Glycosaminoglycan-targeted fixation for improved bioprosthetic heart valve stabilization

Mercuri, Jeremy; Lovekamp, Joshua J.; Simionescu, Dan T.; Vyavahare, Narendra R.

doi:10.1016/j.biomaterials.2006.09.005

Cited by 33 publications

(54 citation statements)

References 30 publications

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“…GAGs have been previously found to be lost from BHVs after storage [11]. This becomes an important issue as valves may be stored for up to 3 years prior to implantation.…”

Section: Resultsmentioning

confidence: 99%

“…We have shown that other fixatives such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and sodium metaperiodate are only partially effective in preventing GAG loss against GAG-degrading enzymes [11, 14]. Neomycin trisulfate, a hyaluronidase inhibitor, has been incorporated in the tissue with carbodiimide fixation chemistry to prevent the enzyme-mediated GAG degradation.…”

Section: Introductionmentioning

confidence: 99%

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Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

2009

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Bioprosthetic heart valve (BHV) cusps have a complex architecture consisting of an anisotropic arrangement of collagen, glycosaminoglycans (GAGs) and elastin. Glutaraldehyde (GLUT) is used as a fixative for all clinical BHV implants; however, it only stabilizes the collagen component of the tissue, and other components such as GAGs and elastin are lost from the tissue during processing, storage or after implantation. We have shown previously that the effectiveness of the chemical crosslinking can be increased by incorporating neomycin trisulfate, a hyaluronidase inhibitor, to prevent the enzyme-mediated GAG degradation. In the present study, we optimized carbodiimidebased GAG-targeted chemistry to incorporate neomycin into BHV cusps prior to conventional GLUT crosslinking. This crosslinking leads to enhanced preservation of GAGs during in vitro cyclic fatigue and storage. The neomycin group showed greater GAG retention after both 10 and 50 million accelerated-fatigue cycles and after 1 year of storage in GLUT solution. Thus, additional binding of neomycin to the cusps prior to standard GLUT crosslinking could enhance tissue stability and thus heart valve durability.

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“…GAGs have been previously found to be lost from BHVs after storage [11]. This becomes an important issue as valves may be stored for up to 3 years prior to implantation.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

2009

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“…Incubation at room temperature for 45 minutes yielded a color product indicative of hexosamine quantities, which was read for absorbance at 540 nm with a set of D (+) glucosamine (0–200 µg) controls. All values were normalized to their respective dry tissue weights and corrected for the fact that hexosamine assay accounts for ~90 µg / 10 mg of non-GAG related hexosamines as previously done [31, 33]. …”

Section: Methodsmentioning

confidence: 99%

On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet

et al. 2013

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While the role of collagen and elastin fibrous components in heart valve valvular biomechanics has been extensively investigated [see Sacks et al. 2009 J. Biomech. 42, 1804-24], the biomechanical role of the glycosaminoglycan (GAG) gelatinous-like material phase remains unclear. In the present study, we investigated the biomechanical role of GAGs in porcine aortic valve (AV) leaflets under tension utilizing enzymatic removal. Tissue specimens were removed from the belly region of porcine AVs and subsequently treated with either an enzyme solution for GAG removal, or a control (buffer with no enzyme) solution. A dual stress level test methodology was used to determine the effects at low and high (physiological) stress levels). In addition, planar biaxial tests were conducted both on-axis (i.e. aligned to the circumferential and radial axes) and at 45° off-axis to induce maximum shear, to explore the effects of augmented fiber rotations on the fiber-fiber interactions. Changes in hysteresis were used as the primary metric of GAG functional assessment. A simulation of the low force experimental setup was also conducted to clarify the internal stress system and provide viscoelastic model parameters fo this loading range. Results indicated that under planar tension the removal of GAGs had no measureable affect extensional mechanical properties (either on- or 45° off-axis) including peak stretch, hysteresis, or creep. Interestingly, in the low force range, hysteresis was markedly reduced from 35.96 ± 2.65% in control group to 25.00 ± 1.64% (p < 0.001) as a result of GAG removal. Collectively, these results suggest that GAGs do not play a direct role in modulating the time-dependent tensile properties of valvular tissues. Rather, they appear to be strongly connected with fiber-fiber and fiber-matrix interactions at low forces levels. Thus, we speculate that GAGs may be important in providing a damping mechanism to reduce leaflet flutter when the leaflet is not under high tensile stress.

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“…151 Genipin, a naturally occurring crosslinking agent, and carbodiimide were found to be effective crosslinking agents but produce distinct crosslinking structures, which may in turn affect other properties of the fixed tissue (Table 5). 199 Mercuri et al 137 looked into GAG-targeted fixation which allowed for higher retention of GAGs, but did not alter the calcification potential of the leaflets compared to conventional GLUT-treated tissue.…”

Section: Effect Of Exogenous Cross-linking As a Means For Tissue Presmentioning

confidence: 99%

Biomechanical Behavior of Bioprosthetic Heart Valve Heterograft Tissues: Characterization, Simulation, and Performance

Soares

Feaver

Zhang

et al. 2016

Cardiovasc Eng Tech

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The use of replacement heart valves continues to grow due to the increased prevalence of valvular heart disease resulting from an ageing population. Since bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve, there continues to be a strong need to develop better and more reliable BHVs through and improved the general understanding of BHV failure mechanisms. The major technological hurdle for the lifespan of the BHV implant continues to be the durability of the constituent leaflet biomaterials, which if improved can lead to substantial clinical impact. In order to develop improved solutions for BHV biomaterials, it is critical to have a better understanding of the inherent biomechanical behaviors of the leaflet biomaterials, including chemical treatment technologies, the impact of repetitive mechanical loading, and the inherent failure modes. This review seeks to provide a comprehensive overview of these issues, with a focus on developing insight on the mechanisms of BHV function and failure. Additionally, this review provides a detailed summary of the computational biomechanical simulations that have been used to inform and develop a higher level of understanding of BHV tissues and their failure modes. Collectively, this information should serve as a tool not only to infer reliable and dependable prosthesis function, but also to instigate and facilitate the design of future bioprosthetic valves and clinically impact cardiology.

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Glycosaminoglycan-targeted fixation for improved bioprosthetic heart valve stabilization

Cited by 33 publications

References 30 publications

Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet

Biomechanical Behavior of Bioprosthetic Heart Valve Heterograft Tissues: Characterization, Simulation, and Performance

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