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Origin and appearance of HITS induced by prosthetic heart valves: an in vitro study.

Patients with mechanical heart valve prostheses show significantly enhanced numbers of HITS detected by transcranial Doppler ultrasound. In order to assess the origin of HITS formation, an in vitro study was set out to quantify valve induced microemboli for mechanical and bioprosthetic valves under various circulatory conditions by means of Ultrasound-Doppler-Sonography. At the same time the influence of CO2 partial pressure on HITS rate vas investigated. It can be summarised that for mechanical heart valve prostheses a strong correlation exists between left ventricular dp/dtmax and the detected HITS rates. It was also demonstrated that a bioprosthesis generates significantly less HITS than a mechanical valve. The origin of HITS is gaseous since the tests were carried out using a cell-free filtered water-glycerol test fluid. The HITS rate could be increased by increasing the amount of dissolved gas within the test fluid. The results support the hypothesis that cavitation is the key factor in the appearance of gaseous microemboli at heart valve prostheses.

Heart Valve Prosthesis↗

Clinical application of tissue engineered human heart valves using autologous progenitor cells.

BACKGROUND: Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. METHODS AND RESULTS: Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. CONCLUSIONS: TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.

Adolescent↗

Choosing a prosthetic heart valve.

Although most of the available prosthetic heart valves function remarkably well, the variety of available choices attests to the inability of any single one to fulfill the requirements of the ideal valve substitute. The mechanical prostheses include the caged-ball, tilting-disc, and bileaflet valves. Tissue valves available in the United States are the Carpentier-Edwards and Hancock porcine heterograft valves and the Carpentier-Edwards pericardial valve. Review of several large comparative studies on valve performance reveals that the overall results with tissue and mechanical valves are about equal at the end of 10 years. The characteristics of each type of valve substitute dictate the selection of one prosthesis in preference to others for a particular patient. Mechanical prostheses are recommended for patients without contraindications for anticoagulants. Tissue valves are reserved for patients over 65 years of age or for patients in whom anticoagulation is contraindicated. Multiple other patient-related factors need to be considered in selecting the appropriate valve, including the psychosocial situation and patient preference.

Biocompatible Materials↗

Effect of the sinus of valsalva on the closing motion of bileaflet prosthetic heart valves.

Conventional bileaflet prosthetic mechanical heart valves close passively with backflow. Naturally, the valve has problems associated with closure, such as backflow, water hammer effect, and fracture of the leaflet. On the other hand, in the case of the natural aortic valve, the vortex flow in the sinus of Valsalva pushes the leaflet to close, and the valve starts the closing motion earlier than the prosthetic valve as the forward flow decelerates. This closing mechanism is thought to decrease backflow at valve closure. In this study, we propose a new bileaflet mechanical valve resembling a drawbridge in shape, and the prototype valve was designed so that the leaflet closes with the help of the vortex flow in the sinus. The test valve was made of aluminum alloy, and its closing motion was compared to that of the CarboMedics (CM) valve. Both valves were driven by a computer controlled hydraulic mock circulator and were photographed at 648 frames/s by a high speed charge-coupled device (CCD) camera. Each frame of the valve motion image was analyzed with a personal computer, and the opening angles were measured. The flow rate was set as 5.0 L/min. The system was pulsed with 70 bpm, and the systolic/diastolic ratio was 0.3. Glycerin water was used as the circulation fluid at room temperature, and polystyrene particles were used to visualize the streamline. The model of the sinus of Valsalva was made of transparent silicone rubber. As a result, high speed video analysis showed that the test valve started the closing motion 41 ms earlier than the CM valve, and streamline analysis showed that the test valve had a closing mechanism similar to the natural one with the effect of vortex flow. The structure of the test valve was thought to be effective for soft closure and could solve problems associated with closure.

Alloys↗

Autologous human tissue-engineered heart valves: prospects for systemic application.

