Antimineralization treatments for bioprosthetic heart valves

Schoen, Frederick J.; Levy, Robert J.; Hilbert, Stephen L.; Bianco, Richard W.

doi:10.1016/s0022-5223(19)34619-7

Cited by 57 publications

(17 citation statements)

References 20 publications

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“…Calcification is the most frequent cause of the clinical failure of bioprosthetic heart valve (BPHV) replacements fabricated from porcine aortic valves crosslinked with glutaraldehyde. 1 Calcification refers to the deposition of calcium phosphates and associated minerals in the BPHV tissues. This calcific degeneration is usually followed by stenosis or cuspal tearing with regurgitation, and can result in prosthesis failure.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of aortic wall calcification in bioprosthetic heart valves by ethanol pretreatment: Biochemical and biophysical mechanisms

Lee

Vyavahare

Zand

et al. 1998

J. Biomed. Mater. Res.

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The effectiveness of ethanol pretreatment on preventing calcification of glutaraldehyde-fixed porcine aortic bioprosthetic heart valve (BPHV) cusps was previously demonstrated, and the mechanism of action of ethanol was attributed in part to both lipid removal and a specific collagen conformational change. In the present work, the effect of ethanol pretreatment on BPHV aortic wall calcification was investigated using both rat subdermal and sheep circulatory implants. Ethanol pretreatment significantly inhibited calcification of BPHV aortic wall, but with less than complete inhibition. The maximum inhibition of calcification of BPHV aortic wall was achieved using an 80% ethanol pretreatment; calcium levels were 71.80+/-8.45 microg/mg with 80% ethanol pretreatment compared to the control calcium level of 129.90+/-7.24 microg/mg (p = 0.001). Increasing the duration of ethanol exposure did not significantly improve the inhibitory effect of ethanol on aortic wall calcification. In the sheep circulatory implants, ethanol pretreatment partly prevented BPHV aortic wall calcification with a calcium level of 28.02+/-4.42 microg/mg compared to the control calcium level of 56.35+/-6.14 microg/mg (p = 0.004). Infrared spectroscopy (ATR-FTIR) studies of ethanol-pretreated BPHV aortic wall (vs. control) demonstrated a significant change in protein structure due to ethanol pretreatment. The water content of the aortic wall tissue and the spin-lattice relaxation times (T1) as assessed by proton nuclear magnetic resonance spectroscopy did not change significantly owing to ethanol pretreatment. The optimum condition of 80% ethanol pretreatment almost completely extracted both phospholipids and cholesterol from the aortic wall; despite this, significant calcification occurred. In conclusion, these results clearly demonstrate that ethanol pretreatment is significantly but only partially effective for inhibition of calcification of BPHV aortic wall and this effect may be due in part to lipid extraction and protein structure changes caused by ethanol. It is hypothesized that ethanol pretreatment may be of benefit for preventing bioprosthetic aortic wall calcification only in synergistic combination with another agent.

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Section: Introductionmentioning

confidence: 99%

Inhibition of aortic wall calcification in bioprosthetic heart valves by ethanol pretreatment: Biochemical and biophysical mechanisms

Lee

Vyavahare

Zand

et al. 1998

J. Biomed. Mater. Res.

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“…Calcification is one of the problems encountered with implantable biomaterials which is influenced by the structure of the implantable system and determines its in-vivo therapeutic efficiency and clinical fate [45]. Calcification of tissue or systems mainly depends upon chemical factors that can operate at the cellular level around different tissues or biomaterials [46].…”

Section: Ipn Film As a Calcifiable Matrix Systemmentioning

confidence: 99%

Pharmaceutical and Biomedical Applications of Interpenetrating Polymer Network

Jain¹,

Sharma²,

Banik³

et al. 2011

CDTH

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Interpenetrating polymer network (IPN) based drug delivery system is basically designed to deliver drugs at a predetermined rate for a desired period of time with minimum fluctuation. Due to its physical and biological characteristics such as enhanced solubility of hydrophobic drugs, excellent swelling capacity, imparting drug stability in the formulations, biodegradability, biocompatibility, weak antigenecity and targeting of drug in a specific tissue make it suitable for drug delivery as well as biomedical applications. IPN based drug delivery is primarily used for controlled release of drugs. These systems are also used for tissue engineering such as cartilage scaffolds, bone substitutes etc. The purpose of this review article is to cover recent advances on IPN based on its utilization as drug delivery matrix system for pharmaceutical applications as well as in tissue engineering for biomedical applications. Consequently, IPN is regarded as one of the most valuable novel biomaterials.

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“…The clinical usage of bioprosthetic heart valves (BHV) has been limited by their failure due to calcification. 1,2 Various anticalcification agents have been used in a range of therapeutic approaches including preincubations, systemic administration, or local sitespecific administration. Even though ethanol is the most effective anticalcification agent found nonclinically and is now clinically applied for prevention of BHV calcification, its anticalcification activity is far from complete for the specific compartments of BHV, such as aortic wall.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CEM calcification by the sequential pretreatment with ethanol and EDTA

Singla

Lee

2003

J Biomedical Materials Res

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The major object of the present study is to optimize the anticalcification activity of ethanol on bioprosthetic heart valve (BHV) calcification. We hypothesize that the chelating agent, in combination with ethanol, will synergistically prevent aortic wall calcification. Collagen-elastin matrix (CEM) was developed as a calcifiable matrix for simulating the calcification process of implantable biomaterials. The efficacy of the combination effects of ethanol and EDTA on the calcification process of CEMs was investigated by implanting them after pretreatment with various conditions of ethanol and EDTA in the rat subdermal model. The relationship between calcium concentrations and pretreatment conditions (a series vs. simultaneous, i.e., first ethanol and then EDTA in water solution, the reverse, or EDTA in ethanol) was established and the optimal condition for prevention of BHV calcification was determined. The mechanistic studies on anticalcification effects exerted by particular pretreatment sequences were also conducted using FTIR and differential scanning calorimetry (DSC). The sequential pretreatment of CEM first with ethanol and then EDTA in water solution significantly decreased the calcification rate of CEM compared the control. The percentage of prevention of calcification by the serial treatment of ethanol (80% v/v) and then EDTA in water solutions decreased, as the concentration of elastin in the CEM increased. The percentage of preventing calcification was 42%, 28.6%, and 22.9% for CEM containing collagen and elastin ratios of 90:10, 50:50, 20:80, respectively. These results indicate that elastin is the major regulatory component of BHV calcification, and preventive effects on calcification increased only when CEM were pretreated with first ethanol and then EDTA in water solution. Moreover, the sequential effect is more apparent in the matrix of less elastin content, which is close to the physiological range. The sequential inhibitory effects of ethanol and EDTA could occur due to the distinct separate actions of each agent, thereby achieving a relatively greater inhibition of calcification.

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Antimineralization treatments for bioprosthetic heart valves

Cited by 57 publications

References 20 publications

Inhibition of aortic wall calcification in bioprosthetic heart valves by ethanol pretreatment: Biochemical and biophysical mechanisms

Inhibition of aortic wall calcification in bioprosthetic heart valves by ethanol pretreatment: Biochemical and biophysical mechanisms

Pharmaceutical and Biomedical Applications of Interpenetrating Polymer Network

Inhibition of CEM calcification by the sequential pretreatment with ethanol and EDTA

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