scholarly journals A Radiation-Crosslinked Gelatin Hydrogel That Promotes Tissue Incorporation of an Expanded Polytetrafluoroethylene Vascular Graft in Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1105
Author(s):  
Sohei Matsuura ◽  
Toshio Takayama ◽  
Tomoko G. Oyama ◽  
Kotaro Oyama ◽  
Mitsumasa Taguchi ◽  
...  

A prosthetic vascular graft that induces perigraft tissue incorporation may effectively prevent serious sequelae such as seroma formation and infection. Radiation-crosslinked gelatin hydrogel (RXgel) mimics the chemical and physical properties of the in vivo extracellular matrix and may facilitate wound healing by promoting tissue organization. Fibroblasts cultured on RXgel actively migrated into the gel for up to 7 days. RXgels of three different degrees of hardness (Rx[10], soft; Rx[15], middle; Rx[20], hard) were prepared, and small disc-like samples of RXgels were implanted into rats. In vitro and in vivo results indicated that Rx[10] was too soft to coat vascular grafts. Thus, expanded polytetrafluoroethylene (ePTFE) vascular grafts coated with RXgel were developed using Rx[15] and Rx[20] gels, and ring-shaped slices of the graft were implanted into rats. Alpha-smooth muscle actin (SMA) and type III collagen (Col-III) levels were detected by immunohistochemistry. Immunohistochemical staining for SMA and Col-III demonstrated that RXgel-coated vascular grafts induced more granulation tissue than non-coated grafts on days 14 and 28 after implantation. RXgel-coated ePTFE vascular grafts may provide a solution for patients by reducing poor perigraft tissue incorporation.

2020 ◽  
Author(s):  
Shunji Kurokawa ◽  
Yoshihide Hashimoto ◽  
Seiichi Funamoto ◽  
Akitatsu Yamashita ◽  
Kazuhiro Yamazaki ◽  
...  

ABSTRACTAutologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals potentially substitute for autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM) which would be feasible for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries then evaluated graft patency, ECM preservation and recellularization. Surgical procedure not to damage luminal surface of the grafts from drying significantly increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. Luminal surface of grafts was thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy on luminal surface of implanted grafts exhibited cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells.


PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254160
Author(s):  
Shunji Kurokawa ◽  
Yoshihide Hashimoto ◽  
Seiichi Funamoto ◽  
Kozue Murata ◽  
Akitatsu Yamashita ◽  
...  

Autologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals can potentially be a substitute of autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM), creating feasible conditions for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries and posteriorly evaluated graft patency, ECM preservation and recellularization. Avoiding damage of the luminal surface of the grafts from drying significantly during the surgical procedure increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed, even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. The luminal surface of the grafts were thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy of the luminal surface of implanted grafts exhibited a cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of the tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells.


Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nozomi Igarashi ◽  
Megumi Honjo ◽  
Makoto Aihara

AbstractWe examined the effects of mTOR inhibitors on the fibrotic response induced by transforming growth factor-beta2 (TGF-β2) in cultured human trabecular meshwork (hTM) cells. TGF-β2-induced expression of fibronectin, collagen type I, alpha 1 chain (COL1A1), and alpha-smooth muscle actin (αSMA) in hTM cells was examined in the presence or absence of mTOR inhibitors using quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The migration rates of hTM cells were examined in the presence of TGF-β2 with or without mTOR inhibitors. An in vitro study showed that the expression of fibronectin, COL1A1, and αSMA was upregulated by TGF-β2 treatment of hTM cells; such upregulation was significantly suppressed by mTOR inhibitors. The inhibitors significantly reduced the migration rate of TGF-β2-stimulated hTM cells. mTOR inhibitors may usefully reduce the fibrotic response of hTM cells and we may have to explore if it is also effective in in vivo model.


2019 ◽  
Vol 39 (10) ◽  
pp. 2168-2191 ◽  
Author(s):  
Bronson A. Haynes ◽  
Li Fang Yang ◽  
Ryan W. Huyck ◽  
Eric J. Lehrer ◽  
Joshua M. Turner ◽  
...  