BACKGROUND: Tissue engineering represents a promising approach for the development of living heart valve replacements. In vivo animal studies of tissue-engineered autologous heart valves have focused on pulmonary valve replacements, leaving the challenge to tissue engineer heart valves suitable for systemic application using human cells. METHODS AND RESULTS: Tissue-engineered human heart valves were analyzed up to 4 weeks and conditioning using bioreactors was compared with static culturing. Tissue formation and mechanical properties increased with time and when using conditioning. Organization of the tissue, in terms of anisotropic properties, increased when conditioning was dynamic in nature. Exposure of the valves to physiological aortic valve flow demonstrated proper opening motion. Closure dynamics were suboptimal, most likely caused by the lower degree of anisotropy when compared with native aortic valve leaflets. CONCLUSIONS: This study presents autologous tissue-engineered heart valves based on human saphenous vein cells and a rapid degrading synthetic scaffold. Tissue properties and mechanical behavior might allow for use as living aortic valve replacements.

Absorbable Implants↗

Selecting the best heart valve for your patient: mechanical or tissue.

This review provides general guidance for heart valve selection. Mechanical heart valves exhibit excellent durability and hemodynamic performance but require anticoagulation to reduce thromboembolism, and therefore risk of anticoagulation-related hemorrhage is increased. Tissue valves were introduced to avoid anticoagulation, but in fact often do not, and lack durability. A literature review was performed to compare the complications of thromboembolism, anticoagulation-related hemorrhage, reoperation structural valve deterioration, and reoperative mortality associated with mechanical and tissue valves. The thromboembolism rates for mechanical and tissue valves are equivalent. During their lives, many recipients of tissue valves receive anticoagulation therapy due to comorbid conditions. The anticoagulation-related blood loss rates associated with mitral mechanical valves and mitral tissue valves are equivalent, whereas the blood loss rates associated with aortic tissue valves are less than those associated with aortic mechanical valves.

Anticoagulants↗

Congenital blood cysts of the heart valves.

Congenital blood cysts of the heart valves are found most commonly on the tricuspid and mitral valves of fetuses and infants. Hearts available following 38 random autopsies of fetuses and infants 2 years of age or younger were examined. Blood cysts were found in 18 cases (47 per cent) in which ages ranged from 26 weeks of gestation to 11 months. The cysts varied in diameter, from microscopic to 3 mm. Affected valves had from one to 20 cysts. Light microscopic examination of serially sectioned paraffin-embedded tissue and plastic-embedded tissue and scanning electron microscopic examination revealed connections between the cyst lumens and ventricles via small endothelium-lined channels. The cyst structure suggested formation from ventricular endothelial infoldings in the valve leaflet base, which bulged into the atrium because of the pressure gradient present during valve closure. Blood cysts are a common finding in neonates dying of various causes and probably have no clinical significance. There is no association with asphyxia as previously described. Blood cysts may persist and enlarge to form giant cysts of the heart valves.

Aortic Valve↗

Computation of wear in artificial heart valves.

In order to assist with the prognosis of wear processes in low profile disc heart valves, an approximate haemodynamic theory has been used for the determination of opening and closing dynamics of these valves, together with the most developed theory to date of frictional fatigue. The heart valve element wear was defined by solving the contact problem, which takes account of changes to the contact surface form as a consequence of wear. Calculated values are compared with in vivo wear data for artificial heart valves. The proposed model for estimating wear in artificial heart valves allows an optimization to be made of the wear resistance in available designs and to predict the wear resistance of artificial heart valves at the design stage.

Biomechanical Phenomena↗

Time-related risk of the St. Jude Silzone heart valve.

