Biological Heart Valve Research Articles

Characterization of acid and non-acid glycosphingolipids of porcine heart valve cusps as potential immune targets in biological heart valve grafts.

Although xenotransplantation of vascularized organs/cells has not yet reached the clinic, glutaraldehyde-treated bioprosthetic heart valves (BHV), derived from porcine or bovine tissues, are today used for clinical replacement of diseased heart valves. However, the durability of these valve cusps is limited partly due to the onset of immune responses to the grafts. The xenoantigen-determinant Galα3Gal- and corresponding anti-Gal antibodies have been postulated to in part contribute to BHV damage. However, the presence of other non-Gal carbohydrate antigen determinants as well as the immune response to these non-Gal antigens and the inflammatory response generated by their interaction with the immune system has not been studied. In this study, we have isolated and structurally characterized both non-acid and acid glycosphingolipids from naïve porcine aortic and pulmonary valve cusps. Total non-acid and acid glycosphingolipids were isolated from porcine aortic and pulmonalis valve cusps of 20 animals. Glycosphingolipid components were structurally characterized by thin-layer chromatography, liquid chromatography-mass spectrometry and binding of monoclonal antibodies and lectins. The non-acid glycosphingolipids were characterized as globotetraosylceramide, H-type 2 pentaosylceramide, fucosyl-gangliotetraosylceramide, and Galα3neolactotetraosylceramide. The acid glycosphingolipid fractions had both sulfatide and gangliosides (GM3, GM2, GM1, fucosyl-GM1, GD3 and GD1a), and all gangliosides contained N-acetyl-neuraminic acid. Significantly, the N-glycolyl-neuraminic acid (NeuGc) variant, a major component in many pig organs and to which humans can develop antibodies, was not detected among the gangliosides. Pig valve cusps contain several complex lipid-bound carbohydrate structures that may be targets for the human immune system. Notable, the NeuGc determinant was absent in the cusp gangliosides. This work forms a platform for further characterizing the antibody reactivity of patients with porcine-derived BHV.

The Biological Heart Valve in Aortic Position and its Effect on the Brain

The Biological Heart Valve in Aortic Position and its Effect on the Brain

The degeneration of biological cardiovascular prostheses under pro-calcific metabolic conditions in a small animal model

In order to allow for a comparative evaluation of the in vivo degeneration of biological and tissue-engineered heart valves and vascular grafts, a small animal model of accelerated cardiovascular calcification is desired. Wistar rats (n = 102; 6 groups) were fed ad libitum with regular chow and 5 different regimens of pro-calcific diet supplemented with combinations of vitamin D (VD), cholesterol (CH) and dicalcium phosphate (PH). Moreover, cryopreserved (n = 7) or detergent-decellularized rat aortic conduit grafts (n = 6) were infrarenally implanted in Wistar rats under severely pro-calcific conditions. The follow-up lasted up to 12 weeks. High-dose application of VD (300,000 IU/kg), CH (2%) and PH (1.5%) resulted in elevated serum calcium and cholesterol levels as well as LDL/HDL ratio. It increased the tissue MMP activity visualized by in situ zymography and caused significantly aggravated calcification of the native aortic valve as well as the aortic wall as assessed by histology and micro-computed tomography. (Immuno)histology and quantitative real-time PCR revealed chondro-osteogenic cell transformation, lipid deposition, nitrosative stress and low-level inflammation to be involved in the formation of calcific lesions. Despite pro-calcific in vivo conditions, decellularization significantly reduced calcification, inflammation and intimal hyperplasia in aortic conduit implants. A well balanced dietary trigger for pathologic metabolic conditions may represent an appropriate mid-term treatment to induce calcifying degeneration of aortic valves as well as vascular structures in the systemic circulation in rats. With respect to experimental investigation focusing on calcifying degeneration of native or prosthetic tissue, this regimen may serve as a valuable tool with a rapid onset and multi-facetted character of cardiovascular degeneration.

