scholarly journals Deterioration of Glutaraldehyde Crosslinked Heterograft Biomaterials due to Advanced Glycation End Product Formation and Serum Albumin Infiltration

2020 ◽  
Author(s):  
Christopher A. Rock ◽  
Samuel Keeney ◽  
Andrey Zakharchenko ◽  
Hajime Takano ◽  
David A. Spiegel ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Serum Albumin ◽  
Serum Protein ◽  
Heart Valves ◽  
Product Formation ◽  
Advanced Glycation ◽  
Significant Deterioration ◽  
Two Photon Microscopy ◽  
Uniaxial Testing

ABSTRACTBioprosthetic heart valves (BHV) are fabricated from glutaraldehyde cross-linked heterograft tissue, such as bovine pericardium (BP) or porcine aortic valves. BHV develop structural valve degeneration (SVD), often with calcification, requiring BHV replacement. Advanced glycation end products (AGE) are post-translational, non-enzymatic carbohydrate protein modifications. AGE are present in SVD-BHV clinical explants and not detectable in unimplanted BHV. Here, we studied the hypothesis that BHV susceptibility to AGE formation and serum protein infiltration results in deterioration of both leaflet collagen structure and mechanical properties. In vitro experiments studied BP and porcine collagen sponges (CS) for susceptibility to AGE formation using 14C-glucose and 14C-glyoxal with and without bovine serum albumin (BSA), as a model serum protein. The results showed AGE formation is a rapid and progressive process. BSA co-incubations reduced glyoxal and glucose uptake by BP and CS. Incubating BP in BSA caused a substantial increase in BP mass, enhanced by glyoxal co-incubation. Per two-photon microscopy, BP with AGE formation and BSA infiltration each induced significant disruption in collagen microarchitecture, with loss of collagen alignment and crimp. These effects are cumulative with the greatest disruption occurring when there was both AGE formation and BSA infiltration. Uniaxial testing of CS demonstrated that AGE formation, together with BSA uptake compared to controls, caused a significant deterioration in mechanical properties with a loss of viscoelastic relaxation and increased stiffness. It is concluded that AGE-BSA associated collagen structural disruption and deterioration of mechanical properties contribute to SVD.

scholarly journals Polyisobutylene-Based Thermoplastic Elastomers for Manufacturing Polymeric Heart Valve Leaflets: In Vitro and In Vivo Results

2019 ◽  
Vol 9 (22) ◽  
pp. 4773 ◽  
Author(s):  
Evgeny Ovcharenko ◽  
Maria Rezvova ◽  
Pavel Nikishau ◽  
Sergei Kostjuk ◽  
Tatiana Glushkova ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Heart Valve ◽  
Heart Valves ◽  
Reference Sample ◽  
Sample Surface ◽  
Thermoplastic Elastomers ◽  
Water Contact ◽  
Promising Alternative

Superior polymers represent a promising alternative to mechanical and biological materials commonly used for manufacturing artificial heart valves. The study is aimed at assessing poly(styrene-block-isobutylene-block-styrene) (SIBS) properties and comparing them with polytetrafluoroethylene (Gore-texTM, a reference sample). Surface topography of both materials was evaluated with scanning electron microscopy and atomic force microscopy. The mechanical properties were measured under uniaxial tension. The water contact angle was estimated to evaluate hydrophilicity/hydrophobicity of the study samples. Materials’ hemocompatibility was evaluated using cell lines (Ea.hy 926), donor blood, and in vivo. SIBS possess a regular surface relief. It is hydrophobic and has lower strength as compared to Gore-texTM (3.51 MPa vs. 13.2/23.8 MPa). SIBS and Gore-texTM have similar hemocompatibility (hemolysis, adhesion, and platelet aggregation). The subcutaneous rat implantation reports that SIBS has a lower tendency towards calcification (0.39 mg/g) compared with Gore-texTM (1.29 mg/g). SIBS is a highly hemocompatible material with a promising potential for manufacturing heart valve leaflets, but its mechanical properties require further improvements. The possible options include the reinforcement with nanofillers and introductions of new chains in its structure.

