Effects of enzyme-based removal of collagen and elastin constituents on the biaxial mechanical responses of porcine atrioventricular heart valve anterior leaflets

Ross, Colton J.; Laurence, Devin W.; Echols, Allyson; Babu, Anju R.; Gu, Tingting; Duginski, Grace A.; Johns, Cortland H.; Mullins, Brennan T.; Casey, Katherine M.; Laurence, Keely A.; Zhao, Yan; Amini, Rouzbeh; Fung, Kar‐Ming; Mir, Arshid; Burkhart, Harold M.; Wu, Yi; Holzapfel, Gerhard; Lee, Chung‐Hao

doi:10.1016/j.actbio.2021.08.043

Cited by 13 publications

(9 citation statements)

References 56 publications

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“…The soaking and resting procedure was applied for both the elastase group (n e = 10) and the control group (n c = 10); in the latter group, PBS was used in lieu of the elastase solution. The 20-minute elastase application time was consistent with previous research involving carotid artery and atrioventricular valves [23,31]. We have also shown that no traces of elastin was visually detectable in our examined samples.…”

Section: Elastase Applicationsupporting

confidence: 91%

The role of elastin on the mechanical properties of the anterior leaflet in porcine tricuspid valves

et al. 2022

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Elastin is present in the extracellular matrix (ECM) of connective tissues, and its mechanical properties are well documented. In Marfan syndrome, however, the inability to properly code for the protein fibrillin-1 prematurely leads to the degradation and loss of elastin fiber integrity in the ECM. In this study, the role of elastin in the ECM of the anterior leaflet of the tricuspid valve was investigated by examining the biomechanical behavior of porcine leaflets before and after the application of the enzyme elastase. Five loading protocols were applied to the leaflet specimens in two groups (elastase-treated and control samples). The mechanical response following elastase application yielded a significantly stiffer material in both the radial and circumferential directions. At a physiological level of stress (85 kPa), the elastase group had an average strain of 26.21% and 6.32% in the radial and circumferential directions, respectively, at baseline prior to elastase application. Following elastase treatment, the average strain was 5.28% and 0.97% in the radial and circumferential directions, respectively. No statistically significant change was found in the control group following sham treatment with phosphate-buffered saline (PBS). Two-photon microscopy images confirmed that after the removal of elastin, the collagen fibers displayed a loss of undulation. With a significant reduction in radial compliance, the ability to withstand physiological loads may be compromised. As such, an extracellular matrix that is structurally deficient in elastin may hinder normal tricuspid valve function.

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Section: Elastase Applicationsupporting

confidence: 91%

The role of elastin on the mechanical properties of the anterior leaflet in porcine tricuspid valves

et al. 2022

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“…For direct comparison with their untreated counterpart, once the samples were tested, each lung region’s samples were equally divided into a collagenase and elastase group and treated (Worthington Biochemical Corp.). The enzymatic solutions were prepared using deionized water with a concentration of 96 units/ml for collagenase and 0.1 units/ml for elastase including 0.001 mg/ml Trypsin inhibitor [ 49 ]. Both solutions were mixed using a thermal shaker at 100RPM and 37 ℃.…”

Section: Methodsmentioning

confidence: 99%

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

et al. 2023

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Background Common respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date. Methods Specimens were extracted from the proximal and distal airways, namely the trachea, large bronchi, and small bronchi to facilitate evaluations of material heterogeneity, and subjected to biaxial planar loading in the circumferential and axial directions to assess airway anisotropy. Next, samples were subjected to collagenase and elastase enzymatic treatment and tensile tests were repeated. Airway tissue mechanical properties pre- and post-treatment were comprehensively characterized via measures of initial and ultimate moduli, strain transitions, maximum stress, hysteresis, energy loss, and viscoelasticity to gain insights regarding the specialized role of individual connective tissue fibers and network interactions. Results Enzymatic treatment demonstrated an increase in airway tissue compliance throughout loading and resulted in at least a 50% decrease in maximum stress overall. Strain transition values led to significant anisotropic manifestation post-treatment, where circumferential tissues transitioned at higher strains compared to axial counterparts. Hysteresis values and energy loss decreased after enzymatic treatment, where hysteresis reduced by almost half of the untreated value. Anisotropic ratios exhibited axially led stiffness at low strains which transitioned to circumferentially led stiffness when subjected to higher strains. Viscoelastic stress relaxation was found to be greater in the circumferential direction for bronchial airway regions compared to axial counterparts. Conclusion Targeted fiber treatment resulted in mechanical alterations across the loading range and interactions between elastin and collagen connective tissue networks was observed. Providing novel mechanical characterization of elastase and collagenase treated airways aids our understanding of individual and interconnected fiber roles, ultimately helping to establish a foundation for constructing constitutive models to represent various states and progressions of pulmonary disease.

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“…Upon further stretching, convoluted collagen fibers are straightened [ 68 ]. After that, the collagen fibers begin to resist deformation, and in the absence of tension, elastin returns them to a convoluted state [ 68 , 69 ]. The elasticity of synthetic polymer materials is ensured by chain straightening and the motion of macromolecules relative to each other, as well as the ability of the molecule to assume a more energetically favorable state [ 70 ].…”

Section: Historical Backgroundmentioning

confidence: 99%

Polymeric Heart Valves Will Displace Mechanical and Tissue Heart Valves: A New Era for the Medical Devices

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Klyshnikov

Грицкевич³

et al. 2023

IJMS

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The development of a novel artificial heart valve with outstanding durability and safety has remained a challenge since the first mechanical heart valve entered the market 65 years ago. Recent progress in high-molecular compounds opened new horizons in overcoming major drawbacks of mechanical and tissue heart valves (dysfunction and failure, tissue degradation, calcification, high immunogenic potential, and high risk of thrombosis), providing new insights into the development of an ideal artificial heart valve. Polymeric heart valves can best mimic the tissue-level mechanical behavior of the native valves. This review summarizes the evolution of polymeric heart valves and the state-of-the-art approaches to their development, fabrication, and manufacturing. The review discusses the biocompatibility and durability testing of previously investigated polymeric materials and presents the most recent developments, including the first human clinical trials of LifePolymer. New promising functional polymers, nanocomposite biomaterials, and valve designs are discussed in terms of their potential application in the development of an ideal polymeric heart valve. The superiority and inferiority of nanocomposite and hybrid materials to non-modified polymers are reported. The review proposes several concepts potentially suitable to address the above-mentioned challenges arising in the R&D of polymeric heart valves from the properties, structure, and surface of polymeric materials. Additive manufacturing, nanotechnology, anisotropy control, machine learning, and advanced modeling tools have given the green light to set new directions for polymeric heart valves.

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Effects of enzyme-based removal of collagen and elastin constituents on the biaxial mechanical responses of porcine atrioventricular heart valve anterior leaflets

Cited by 13 publications

References 56 publications

The role of elastin on the mechanical properties of the anterior leaflet in porcine tricuspid valves

The role of elastin on the mechanical properties of the anterior leaflet in porcine tricuspid valves

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

Polymeric Heart Valves Will Displace Mechanical and Tissue Heart Valves: A New Era for the Medical Devices

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