OBJECTIVE: The St. Jude Medical Silzone heart valve had a silver-impregnated sewing ring designed to reduce the incidence of prosthetic valve endocarditis. Recruitment to the randomized AVERT study comparing Silzone valves with non-Silzone Control valves was stopped because of an increased risk of reoperation for paravalvular leak, but patient follow-up continues. Determining the time-related risk profile of the Silzone valve is important for helping physicians manage the approximately 28,000 patients currently alive with a Silzone valve. METHODS: Between 1998 and 2000, 403 Silzone and 404 Control patients were enrolled in AVERT. As of July 2005, there were 1819 Silzone and 1842 Control patient-years of follow-up (mean 4.5, median 5.1 years). Analysis emphasized the use and interpretation of hazard functions, since they are more meaningful than event-free percentages to currently surviving patients. To this end, instead of Cox regression, which estimates the hazard ratio, assuming it is constant over time, we employed primarily Aalen additive regression, which measures the hazard difference, and produces a plot of it over time. We assessed the risks of major paravalvular leak, endocarditis, bleeding and thrombo-embolism. RESULTS: The Silzone valve had a higher initial risk of major paravalvular leak than Control in the mitral (p=0.02) position, but not in the aortic (p=0.42) position. Analysis of this risk using additive regression, with all valve positions combined, showed that the initial risk due to Silzone lost statistical significance by 2 years and disappeared by 4 years after implant. In the mitral position, the Silzone valve had a higher initial risk of thrombo-embolism plus bleeding than Control; this risk also lost statistical significance by 2 years and subsided to zero by 4 years. The risks for death and endocarditis were similar for Slizone and Control valves. CONCLUSIONS: The additional risks of the Silzone valve, compared to Control, diminish over time and disappear by 4 years after implant. The minimum time after implant of the patients currently alive with Silzone is now well beyond 5 years; thus, these current patients now have a risk profile similar to that of patients with a standard St. Jude valve.

Aged↗

Definitive cure of recurrent prosthetic endocarditis using silver-coated St. Jude Medical heart valves: a preliminary case report.

Despite progress in the area of antimicrobial treatment and the surgical use of homografts, prosthetic valve endocarditis (PVE) remains one of the most dangerous complications following heart valve replacement. We present the case of a patient treated for acute endocarditis which affected the mitral valve and who developed recurrent PVE and native aortic valve endocarditis. After multiple valve surgery, the infection was controlled following aortic and mitral valve replacement using silver-coated prostheses. The St. Jude Medical (SJM) mechanical heart valve Masters Series with Silzone coating is intended to protect heart valve patients against microbial infection. The Silzone coating is formed by an ion beam-assisted deposition process that incorporates silver into the sewing cuff of the SJM heart valve. It has also been suggested that silver treatment may improve the healing characteristics of the heart valve sewing cuff. This technology may be a valuable option to prevent or cure PVE, in addition to homografts. Although the present patient is an isolated case, it was encouraging to find not only a well-healed mitral valve silver-coated prosthesis but also no persistent or recurrent infection during a nine-month follow up.

Adult↗

Diagnostic value of intraoperative swabs of heart valves in infective endocarditis.

BACKGROUND AND AIM OF THE STUDY: Intraoperative swabs of heart valves are obtained regularly from patients undergoing heart valve surgery for infective endocarditis (IE) in order to confirm the preoperative diagnosis and to adjust the antibiotic regimen. The study aim was to assess the diagnostic value of intraoperative swabs of heart valves in IE. METHODS: A total of 83 patients was referred for surgical treatment of active IE between October 1994 and May 1999. Preoperatively, microorganisms were isolated using a minimum of two positive blood cultures; results were compared with those obtained from intraoperative heart valve swab cultures. RESULTS: Preoperatively, 73 patients (88%) had a positive blood culture, and 10 (12%) had culture-negative endocarditis. The intraoperative swab confirmed the preoperative diagnosis in 31 cases (37%). Bacteria were isolated in three of the ten patients with preoperative culture-negative IE. Despite positive histopathological findings in seven patients, no microorganisms were cultured either pre- or intraoperatively. Among the remaining 42 patients (51%) with active IE, 25 valve cultures were sterile and 17 valve swabs were presumed to be contaminated. CONCLUSION: In patients with active IE in whom the causative agent could be isolated and identified before surgery, intraoperative valve swabs did not contribute further to patient management. In isolating contaminants, the risk of inappropriate modification of the antibiotic regimen is imminent. The diagnostic validity in culture-negative IE appears negligible.

Adolescent↗

Fifteen years' clinical experience with the CarboMedics prosthetic heart valve.