Welche Herzklappe für welchen Patienten – Selektion der Klappen interventionell und konventionell

Prosthesis choice for aortic or mitral valve replacement should be individualized and discussed by an interdisciplinary heart team and the informed patient. Taking into account the age, comorbidities, compliance and lifestyle of the patient, the heart team should evaluate if a patient can undergo mechanical or biological conventional heart valve replacement, or if a catheter based procedure should be offered. A mechanical valve is indicated if the patient already has a mechanical valve, or if there is an increased risk for degeneration of a biological prosthesis, and if there are no contraindications for lifelong anticoagulation. A biological valve is indicated if good quality anticoaguloation is unlikely, bleeding risk is increased, or previous mechanical valve thrombosis has occurred. A bioprosthesis should also be considered in young women contemplating pregnancy. Transcatheter valve procedures (TAVI) are an alternative to the conventional procedure in patients with high surgical risk. The experience of the heart team is of utmost importance for the assessment and decision making. The results of ongoing large randomized trials will further specify the indications for TAVI.

Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H2O and CO2. Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid.

Cytotoxicity of PVPAC‐treated bovine pericardium: A potential replacement for glutaraldehyde in biological heart valves

Acellular biological tissues, including bovine pericardium (BP), have been proposed as biomaterial for tissue engineering. BP is usually modified chemically to improve mechanical and biological properties using glutaraldehyde, the standard reagent for preservation of fresh bioprosthetic materials. Glutaraldehyde-fixed BP (Glut-BP), the most widely used material in heart valve manufacture, has been associated with calcification in vivo. In an attempt to reduce this issue and maintain its biocompatibility, this study assesses the physical properties and cytotoxicity of lyophilized BP treated with poly (vinylpyrrolidone-co-acrolein) (PVPAC-BP), a novel copolymer, as a substitute for glutaraldehyde. For that, PVPAC-BP surface ultrastructure, elastic function, water uptake and tissue calcification were evaluated. For the analysis of biocompatibility, fibroblasts (3T3-L1) and endothelial cells (HUVEC) were cultured on PVPAC-BP, Untreated-BP and Glut-BP. Nitric oxide (NO) release assay, fluorescence and SEM images of endothelial cells adhered on scaffolds were also performed. As results, the data show some advantages of PVPAC-BP over the Glut-BP. The PVPAC-BP maintains partially the original ultrastructure and elastic properties, improves scaffold hydration, and presents less calcium phosphate deposits. The cells demonstrated strong attachment, high proliferation rate, and formation of a monolayer on PVPAC-BP. Attached cells were also able to release NO de-monstrating regular metabolism. In conclusion, PVPAC may be considered as a promising alternative to BP treatment improving the efficiency of cell attachment and proliferation and also avoid immunogenicity.

Early clinical outcome of aortic transcatheter valve-in-valve implantation in the Nordic countries

Transcatheter valve-in-valve implantation has emerged as an option, in addition to reoperative surgical aortic valve replacement, to treat failed biologic heart valve substitutes. However, the clinical experience with this approach is still limited. We report the comprehensive experience of transcatheter valve-in-valve implantation in the Nordic countries from May 2008 to January 2012. A total of 45 transcatheter aortic valve-in-valve implantations were performed during the study period in 11 centers. The mean age of the patients was 80.6 years (range, 61-91), 26 were male and 19 were female, and the mean EuroSCORE, EuroSCORE II, and Society of Thoracic Surgeons score was 35.4, 16.3, and 14.6, respectively. The type of failure was stenosis and combined in 58% (mean and peak aortic valve gradient, 77 and 45 mm Hg, respectively) and regurgitation in 42% of cases. The SAPIEN/XT (Edwards LifeSciences, Irvine, Calif) and CoreValve (Medtronic Inc, Minneapolis, Minn) system was used in 33 and 12 cases, respectively. The access route was transapical in 25, transfemoral in 17, transaortic in 2, and subclavian in 1 case. The mean follow-up was 14.4 months. The periprocedural and postoperative outcomes were assessed using the Valve Academic Research Consortium criteria. No intraprocedural mortality occurred. The technical success rate was 95.6% (1 second valve implantation, 1 conversion to open surgery). The all-cause 30-day mortality was 4.4% (1 cardiac-related and 1 aspiration pneumonia). The major complications within 30 days included stroke in 2.2%, periprocedural myocardial infarction in 4.4%, and major vascular complication in 2.2% of patients. At 1 month, all but 1 patient had either no or mild paravalvular leakage, with a mean and peak valve gradient of 17 mm Hg (range, 4-38) and 30 mm Hg (range, 7-68), respectively. The mean gradient was greater than 20 mm Hg in 17% of patients and remained unchanged at 12 months. The 1-year survival was 88.1%. Transcatheter valve-in-valve implantation is widely performed, albeit in small numbers, in most centers in the Nordic countries. The short-term results were excellent in this high-risk patient population, demonstrating a low incidence of device- or procedure-related complications. However, a considerable number of patients were left with suboptimal systolic valve performance with unknown long-term effects, warranting close surveillance after transcatheter valve-in-valve implantation.