Objective: Endothelial cells (EC) in obese adipose tissue (AT) are exposed to a chronic proinflammatory environment that may induce a mesenchymal-like phenotype and altered function. The objective of this study was to establish whether endothelial-to-mesenchymal transition (EndoMT) is present in human AT in obesity and to investigate the effect of such transition on endothelial function and the endothelial particulate secretome represented by extracellular vesicles (EV). Approach and Results: We identified EndoMT in obese human AT depots by immunohistochemical co-localization of CD31 or vWF and α-SMA (alpha-smooth muscle actin). We showed that AT EC exposed in vitro to TGF-β (tumor growth factor-β), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers. The phenotypic change results in failure to maintain a tight barrier in culture, increased migration, and reduced angiogenesis. EndoMT also reduced mitochondrial oxidative phosphorylation and glycolytic capacity of EC. EVs produced by EC that underwent EndoMT dramatically reduced angiogenic capacity of the recipient naïve ECs without affecting their migration or proliferation. Proteomic analysis of EV produced by EC in the proinflammatory conditions showed presence of several pro-inflammatory and immune proteins along with an enrichment in angiogenic receptors. Conclusions: We demonstrated the presence of EndoMT in human AT in obesity. EndoMT in vitro resulted in production of EV that transferred some of the functional and metabolic features to recipient naïve EC. This result suggests that functional and molecular features of EC that underwent EndoMT in vivo can be disseminated in a paracrine or endocrine fashion and may induce endothelial dysfunction in distant vascular beds.


2008 ◽  
Vol 22 (S2) ◽  
pp. 605-605
Author(s):  
Mauricio Antonio Contreras ◽  
Mathew Douglas Phaneuf ◽  
Shengqian Wu ◽  
Martin J. Bide ◽  
Frank W. LoGerfo

2016 ◽  
Vol 63 (6) ◽  
pp. 1620-1630.e4 ◽  
Author(s):  
Jennifer M. Bastijanic ◽  
Roger E. Marchant ◽  
Faina Kligman ◽  
Matthew T. Allemang ◽  
Ryan O. Lakin ◽  
...  

2019 ◽  
Author(s):  
Santoshi Muppala ◽  
Mohammed Tanjimur Rahman ◽  
Irene Krukovets ◽  
Dmitriy Verbovetskiy ◽  
Elzbieta Pluskota ◽  
...  

AbstractAimsThrombopspondin-4 (TSP4) is a pro-angiogenic protein that has been implicated in tissue remodeling and local vascular inflammation. TSP4 and, in particular, its SNP variant, P387 TSP4, have been associated with cardiovascular disease.Macrophages are central to initiation and resolution of inflammation and development of atherosclerotic lesions, but the effects of the P387 TSP4 on macrophages remain essentially unknown. We examined the effects of the P387 TSP4 variant on macrophages in cell culture andin vivoin a murine model of atherosclerosis. Further, the levels and distributions of the twoTSP4 variants were assessed in human atherosclerotic arteries.Methods and ResultsInApoE−/−/P387-TSP4 knock-in mice, atherosclerotic lesions accumulated more macrophages than lesions bearing A387 TSP4. The levels of inflammatory markers were increased in lesions ofApoE−/−/P387-TSP4 knock-in mice compared toApoE−/−mice. Lesions in human arteries from individuals carrying the P387 variant had higher levels of TSP4 and higher macrophage accumulation. P387 TSP4 was more active in supporting adhesion of cultured human and mouse macrophages in experiments using recombinant TSP4 variants and in cells derived from P387-TSP4 knock-in mice.ConclusionsTSP4 supports the adhesion of macrophages and their accumulation in atherosclerotic lesions. P387 TSP4 is more active in supporting these pro-inflammatory events in the vascular wall, which may contribute to the increased association of P387 TSP4 with cardiovascular disease.AbbreviationsBSA, bovine serum albumin; DMSO, dimethyl sulfoxide; ECM, extracellular matrix;Thbs4−/−, thrombospondin-4 gene knock-out; WT, wild type; P387-TSP4 KI, P387TSP4knock-in mice; OCT, Optimum Cutting Temperature; vWF, von Willebrand factor; α-SMA, alpha-smooth muscle actin; Egr2, Early Growth Response 2; PBS, Phosphate Buffer saline; DMEM, Dulbecco’s Modified Eagle Medium.


Author(s):  
Zheng Xing ◽  
Shuting Wu ◽  
Chen Zhao ◽  
Yating Bai ◽  
Dawei Jin ◽  
...  

Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular graft is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular...


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