BACKGROUND AND AIM OF THE STUDY: The CarboMedics bileaflet prosthetic heart valve was first implanted as part of a prospective clinical study at the authors' institution in November 1987. The patient cohort included was part of a multicenter trial set up by the manufacturer for an FDA application. The present report details findings over a 15-year period, with a continuous follow up on this patient cohort. METHODS: Between November 1987 and August 1990, 132 patients (68 males, 64 females; median age 56 years; range: 12-74 years) received a CarboMedics heart valve prosthesis. All patients were included in the study, whether surgery was elective or emergency, first time or reoperation. There were 69 aortic, 49 mitral and 12 double (aortic and mitral) valve replacements. Two patients had isolated tricuspid valve replacement. Concomitant surgery was performed in 15 patients. Anticoagulation with warfarin was started on postoperative day 1. After discharge, patients were examined regularly as outpatients for up to five years. Subsequent follow up was obtained prospectively by questionnaires to the patients' general practitioners and with telephone calls to the patients. Actuarial estimates of survival and freedom from morbid events were calculated using the Kaplan-Meier method; 95% confidence limits for the distribution function were calculated according to the Greenwood formula. RESULTS: Complete follow up information was available on 94% of the patients; total follow up was 1,270.3 patient-years (pt-yr). Actuarial survival at 15 years was 51+/-4.9% overall; 56+/-6.2% for single aortic, 51+/-8.0% for single mitral, and 30+/-15.9% for double valve replacements. Actuarial rates of freedom from complications were: valve thrombosis 100%, embolism 89+/-3.3%, and all anticoagulant-related bleeding 76+/-4.5%. The linearized rates per 100 pt-yr were: embolism 0.94 (aortic 0.74, mitral 1.25); anticoagulant-related bleeding 2.28; paravalvular leakage overall 0.24 (aortic 0.29); prosthetic valve endocarditis overall 0.24 (aortic 0.29, mitral 0.21). There was no hemolysis, prosthetic valve dysfunction, or structural deterioration. CONCLUSION: Over a 15-year time frame, the CarboMedics prosthetic heart valve has proven to be a highly reliable device with no structural failures and a low incidence of valve-related complications.

Adolescent↗

Laboratory evaluation of tissue heart valves. A comparative assessment.

Tissue of commercially prepared tissue heart valves were evaluated and compared with aluminium treated, fixed porcine valve tissue in vitro (tensile strength, scanning and transmission electron microscopy) and in vivo (calcification potential after subcutaneous implantation in the rat model). Valve leaflets (n = 40) were divided into four groups according to the method of treatment: Group I (fixed in 0.652% glutaraldehyde, control), Group II (fixed and treated with aluminium), Group III (fixed and treated with Toluidine blue) and Group IV (fixed and treated with watersoluble alkyl sulphate). Tensile strength was not influenced in Group II and III (p > 0.05). Group IV indicated a significant (p < 0.05) reduction in tensile strength. Scanning electron microscopy revealed damage and loss of surface endothelium in Group III and IV respectively. Transmission electron microscopy indicated damage to underlying matricial cells in Group III and IV. Calcification potential was significantly (p < 0.001) reduced in Group II to IV. We conclude that damage ultrastructure could contribute to the reduced tensile strength in Group IV and that reduced tensile strength might have an influence on the long-term durability of tissue heart valves. Antimineralization treatment of tissue heart valves does retard calcification but is yet unable to inhibit the process completely.

Animals↗

Perioperative anticoagulation for patients with mechanical heart valves: a survey of current practice.