Characterisation of antibody responses to Gal-positive and Gal-free biological heart valves

Characterisation of antibody responses to Gal-positive and Gal-free biological heart valves

Noninvasive Analysis of Synthetic and Decellularized Scaffolds for Heart Valve Tissue Engineering

Microcomputed tomography (µ-CT) is a nondestructive, high-resolution, three-dimensional method of analyzing objects. The aim of this study was to evaluate the feasibility of using µ-CT as a noninvasive method of evaluation for tissue-engineering applications. The polyurethane aortic heart valve scaffold was produced using a spraying technique. Cryopreserved/thawed homograft and biological heart valve were decellularized using a detergent mixture. Human endothelial cells and fibroblasts were derived from saphenous vein segments and were verified by immunocytochemistry. Heart valves were initially seeded with fibroblasts followed by colonization with endothelial cells. Scaffolds were scanned by a µ-CT scanner before and after decellularization as well as after cell seeding. Successful colonization was additionally determined by scanning electron microscopy (SEM) and immunohistochemistry (IHC). Microcomputed tomography accurately visualized the complex geometry of heart valves. Moreover, an increase in the total volume and wall thickness as well as a decrease in total surface was demonstrated after seeding. A confluent cell distribution on the heart valves after seeding was confirmed by SEM and IHC. We conclude that µ-CT is a new promising noninvasive method for qualitative and quantitative analysis of tissue-engineering processes.

Simvastatin treatment does not reduce the in vivo degeneration of decellularized heart valve prostheses

Objectives: All present biological heart valve prostheses are prone to progressive in vivo degeneration, which can be partially impaired by decellularization. According to in vitro reports, the administration of statins may provide an additional beneficial effect, whereas clinical trials have failed to prove a positive in vivo result.

Biology of xenogeneic cell and organ transplantation – from bench to bedside – the new German research foundation (DFG) transregio collaborative research centre for the next 4 (ultimately 12) years

Discordant xenotransplantation research started in Hanover/Mariensee and in Munich in the late nineties – the latter receiving a substantial grant from the Bavarian Research Foundation. In 2003 both groups were invited by the German Research Foundation (DFG) to make a joint application to further develop xenotransplantation technology. This was peer‐reviewed, approved and continued with considerable success from 2004 to 2012. The Paul‐Ehrlich and Robert‐Koch Institutes, the official bodies responsible for microbiological safety in Germany, were subsequently included.Our unique interdisciplinary consortium combines basic scientists, animal biotechnologists and clinicians demonstrating an excellent co‐operation over the last 8 years. The tool box available to us includes pigs transgenic for human thrombomodulin, hemoxygenase‐1, A20, LEA 29Y, HLA‐E and TRAIL; key enabling technologies include gene targeting, large transgene vectors, transposon mediated transgenesis, zinc finger and TALE nuclease mediated gene targeting.In July 2012 our new Collaborative Research Centre (again supported by the DFG) commenced, continuing in the first instance to 2016 and ultimately until 2024. The strong Diabetes group at the University of Dresden, which currently runs the only successful allogeneic pancreatic islet transplantation in Germany, has now been incorporated.Our main goal is to translate preclinical studies into benefits for patients as quickly as possible. The consortium focuses on islet, cardiac and renal xenotransplantation; new biological heart valves for paediatric cases and young adults will be developed. Our endeavours will be supported by two ethicists to ensure best practice and promote public dialogue.