Crosslinking porcine aortic valve by radical polymerization for the preparation of BHVs with improved cytocompatibility, mild immune response, and reduced calcification

2021 ◽  
pp. 088532822098406
Author(s):  
Liangpeng Xu ◽  
Fan Yang ◽  
Yao Ge ◽  
Gaoyang Guo ◽  
Yunbing Wang
Keyword(s):  
Mechanical Properties ◽  
Immune Response ◽  
Aortic Valve ◽  
Radical Polymerization ◽  
Heart Valve ◽  
Heart Valves ◽  
Animal Experiments ◽  
Artificial Heart Valve ◽  
Valvular Stenosis

Over one million artificial heart valve transplantations are performed each year due to valvular stenosis or regurgitation. Among them, bioprosthetic heart valves (BHVs) are increasingly being used because of the absence of the need for lifelong anticoagulation. Almost all of the commercial BHVs are treated with Glutaraldehyde (GLUT). As GLUT-treated BHVs are prone to calcification and structural degradation, their durability is greatly reduced with a service life of only 12–15 years. The physiological structure and mechanical properties of the porcine aortic valve (PAV) are closer to that of a human heart valve, so in this study, PAV is used as the model to explore the comprehensive properties of the prepared BHVs by radical polymerization crosslinking method. We found that PAV treated by radical polymerization crosslinking method showed similar ECM stability and biaxial mechanical properties with GLUT-treated PAV. However, radical polymerization crosslinked PAV exhibited better cytocompatibility and endothelialization potential in vitro cell experiment as better anticalcification potential and reduced immune response than GLUT-treated PAV through subcutaneous animal experiments in rats. To conclude, a novel crosslinking method of non-glutaraldehyde fixation of xenogeneic tissues for the preparation of BHVs is expected.

scholarly journals Psoralea corylifolia L. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Cao-Sang Truong ◽  
Eunhui Seo ◽  
Hee-Sook Jun
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Hepg2 Cells ◽  
Product Formation ◽  
The Body ◽  
Psoralea Corylifolia ◽  
Advanced Glycation ◽  
Metabolic Conditions

Accumulation of advanced glycation end products (AGEs) in the body has been implicated in the pathogenesis of metabolic conditions, such as diabetes mellitus. Methylglyoxal (MGO), a major precursor of AGEs, has been reported to induce insulin resistance in both in vitro and in vivo studies. Psoralea corylifolia seeds (PCS) have been used as a traditional medicine for several diseases, but their potential application in treating insulin resistance has not yet been evaluated. This study is aimed at investigating whether PCS extract could attenuate insulin resistance induced by MGO. Male C57BL/6N mice (6 weeks old) were administered 1% MGO in their drinking water for 18 weeks, and the PCS extract (200 or 500 mg/kg) was orally administered daily from the first day of the MGO administration. We observed that both 200 and 500 mg/kg PCS extract treatment significantly improved glucose tolerance and insulin sensitivity and markedly restored p-Akt and p-IRS1/2 expression in the livers of the MGO-administered mice. Additionally, the PCS extract significantly increased the phosphorylation of Akt and IRS-1/2 and glucose uptake in MGO-treated HepG2 cells. Further studies showed that the PCS extract inhibited MGO-induced AGE formation in the HepG2 cells and in the sera of MGO-administered mice. PCS extract also increased the expression of glyoxalase 1 (GLO1) in the liver tissue of MGO-administered mice. The PCS extract significantly decreased the phosphorylation of ERK, p38, and NF-κB and suppressed the mRNA expression of proinflammatory molecules including TNF-α and IL-1β and iNOS in MGO-administered mice. Additionally, we demonstrated that the PCS extract attenuated oxidative stress, as evidenced by the reduced ROS production in the MGO-treated cells and the enhanced expression of antioxidant enzymes in the liver of MGO-administered mice. Thus, PCS extract ameliorated the MGO-induced insulin resistance in HepG2 cells and in mice by reducing oxidative stress via the inhibition of AGE formation. These findings suggest the potential of PCS extract as a candidate for the prevention and treatment of insulin resistance.

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