BACKGROUND: Patients with mechanical heart valves (MHV) require temporary interruption of warfarin when undergoing invasive procedures. Current guidelines addressing this subject are discordant because there is no high quality evidence to support any single management strategy. We tested the hypothesis that there is significant practice variation amongst clinicians caring for patients with MHV who require temporary cessation of their warfarin therapy. METHODS: A survey describing 4 hypothetical patients with mechanical heart valves was distributed to all clinicians attending an anticoagulation specialty meeting. For each scenario, the attendee was given several choices for preoperative and postoperative anticoagulation management. Information about each respondent's profession, specialty and the frequency with which they make perioperative anticoagulation recommendations was also collected. RESULTS: Three hundred twenty-four of 650 surveys were returned. In each of the case scenarios, a majority of respondents selected subcutaneous low molecular weight heparin (LMWH) or subcutaneous unfractionated heparin (UH) as the preferred pre- and postoperative anticoagulant. Significant variation in practice was noted: for none of the questions was a single strategy selected by greater than 80% of respondents. CONCLUSION: Expert clinicians differ in their perioperative management strategies for patients with MHV who require interruption of warfarin. Although subcutaneous LMWH/UH was the treatment of choice in all scenarios, the lack of consensus found in our survey highlights the need for randomized controlled clinical trials of peri-procedural anticoagulant therapy. This survey of anticoagulation experts reveals that there is significant practice variation in scenarios where temporary interruption of warfarin is necessary in patients with mechanical heart valves. Despite discordant guidelines and a lack of high-quality data to support any strategy, a majority of the respondents surveyed would use low molecular weight heparin (or subcutaneous unfractionated heparin) to anticoagulate patients with mechanical heart valves during the peri-operative period.

Anticoagulants↗

Explanted cryopreserved allografts: a morphological and immunohistochemical comparison between arterial allografts and allograft heart valves from infants and adults.

OBJECTIVE: Life expectancy of cryopreserved allografts implanted in infants is different from those implanted in adults. A morphological study of explanted allograft heart valves was performed to determine the mechanism of deterioration and to compare cryopreserved arterial and heart valve allografts from adult patients with those explanted from infants. METHOD: Between 1987 and 1996, 209 cryopreserved allografts were implanted: 125 valved conduits or monocusps to reconstruct the right ventricular outflow tract in congenital heart disease, 50 allograft heart valves to treat native aortic and prosthetic aortic valve endocarditis and 34 cryopreserved arterial allografts to replace mycotic aortic aneurysms or infected aortic prosthetic grafts. Two months to 8 years after implantation, 23 heart valve allografts, 11 right-sided and 12 left-sided, and four arterial allografts had to be explanted for reasons such as degeneration, recurrent infection, aneurysm formation or rupture. Besides conventional staining, immunohistochemical detection of cell populations was performed as follows: CD45RO, CD3 and CD43 for T lymphocytes, CD20 for B lymphocytes, CD68 for macrophages, protein S100 for Langerhans-cells, vimentin for fibroblasts, alpha-actin for smooth muscle cells and factor VIII for endothelial cells. RESULTS: Explanted cryopreserved allografts were all fibrotic, acellular, non-vital and without endothelial cells. The fibrous tissue was preserved. T lymphocytes, indicating rejection, were found in all right-sided allografts from the paediatric population, but only in 9% of left-sided valves explanted from adults and in one of the four of arterial allografts. Macrophages and Langerhans-cells were found only in right-sided allografts from paediatric patients. CONCLUSION: Right-sided cryopreserved allografts from a paediatric population showed ongoing cellular rejection. By contrast, there was only a weak T-cell mediated rejection to adult heart valve and arterial allografts. Therefore, similar long-term results can be expected in adult arterial and heart valve allografts, whereas longevity of right-sided heart valve allograft in the paediatric age group seems endangered by cellular rejection.

Adolescent↗

Drug treatment associated with heart valve replacement.

This article reviews a number of specific pharmacological considerations for patients with prosthetic heart valves. All patients with mechanical heart valves should be anticoagulated. In the past, an International Normalised Ratio (INR) of 2.5 to 4.5 has been recommended. Recent nonrandomised studies have suggested that a patient with a prosthetic valve who is at low risk for thromboembolic events could have an INR ranging from 1.8 to 3.5. The lower end of this range should only be used for patients at higher than average risk of haemorrhage, until randomised data show that levels below 2.5 may be applied universally. In high-risk patients (particularly those with previous thromboembolic events) low dose aspirin should be added. During noncardiac surgery, a patient at low risk for thromboembolic events could be managed by discontinuing anticoagulation 3 days before the operation, with warfarin recommenced as soon as possible afterwards. Perioperative heparinisation would be appropriate in a higher risk patient. Women with prosthetic heart valves wishing to become pregnant should be converted to the use of twice-daily subcutaneous heparin injections. Patients with bioprosthetic valves can be managed without anticoagulation unless they have some other reason to require it. Patients at high risk should be treated with aspirin or warfarin. Thrombolytic therapy for acute valve thrombosis should be used for those who are haemodynamically compromised and therefore have a high risk of mortality from operative intervention. All patients with prosthetic heart valves undergoing invasive procedures potentially causing bacteraemia should receive antibiotic prophylaxis for endocarditis. The actual drugs used depend on the likely nature of the bacteraemia, and any possible patient hypersensitivity.