Strategies for biological heart valve replacement: Stentless xenografts fail to evolve into an alternative pulmonary valve substitute in a Ross procedure

The Ross operation is a complex procedure for aortic valve replacement in which the pulmonary autograft is replaced by a homograft. However, homograft availability is becoming limited. This report evaluates the performance of porcine stentless prostheses as alternative pulmonary substitutes. Echocardiographic results from two patient cohorts were compared at time of discharge and 1 year after a Ross procedure. Thirty-three patients (median age 42 years, range 17-62 years, 76% male) received a stentless prosthesis (median size 25.6 mm, range 25-29 mm) for right ventricular outflow tract reconstruction. Clinical data were not significantly different from 106 patients (median age 47 years, range 2-68 years, 75% male) who received cryopreserved homografts (median size 26 mm, range 20-33 mm). At time of discharge, peak pressure gradients (ΔPmax ) across the stentless valve (median ΔPmax 13 mmHg, range 2-26 mmHg) were higher compared to homografts (median ΔPmax 7 mmHg, range 1-32 mmHg, p<0.001). At 1 year, gradients increased in both groups, but were significantly higher across stentless valves (median ΔPmax 23 mmHg, range 10-81 mmHg vs. median ΔPmax 13 mmHg, range 2-74 mmHg, p<0.001). Eleven patients (33%) in the stentless-valve group were classified "at risk" with a ΔPmax of ≥30 mmHg. Four of them (12%) had to be re-operated. In conclusion, stentless valves showed higher pressure gradients and their performance was inferior to cryopreserved homografts. See accompanying commentary by Ulrich Stock DOI: 10.1002/biot.201200341.

Transplantation material bovine pericardium: biomechanical and immunogenic characteristics after decellularization vs. glutaraldehyde‐fixing

Today, bovine pericardium (BP) is extensively investigated as a biomaterial for the generation of various bioimplants. But despite the commercial distribution, and the development of methods either to remove (decellularization) or to mask (chemical cross-linking, for example by glutaraldehyde [GA] treatment) the xenogeneic antigen epitopes, yet questions around the immunogenic reactivity of BP remain. The aim of this study is the comparison of crucial tissue characteristics, that is, biomechanical properties, the presence of αGal epitopes, and residual DNA in acellular vs. GA-fixed BP. Bovine pericardium was either cross-linked with 0.6% GA or decellularized according to two common protocols using either sodium dodecyl sulfate (SDS) and desoxycholic acid (DCA) or trypsin and ethylenediaminetetraacetic acid (EDTA). The resulting extracellular matrix was prone to one-dimensional tensile testing. The tissue content for αGal was evaluated by immunoblotting, and residual DNA was determined by a commercial assay. Untreated BP served as control. In contrast to previous reports, we found a pronounced decrease in the elastic modulus (E-Modulus) for common GA treatment and overall smaller values for the elastic moduli after decellularization (P < 0.05). In parallel, we observed an overall increased ultimate elongation of acellular and cross-linked BP, although ultimate stress values did not significantly differ. SDS/DCA decellularized BP revealed a dramatic reduction in the DNA content and an almost complete removal of αGal epitopes, whereas the trypsin/EDTA protocol retained a residual DNA content of almost 50% and with a great trail of αGal signal. GA-treated tissue had a remarkable content of DNA and αGal. Although chemically fixated BP is clinically still in wide use, for example, for biological heart valve engineering, our results suggest that an improved biomaterial preparation may be provided by appropriate decellularization. SDS/DCA decellularized BP shows similar biomechanical characteristics as GA treatment, paired with reduced potential immunogenic reactivity. Furthermore, decellularized BP holds the potential of cellular repopulation in vivo or in vitro, to enable an endogenous regenerative capacity in contrast to the toxic effects of GA fixing.

Development of a transient large strain contact method for biological heart valve simulations

A new 2D method to implement transient contact using Comsol Multiphysics (finite element analysis software that enables multiphysics simulations) is described, which is based on Hertzian contact. This method is compared to the existing (default) contact method that does not enable real transient simulations, but instead performs steady-state solutions where time is a constant. The two types of contact modelling have been applied to simple 2D biological heart valve models, undergoing strains in the region of 10% under 20 kPa pressure (applied over 0.3 s). Both the methods predicted comparable stress patterns, locations of peak stresses, deformations and directions of principal stress. The default contact method predicted slightly greater contact stresses, but spreads over a shorter surface length than the new contact method. The default contact method is useful for contact systems with little transient dependency, due to ease of use. However, where transient conditions are important the new contact method is preferred.

