Category: General

Biomaterials. 2022 Sep 6;289:121782. doi: 10.1016/j.biomaterials.2022.121782. Online ahead of print.

ABSTRACT

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP.

PMID:36099713 | DOI:10.1016/j.biomaterials.2022.121782

Xenotransplantation. 2022 Sep 13:e12774. doi: 10.1111/xen.12774. Online ahead of print.

ABSTRACT

INTRODUCTION: Current bioprosthetic heart valve replacement options are limited by structural valvular deterioration (SVD) due to an immune response to the xenogenic scaffold. Autologous mesenchymal stem cell (MSC) recellularization is a method of concealing xenogenic scaffolds, preventing recipient immune recognition of xenogenic tissue heart valves, and potentially leading to reduction in SVD incidence. The purpose of this study is to examine the effects of autologous MSC recellularized tissue on the immune response of human whole blood to bovine pericardium (BP). We hypothesized that autologous MSC recellularization of BP will result in reduced pro-inflammatory cytokine production equivalent to autologous human pericardium.

METHODS: Bone marrow, human pericardium, and whole blood were collected from adult patients undergoing elective cardiac surgery. Decellularized BP underwent recellularization with autologous MSCs, followed by co-incubation with autologous whole blood. Immunohistochemical, microscopic, and quantitative immune analysis approaches were used.

RESULTS: We demonstrated that native BP, exposed to human whole blood, results in significant TNF-α and IL1β production. When decellularized BP is recellularized with autologous MSCs and exposed to whole blood, there is a significant reduction in TNF-α and IL1β production. Importantly, recellularized BP exposed to whole blood had similar production of TNF-α and IL1β when compared to autologous human pericardium exposed to human whole blood.

CONCLUSION: Our results suggest that preventing initial immune activation with autologous MSC recellularization may be an effective approach to decrease the recipient immune response, preventing recipient immune recognition of xenogeneic tissue engineered heart valves, and potentially leading to reduction in SVD incidence.

PMID:36098060 | DOI:10.1111/xen.12774

J Cerebrovasc Endovasc Neurosurg. 2022 Sep 7. doi: 10.7461/jcen.2022.E2020.11.004. Online ahead of print.

ABSTRACT

Vascular compression of neural tissue causing neurological symptoms is a wellknown phenomenon. This is commonly seen in trigeminal neuralgia and, less commonly, in hemifacial spasm by small arteries, which can be treated by microvascular decompression. Rarely, larger arteries, such as the vertebral arteries, may compress the brainstem. This can lead to symptoms of pontine or medullary distress like hemiparesis, dysphagia, or respiratory distress. This is treated by macrovascular decompression. Due to the rare and heterogenous nature of this disease, there is no standardized approach. We describe a novel technique whereby the vertebrobasilar system is mobilized anterolaterally towards the occipital condyle with a sling to decompress the brainstem. We report two cases of vertebrobasilar dolichoectasia causing brainstem compression. A carotid patch graft sling with anterolateral mobilization to the occipital condyle is described as a surgical nuance to macrovascular decompressive surgery. Briefly, the vertebral artery was identified and dissected away from the brainstem and the bulbar cranial nerves. Bovine pericardium graft was used to create a sling around the artery by suturing the two ends together. The sling was then fixed either to the occipital condyle using cranial plating screws or suturing to the dura of the occipital condyle. A novel surgical technique for management of vertebrobasilar dolichoectasia causing brainstem compression with progressive neurological deterioration is reported. Anatomical location and the offending vessel should guide neurosurgeons to select the best surgical option to achieve complete decompression of the involved neural structures.

PMID:36068675 | DOI:10.7461/jcen.2022.E2020.11.004

World J Pediatr Congenit Heart Surg. 2022 Sep;13(5):581-587. doi: 10.1177/21501351221116766.

ABSTRACT

The disadvantage of right ventricle-to-pulmonary artery (RV-PA) shunt is the need for more unplanned interventions to address stenosis in the shunt or branch pulmonary arteries, as compared to the modified Blalock-Taussig shunt group. Ring-enforced RV-PA PTFE conduit and dunk technique minimized these complications and right ventricle (RV) damage. Aortic arch obstruction increases afterload and leads to ventricular dysfunction and tricuspid regurgitation; therefore, most surgeons prefer to use homograft, autologous pericardium, or bovine pericardium to reconstruct the neoaorta. Artificial materials decrease the elastic properties, increase wall stiffness, and decrease the distensibility of the aorta; and as a result, RV function gradually deteriorates. This inelastic reconstructed aorta may be one of the reasons why long-term outcomes after the Fontan procedure are worse in hypoplastic left heart syndrome (HLHS) patients, in comparison to non-HLHS. Reconstruction of the neoaorta without any patch materials, or at least techniques that largely minimize the use of non-autologous materials, will offer a further refinement of our ability to optimize ventriculoarterial coupling and thereby long-term RV function.