Anti-Bacterial Agents↗

Twelve years' clinical experience with the CarboMedics prosthetic heart valve.

BACKGROUND AND AIM OF THE STUDY: The CarboMedics bileaflet prosthetic heart valve was first implanted as part of a prospective clinical study at the authors' institution in November 1987. The patient cohort included was part of a multicenter trial set up by the manufacturer for an FDA application. The present report details findings over a 12-year period, with a continuous follow up on this patient cohort. METHODS: Between November 1987 and August 1990, 132 patients (68 males, 64 females; median age 56 years; range 12-74 years) received a CarboMedics heart valve prosthesis. All patients were included in the study, whether surgery was elective or emergency, first time or reoperation. There were 69 aortic, 49 mitral and 12 double (aortic + mitral) valve replacements. Two patients had isolated tricuspid valve replacement. Concomitant surgery was performed in 15 patients. Anticoagulation with warfarin was started on postoperative day 1. After discharge, patients were examined regularly as outpatients for up to five years. Subsequent follow up was obtained prospectively by questionnaires to the patients' general practitioner, or by telephone calls. Actuarial estimates of survival and freedom from morbid events were calculated using the Kaplan-Meier method; 95% confidence limits for the distribution function were calculated according to the Greenwood formula. RESULTS: Complete follow up information was available for 94% of the patients; total follow up was 1,014.3 patient-years (pt-yr). Actuarial survival at 12 years was 62 +/- 0.5% overall (61 +/- 6.5% for aortic; 66 +/- 7.5% for mitral; 65 +/- 14.0% for double valve replacements). Actuarial rates of freedom from complications were: valve thrombosis 100%, embolism 92 +/- 2.8%, and anticoagulant-related bleeding 77 +/- 5.6%. The linearized rates per 100 pt-yr were: embolism 0.89 (aortic 0.74, mitral 1.30); anticoagulant-related bleeding 2.56; paravalvular leakage overall 0.20 (aortic 0.37); prosthetic valve endocarditis overall 0.20 (aortic 0.37). There was no hemolysis, prosthetic valve dysfunction or structural deterioration. CONCLUSION: Over a 12-year time frame, the CarboMedics prosthetic heart valve has proven to be a highly reliable device with no structural failures, and a low incidence of valve-related complications.

Adolescent↗

The relevance of large strains in functional tissue engineering of heart valves.

BACKGROUND: Exposing the developing tissue to flow and pressure in a bioreactor has been shown to enhance tissue formation in tissue-engineered heart valves. Animal studies showed excellent functionality in these valves in the pulmonary position. However, they lack the mechanical strength for implantation in the high-pressure aortic position. Improving the in vitro conditioning protocol is an important step towards the use of these valves as aortic heart valve replacements. In this study, the relevance of large strains to improve the mechanical conditioning protocol was investigated. METHODS: Using a newly developed device, engineered heart valve tissue was exposed to increasing cyclic strain in vitro. Tissue formation and mechanical properties were analyzed and compared to unstrained controls. RESULTS: Straining resulted in more pronounced and organized tissue formation with superior mechanical properties over unstrained controls. Overall tissue properties improved with increasing strain levels. CONCLUSIONS: The results demonstrate the significance of large strains in promoting tissue formation. This study may provide a methodological basis for tissue engineering of heart valves appropriate for systemic pressure applications.

Absorbable Implants↗