghrelin receptor (GHS-R) mRNA levels, whereas hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST) expression do not differ from lean controls. Given the fact that GH is suppressed in diet-induced obesity (a state of hyperleptinemia), it remains to be determined whether the absence of leptin contributes to changes in the GH axis of ob/ob mice. Therefore, to study the impact of leptin replacement on the hypothalamic-pituitary GH axis of ob/ob mice, leptin was infused for 7 days (sc), resulting in circulating leptin levels that were similar to wild-type controls (∼1 ng/ml). Leptin treatment reduced food intake, body weight, and circulating insulin while elevating circulating n-octanoyl ghrelin concentrations. Leptin treatment did not alter hypothalamic GHRH, SST, or GHS-R mRNA levels compared with vehicle-treated controls. However, leptin significantly increased pituitary GH and GHRH-R expression and tended to enhance circulating GH levels, but this latter effect did not reach statistical significance. In vitro, leptin (1 ng/ml, 24 h) did not affect pituitary GH, GHRH-R, or GHS-R mRNA but did enhance GH release. The in vivo effects of leptin on circulating hormone and pituitary mRNA levels were not replicated by pair feeding ob/ob mice to match the food intake of leptin-treated mice. However, leptin did prevent the fall in hypothalamic GHRH mRNA and circulating IGF-I levels observed in pair-fed mice. These results demonstrate that leptin replacement has positive effects on multiple levels of GH axis function in ob/ob mice.


2020 ◽  
pp. 002203452096478
Author(s):  
H.T. Dos Santos ◽  
K. Nam ◽  
C.T. Brown ◽  
S.M. Dean ◽  
S. Lewis ◽  
...  

New strategies for tissue engineering have great potential for restoring and revitalizing impaired tissues and organs, including the use of smart hydrogels that can be modified to enhance organization and functionality of the salivary glands. For instance, monomers of laminin-111 peptides chemically conjugated to fibrin hydrogel (L1pM-FH) promote cell cluster formation in vitro and salivary gland regeneration in vivo when compared with fibrin hydrogel (FH) alone; however, L1pM-FH produce only weak expression of acinar differentiation markers in vivo (e.g., aquaporin-5 and transmembrane protein 16). Since previous studies demonstrated that a greater impact can be achieved when trimeric forms were used as compared with monomeric or dimeric forms, we investigated the extent to which trimers of laminin-111 chemically conjugated to FH (L1pT-FH) can increase the expression of acinar differentiation markers and elevate saliva secretion. In vitro studies using Par-C10 acinar cells demonstrated that when compared with L1pM-FH, L1pT-FH induced similar levels of acinar-like cell clustering, polarization, lumen formation, and calcium signaling. To assess the performance of the trimeric complex in vivo, we compared the ability of L1pM-FH and L1pT-FH to increase acinar differentiation markers and restore saliva flow rate in a salivary gland wound model of C57BL/6 mice. Our results show that L1pT-FH applied to wounded mice significantly improved the expression of the acinar differentiation markers and saliva secretion when compared with the monomeric form. Together, these positive effects of L1pT-FH warrant its future testing in additional models of hyposalivation with the ultimate goal of applying this technology in humans.


HortScience ◽  
2019 ◽  
Vol 54 (12) ◽  
pp. 2188-2194
Author(s):  
Javiera Morales ◽  
Ximena Besoain ◽  
Italo F. Cuneo ◽  
Alejandra Larach ◽  
Laureano Alvarado ◽  
...  

Excessive nitrogen (N) use in agriculture has been associated with increased severity of the damage caused by Phytophthora species. In this study, we investigated the impact in vitro and in vivo of N about Phytophthora cinnamomi. The preliminary in vitro assay showed the effect of different N sources on the mycelial growth of P. cinnamomi. This assay indicated that ammonium nitrate (NH4NO3) and ammonium sulfate [(NH4)2SO4] allowed for greater control of P. cinnamomi mycelia in comparison with calcium nitrate [Ca(NO3)2] and potassium nitrate (KNO3) when used with 1000 ppm N. The in vivo assay showed the severity of P. cinnamomi in 5-month-old Juglans regia saplings grown under greenhouse conditions. We selected NH4NH3 as the source for N for the greenhouse assay, considering the inhibitory effect on the ingrowth of P. cinnamomi and the intensive use of this fertilizer in agriculture. Walnut saplings were fertilized with 0, 35, 70, 140, 210, and 1050 ppm N and were inoculated with zoospores of P. cinnamomi 45 d after the application of nitrogen treatment (DAA). They were harvested at 90 DAA. We found that a 70-ppm N fertilization reduced the development of P. cinnamomi, resulting in lower root and canopy damage indices (DIs) than the unfertilized inoculated treatments and fertilized treatments greater than 140 ppm. The results of the in vitro and in vivo assay agree that increased N concentrations were associated with reduced mycelium growth of P. cinnamomi, providing further evidence that N fertilization can mitigate this disease. Greater root and canopy damage was observed in saplings fertilized with 1050 ppm N, regardless of whether they were inoculated with P. cinnamomi, as a result of N phytotoxicity (verified through foliar analysis). In contrast, inoculated and unfertilized saplings (N0) also showed high root and canopy DIs associated either with the inoculation with P. cinnamomi or the no fertilization treatment. We postulate that 70 ppm N is the best fertilization rate for J. regia saplings because the positive effects of N on growth are maximized and the damage caused by P. cinnamomi is mitigated.


2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.


2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali

2019 ◽  
Vol 33 (9) ◽  
pp. 1285-1297 ◽  
Author(s):  
Cornelia Wiegand ◽  
Martin Abel ◽  
Uta-Christina Hipler ◽  
Peter Elsner ◽  
Michael Zieger ◽  
...  

Background Application of controlled in vitro techniques can be used as a screening tool for the development of new hemostatic agents allowing quantitative assessment of overall hemostatic potential. Materials and methods Several tests were selected to evaluate the efficacy of cotton gauze, collagen, and oxidized regenerated cellulose for enhancing blood clotting, coagulation, and platelet activation. Results Visual inspection of dressings after blood contact proved the formation of blood clots. Scanning electron microscopy demonstrated the adsorption of blood cells and plasma proteins. Significantly enhanced blood clot formation was observed for collagen together with β-thromboglobulin increase and platelet count reduction. Oxidized regenerated cellulose demonstrated slower clotting rates not yielding any thrombin generation; yet, led to significantly increased thrombin-anti-thrombin-III complex levels compared to the other dressings. As hemostyptica ought to function without triggering any adverse events, induction of hemolysis, instigation of inflammatory reactions, and initiation of the innate complement system were also tested. Here, cotton gauze provoked high PMN elastase and elevated SC5b-9 concentrations. Conclusions A range of tests for desired and undesired effects of materials need to be combined to gain some degree of predictability of the in vivo situation. Collagen-based dressings demonstrated the highest hemostyptic properties with lowest adverse reactions whereas gauze did not induce high coagulation activation but rather activated leukocytes and complement.


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