PMID:36053099 | DOI:10.1177/21501351221116766

Acta Biomater. 2022 Aug 30:S1742-7061(22)00540-2. doi: 10.1016/j.actbio.2022.08.057. Online ahead of print.

ABSTRACT

Chemically crosslinked acellular bovine pericardium (ABP) has been widely used in clinical practice as bioprostheses. To ensure its consistency and durability, crosslinkers are used in excess, with stability guided by indicators including the hydrothermal denaturation temperature, the enzymatic resistance and the degree of crosslinking. Yet, understanding of the intermolecular structure in collagen fibrils which imparts the intrinsic stability of the ABPs is lacking, and the discrepancies in the stability criteria in varied conditions are poorly explained. In this study, synchrotron small-angle X-ray scattering (SAXS) in combination with thermal and colorimetric methods are employed to investigate the changes in the structure and the stability of ABPs during crosslinking using glutaraldehyde (GA) or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) at different concentrations. Based on the findings, a mechanism is proposed to explicate the crosslinking effects on collagen structure and the relationship between the structure and each stability indicator. At low crosslinker concentrations, the telopeptidyl-helical linkages are preferred, which cause rearrangements in the intermolecular structure of collagen, and efficiently contribute to its stabilities. Excess crosslinking is revealed by a revert trend in structural changes and the plateauing of the stabilities, assigning to the helical-helical linkages and monovalent bindings. The former would improve thermal stability but not collagenase resistance, whereas the latter have negligible effects. Overall, this study provides a mechanistic understanding of the chemical crosslinking of ABPs, which will contribute to the future development of more efficient and economically viable strategies to produce bioprostheses. STATEMENT OF SIGNIFICANCE: Chemical crosslinking imparts suitable properties to acellular bovine pericardium (ABP) for clinical applications, yet the understanding is lacking on the structure-stability relationship especially under different crosslinking conditions. Structural evidence in this study differentiates the binding sites during crosslinking in collagen fibrils at different crosslinker concentrations, highlighting the excess usage in the conventional crosslinking treatments. The mechanism based on the structure of collagen also successfully explains the dissimilarity in hydrothermal and enzymatic stabilities with varied crosslinking conditions. Future researches focusing on developing biomaterials via chemical crosslinking of ABPs would benefit from this study, for its contribution to the better understanding of the relationship of collagen structure and functions.

PMID:36049624 | DOI:10.1016/j.actbio.2022.08.057

J Cardiovasc Dev Dis. 2022 Aug 22;9(8):282. doi: 10.3390/jcdd9080282.

ABSTRACT

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a look at the future. Durability, low thrombogenicity, good hydrodynamics, biocompatibility, low catheter profile, and deployment stability are the attributes of an ideal TAVI device. Two main design types exist-balloon-expandable and self-expanding prostheses. Balloon-expandable prostheses use a cobalt-chromium alloy frame providing high radial strength and radiopacity, while the self-expanding prostheses use a nickel-titanium (Nitinol) alloy frame, which expands to its original shape once unsheathed and heated to the body temperature. The valve is sewn onto the frame and consists of the porcine or bovine pericardium, which is specially treated to prevent calcinations and prolong durability. The lower part of the frame can be covered by polyethylene terephthalate fabric or a pericardial skirt, providing better sealing between the frame and aortic annulus. The main future challenges lie in achieving lower rates of paravalvular leaks and new pacemaker implantations following the procedure, lower delivery system profiles, more precise positioning, longer durability, and a good hemodynamic profile. Patient-specific design and the use of autologous tissue might solve these issues.

PMID:36005446 | PMC:PMC9409777 | DOI:10.3390/jcdd9080282

Biomimetics (Basel). 2022 Aug 1;7(3):104. doi: 10.3390/biomimetics7030104.

ABSTRACT

Human and animal pericardia are among the most widely exploited materials suitable to repair damaged tissues in the cardiovascular surgery context. Autologous, xenogeneic (chemically treated) and homologous pericardia are largely utilized, but they do exhibit some crucial drawbacks. Any tissue treated with glutaraldehyde is known to be prone to calcification in vivo, lacks regeneration potential, has limited durability, and can result in cytotoxicity. Moreover, autologous tissues have limited availability. Decellularized biological tissues represent a promising alternative: decellularization removes cellular and nuclear components from native tissues and makes them suitable for repopulation by autologous cells upon implantation into the body. The present work aims to assess the effects of a new detergent, i.e., Tergitol, for decellularizing bovine and porcine pericardia. The decellularization procedure successfully removed cells, while preserving the histoarchitecture of the extracellular matrix. No cytotoxic effect was observed. Therefore, decellularized pericardia showed potential to be used as scaffold for cardiovascular tissue regeneration.