Medical Device Regulatory Landscape

The past 60 years have witnessed fundamental advances in our understanding and treatment of cardiovascular disease, prolonging and improving patients' lives. Central to these improvements has been the introduction of medical devices, including mechanical and biological heart valves, heart rhythm devices, and balloon angioplasty and stents. The introduction of these technologies has been dependent on an entrepreneurial medical device sector, coupled with an equally robust infrastructure to clinically develop and evaluate these new technologies. After approval and commercialization, continued study of device performance under “real world” conditions is crucial to ensure that the clinical potential is being realized. Central to a healthy medial device “ecosystem” is a robust regulatory system. Regulators must ensure that a device performs reliably and is adequately characterized, allowing physicians and patients to use it appropriately. Determining if/when a device is appropriate for approval is difficult and challenging and requires balancing its safety-efficacy profile. The technical sophistication required to make these determinations has grown as device complexity has grown. The stakes are very high, as illustrated by the recent Fidelis AICD lead recall, affecting 268 000 patients worldwide.1 These safety concerns must be balanced by the harm inflicted by withholding beneficial technology from patients. There is wide variation in how devices are regulated among countries with well-developed health care delivery systems, for example, the United States and Europe as well as Japan and Canada. The recent Food and Drug Administration (FDA) approval of the Sapien Transcatheter Heart Valve has brought these differences into sharp focus. In this commentary, we review the differences between the US and European Regulatory systems and how they have affected the investigational and approval process. ### Sapien Transcatheter Heart Valve: A Case Study On November 2, 2011, the Sapien Transcatheter Heart Valve (TAVR), manufactured by Edwards Lifesciences, was approved by the US FDA.2 The approval of the Sapien …

Cardiac imaging of prosthetic valve dysfunction by transesophageal echocardiography

Surgical implantation of a mechanical or biological prosthetic heart valve (PHV) with original structure and hemodynamics is conventional treatment of valvular heart disease. All kinds of prosthetic valves are stenotic comparing with native valves. They should be imagined by being aware of their specific properties. PHV diseases (PHVD) describes situations like obstruction, thromboembolism and regurgitation which also have characteristic images. Determining the cause and severity of PHVD is mandatory for selection of treatment method. Knowledge about PHVD and correct usage of cardiac imaging methods facilitate diagnosis. Most helpful diagnostic test for PHVD is transesophageal echocardiography (TEE). The aim of this review is to describe TEE in PHVD, TEE imaging characteristics of some special PHVD and clinical guidance of TEE in PHV problems.

Nanocoating with titanium reduces iC3b- and granulocyte-activating immune response against glutaraldehyde-fixed bovine pericardium: A new technique to improve biologic heart valve prosthesis durability?

An IgG and granulocyte-activating immune response with secondary dystrophic calcification might be the reason glutaraldehyde (GA)-fixed xenograft valves fail, especially in young patients, who are more immunocompetent than the elderly. Titanium nanocoating on GA-fixed bovine pericardium was tested for its ability to prevent major immunoreactions. The immune activity of platelets from GA-fixed bovine pericardium with different treatment procedures was evaluated using the blood from 5 human donors: group I (n = 5), GA fixed as the control; group 2 (n = 5), detoxified with 10% citric acid; group 3 (n = 5), 10% citric acid, aldehyde-dehydrogenase, and a physical plasma treatment; and group 4 (n = 5), treated the same as group 3, but with an additional titanium coat 30 nm in thickness. Titanium deposition was visualized using scanning electron microscopy. IgG deposits (iC3b) were shown by immunostaining and documented as colored pixels (red). The pixels were evaluated electronically. Attracted granulocytes (polymorphonuclear leukocytes) were counted in front of the titanium-coated surface. IC3b deposits and polymorphonuclear leukocytes within control group 1 were defined as 100%; in group 2, iC3b was 149% ± 34% and polymorphonuclear leukocytes were 89%, in group 3, IC3b was 102% ± 24% and polymorphonuclear leukocytes were 47%; and in group 4, IC3b had decreased to 38.49% ± 21% (P < .05) and polymorphonuclear leukocyte activation had decreased to 6.3% (P ≤ .01). Titanium coating significantly reduced the iC3b and granulocyte activating immune response of GA-fixed pericardium. Therefore, it might prevent relevant immunorejection and increase the durability of GA-fixed bioprosthetic heart valves.