PMID:35997424 | PMC:PMC9397045 | DOI:10.3390/biomimetics7030104

Comput Methods Biomech Biomed Engin. 2022 Aug 11:1-10. doi: 10.1080/10255842.2022.2110378. Online ahead of print.

ABSTRACT

Leaflet damage has been documented to occur while deploying a transcatheter aortic valve (TAV) due to mechanical loads during the crimping procedures. In this study, the impact of compressive stress on folded leaflets was measured to investigate the mechanism of traumatic leaflet tissue damage. Numerical simulation of TAV crimping procedure was adapted to calculate stress magnitude and distribution of leaflets. A 20 mm balloon expanding short stent TAV with 0.25 mm thickness leaflets was used in the simulation. Then the calculated stresses were applied on leaflet material (bovine pericardium) samples by loading experiments. Mechanical properties evaluation combined with histological and microscopy observation were used to investigate the tissue damage. The elastic modulus and the tensile strength of the tissue began to decrease significantly at 2 MPa stress and 2.5 MPa stress, respectively. No significant differences were observed at 0-1.5 MPa stress. When the TAV was crimped to 14 Fr and 12 Fr, the 2 MPa greater areas on leaflets increased from 18.17% to 76.96%. 2 MPa compressive stress might be the threshold value for leaflet damage. The TAV crimping size should be paid attention to avoid the compressive stress higher than 2 MPa.

PMID:35951008 | DOI:10.1080/10255842.2022.2110378

Front Bioeng Biotechnol. 2022 Sep 9;10:1008664. doi: 10.3389/fbioe.2022.1008664. eCollection 2022.

ABSTRACT

The bioprosthetic heart valves (BHVs) are the best option for the treatment of valvular heart disease. Glutaraldehyde (Glut) is commonly used as the golden standard reagent for the crosslinking of BHVs. However, the obvious defects of Glut, including residual aldehyde toxicity, degradation and calcification, increase the probability of valve failure in vivo and motivated the exploration of alternatives. Thus, the aim of this study is to develop a non-glutaraldehyde hybrid cross-linking method composed of Neomycin Trisulfate, Polyethylene glycol diglycidyl ether and Tannic acid as a substitute for Glut, which was proven to reduce calcification, degradation, inflammation of the biomaterial. Evaluations of the crosslinked bovine pericardial included histological and ultrastructural characterization, biomechanical performance, biocompatibility and structural stability test, and in vivo anti-inflammation and anti-calcification assay by subcutaneous implantation in juvenile Sprague Dawley rats. The results revealed that the hybrid crosslinked bovine pericardial were superior to Glut crosslinked biomaterial in terms of better hydrophilicity, thermodynamics stability, hemocompatibility and cytocompatibility, higher Young’s Modulus, better stability and resistance to enzymatic hydrolysis, and lower inflammation, degradation and calcification levels in subcutaneous implants. Considering all above performances, it indicates that the hybrid cross-linking method is appropriate to replace Glut as the method for BHV preparation, and particularly this hybrid crosslinked biomaterials may be a promising candidate for next-generation BHVs.

PMID:36159659 | PMC:PMC9500414 | DOI:10.3389/fbioe.2022.1008664

Curr Probl Cardiol. 2022 Sep 22:101413. doi: 10.1016/j.cpcardiol.2022.101413. Online ahead of print.

ABSTRACT

Mitral Regurgitation (MR) is the most common form of severe valvular disease occurring in developed countries, being caused either primarily on its own or secondary to cardiac disease. Surgical intervention is required for the correction of MR, which could include the replacement or repair of the affected valve. Transcatheter Mitral Valve Replacement (TMVR) in selected patients is of increasing importance, especially after the success of Transcatheter Aortic Valve Replacement (TAVR). TMVR can be divided into three types i.e., valve-in-valve (ViV) for severe mitral valve disease, valve-in-ring (ViR) for failed surgical repairs, and valve-in-mitral annular calcifications (ViMAC) for mitral valvular disease with severe mitral annular calcifications and poor surgical criteria. The FDA approved Mitral ViV for patients with a high surgical risk in 2017, while ViR and ViMAC are still currently under consideration. The SAPIEN M3 valve is relatively new with a trans-septal system, with a success rate of 86%, and no mortality in a 30-day outcome. The Cardiovalve is a bovine pericardium device that has a dual nitinol frame with a custom surgical design to facilitate TMVR. The AHEAD trial will evaluate whether the device is safe to use in a clinical setting and how effective it is for reducing MR in these patients. The trial consists of 30 patients in which the first 5 patients showed 100% technical success and a reduction of MR. This evolution of modern medicine has assisted in many different countries, including Pakistan where there is a higher prevalence of MR and hence, a greater need to apply TMVR in clinical practice.

PMID:36155202 | DOI:10.1016/j.cpcardiol.2022.101413