Abstract 17927: Transcatheter Implantation of Autologous in vivo Tissue-Engineered, Valved Stents (BIOVALVED STENTs) in the Pulmonary Position in a Beagle Model

Objectives We developed completely autologous valved conduits (BIOVALVEs) using simple, safe and economical in vivo tissue engineering, which is a practical concept of regenerative medicine. In this study, self-expandable BIOVALVEs impregnating stents (BIOVALVED STENTs) were successfully replaced to pulmonary valves by transcatheter method in a beagle model. The use of BIOVALVED STENTs might solve the problem of degeneration and limited durability of biological heart valves. Methods and Results As a mold for BIOVALVED STENTs preparation, a pair of the custom-designed acrylate rods (diameter, 14 mm; length, 40 mm), assembled with a small aperture in a trileaflet shape, were covered with NiTi stents, and then capped with another pair of acrylate covers at their both terminals. The molds were placed in the dorsal subcutaneous spaces of beagle dogs. After 4 weeks of implantation, autologous connective tissues, impregnating stents, completely covered the surface of the molds and migrated into the apertures for the leaflets. BIOVALVED STENTs with autologous three leaflets, strongly connected with stent strut, were obtained after removing the molds. They had appropriate compliance and robustness (&gt; 3000 mmHg) as the conduit-valves for aortic full root replacement. They were subsequently deployed into the main pulmonary arteries through catheters after technical establishment using allogenic implantation. Postoperative UCG demonstrated smooth movement of the leaflets with little regurgitation for at least up to 3 months. Conclusion Good functioning as the pulmonary valve was observed after implantation of firstly developed BIOVALVED STENTs with completely autologous tissues, which will become a valid future option in adolescents.

Control of an air pressure actuated disposable bioreactor for cultivating heart valves

A disposable injection molded bioreactor for growing tissue-engineered heart valves is controlled to mimic the physiological heart cycle. Tissue-engineered heart valves, cultured from human stem cells, are a possible alternative for replacing failing aortic heart valves, where nowadays biological and mechanical heart valves are used. Growing and conditioning is done by mechanically stimulating the tissue in a bioreactor. The disposable injection molded bioreactor uses flexible membranes and steering valves to mimic a physiological heart cycle. In this work, an air pressure actuation control system for this bioreactor is designed. One membrane is position controlled to achieve a desired flow through the heart valve, while another membrane controls the aortic pressure. A third actuator controls a steering valve used to impose a resistance on the flow back to the first membrane, in order to control the heart valve closing pressure. Due to the repetitive character of the setpoints, repetitive controllers are designed and implemented. A high position tracking performance is achieved and pressure setpoints are mimicked successfully, while preventing large pressure oscillations and suppressing disturbances that could be damaging for the tissue heart valve. The control system allows full adjustability of operating conditions needed for the growing, conditioning and testing phases of tissue engineered heart valves.

Immune Response in Patients Receiving a Bioprosthetic Heart Valve: Lack of Response with Decellularized Valves

Conventional biological heart valves treated with glutaraldehyde (GA) reveal a limited lifespan due to calcification. This is assumed to be an immune response initiated process, which is not seen with decellularized valves. However, their immunological potential is still a matter of debate. Therefore, serum samples from patients undergoing heart valve surgery were obtained before (Pre), after (Post), and 9-12 months after operation (Follow Up). Immunoglobulin G (IgG) and M (IgM) antibodies against porcine collagen I and α-Gal (Gal-alpha1,3-Gal-beta1,4-GlcNac-R) were determined for decellularized and GA treated valves. Antibody titers for collagen type I revealed no significant alteration for both types of valves. However, a considerable anti-α-Gal antibody response was observed in patients with GA-treated porcine valves. In detail, IgM antibodies were increased during follow up (p<0.05), whereas decellularized valves revealed a minor decrease in the IgM response (p<0.001). IgG antibodies were considerably increased with GA-treated porcine (p<0.05) and bovine (p<0.01) xenografts, whereas there was lack of response with decellularized valves. This indicates that GA treatment is not sufficient to eliminate immune response to the α-Gal epitope completely. Future investigations will have to verify whether immune response to α-Gal can be linked to the limited durability of conventional valves.