[Tissue engineering of heart valves]. / Tissue Engineering von Herzklappen.

With the introduction of heart valve prostheses cardiac valvular disease has become much more accessible to therapeutic options. However, currently available prostheses display significant limitations, such as limited long-term durability (biological prostheses) and a long-term necessity for anticoagulation therapy. Hence, alternative prosthesis types have been extensively explored in recent years particularly aiming at the development of vital and regenerative prostheses by means of tissue engineering. In the scientific field, different competing concepts have been introduced, including biological or synthetic scaffolds which can be further enhanced by cellular or extracellular components to promote further in vivo development of the prosthesis after implantation. Nowadays, decellularized donor heart valves are among the most advanced prosthesis types experiencing growing clinical attention and widespread use.

Vacuum-assisted wound closure is superior to primary rewiring in patients with deep sternal wound infection.

OBJECTIVE: Deep sternal wound infections are serious complications after cardiac surgery. The aim of the present study is to compare the outcome after vacuum-assisted wound closure to that after primary rewiring with disinfectant irrigation. The study additionally focuses on defining predictors for the failure of primary rewiring and its impact on postoperative outcome. METHODS: Retrospective analysis was performed in 5232 patients who underwent cardiac surgery with a median sternotomy. 192 patients postoperatively developed deep sternal wound infections and were distributed into 2 therapy groups: a vacuum-assisted wound closure (= VAC) group and a primary rewiring (= RW) group, which was subdivided into healing after rewiring (= RW-h) and failure of rewiring (= RW-f). These groups were compared statistically to reveal coincidental pre-, intra- and postoperative parameters. RESULTS: Compared to the VAC group, the RW group showed a poorer outcome, although RW baseline characteristics were apparently beneficial. Primary rewiring failed in 45.8 % of all cases, which led to even worse outcomes. Important predictors for failure of primary rewiring were morbid obesity, diabetes mellitus type II, chronic obstructive pulmonary disease, preoperatively impaired left ventricular function, postoperatively positive blood and wound cultures, bilateral harvesting of internal thoracic arteries and the need for surgical reexploration. CONCLUSIONS: In spite of patients being in a worse condition, vacuum-assisted wound closure therapy resulted in improved outcomes and thus should be preferred to primary rewiring. Moreover we report on predictors which may indicate whether there is a high risk of rewiring failure.

Heparin-induced thrombocytopenia type II after cardiac surgery: predictors and outcome.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious complication after cardiac surgery. The aim of the present study was to identify pre- and intraoperative predictors for the postoperative occurrence of HIT. The study additionally focused on the impact of HIT on postoperative outcome. METHODS: Retrospective analysis was performed for 5073 patients who had required extracorporeal circulation during cardiac surgery. Patients were divided into 3 groups: 1) patients who had postoperative HIT (HIT+); 2) patients with postoperative thrombocytopenia but without HIT (HIT-); and 3) patients with normal platelet count (C). The groups were statistically compared with regard to pre-, intra- and postoperative parameters. RESULTS: Statistically significant predictors were renal insufficiency, intravenous application of heparin for more than 3 days, previous percutaneous coronary intervention within the last 4 weeks, urgency/emergency operation, combined surgery, prolonged extracorporeal circulation or cross-clamping time, and low cardiac output syndrome. Postoperative HIT was associated with an enhanced risk of renal failure, infectious and thromboembolic complications and in-hospital mortality. CONCLUSION: Postoperative HIT increases morbidity and mortality. The predictors presented in this study can be used to identify patients at risk of developing HIT.

[Tissue engineering: in vitro creation of tissue substitutes]. / Tissue-Engineering ist mehr als nur Gewebezüchtung.

Tissue engineering is a young, multidisciplinary scientific field which aims at generating bioartificial tissues in vitro to restore diseased human organs. This fledgling sector of biosciences emerged few years ago but draws scientific and public attention increasingly, as the recent accomplishments are impressive and promise alternative therapeutic concepts to replace or enhance failing human organs. Tissue engineering using either polymers or decellularized native allogeneic or xenogeneic matrices may provide the techniques to develop the ideal graft. The matrix scaffold can be seeded with cells that organise and develop into tissue prior to or following implantation. This review surveys upon recent developments in the field of in vitro tissue engineering (skin, heart, heart valves, blood vessels, liver, kidney, urogenital, and nerves), without claiming completeness, thus providing an insight into what has been attempted and what may be possible in the near future.

Pulsatile perfusion and cardiomyocyte viability in a solid three-dimensional matrix.

BACKGROUND: The manufacture of full thickness three-dimensional myocardial grafts by means of tissue engineering is limited by the impeded cellular viability in unperfused in vitro systems. We introduce a novel concept of pulsatile tissue culture perfusion to promote ubiquitous cellular viability and metabolism. METHODS: In a novel bioreactor we established pulsatile flow through the embedded three-dimensional tissue culture. Fibrin glue served as the ground matrix wherein neonatal rat cardiomyocytes were inoculated. Fluor-Deoxy-Glucose-Positron-Emission-Tomography (FDG-PET) and life/dead assays were employed for comparative studies of glucose uptake resp. cell viability. RESULTS: A solid 8 mm thick structure resulted. Cellular viability significantly increased in the perfused chambers. We observed centripetal migration of the embedded cardiomyocytes to the site of the core vessel. However, cellular viability was high in the periphery of the tissue block too. FDG-PET revealed enhanced metabolic activity in perfused chambers. CONCLUSIONS: The present concept is highly effective in enhancing cellular viability and metabolism in a three-dimensional tissue culture environment. It could be utilized for various co-culture systems and the generation of viable tissue grafts.

[Ross procedure with combined replacement of the ascending aorta: impact on autograft root function and distensibility]. / Aorta ascendens-Ersatz und Ross-Operation: Einfluss auf die Distensibilität der Neo-Aortenwurzel.

BACKGROUND: The safety and effectiveness of combined aortic root autograft replacement in combination with ascending aorta replacement has been demonstrated recently. Replacement of the ascending aorta with a vascular prosthesis results in an increase in aortic root distension, and aortic root wall stress. In this study we aimed to assess the autograft root dimensions, distensibility, and autograft valve function in patients after Ross operation combined with replacement of the ascending aorta compared to patients who underwent Ross operation only. PATIENTS AND METHODS: Echocardiographic follow-up was performed on 28 patients after Ross operation with complete root replacement only (group R) and 12 patients who received an additional replacement of the ascending aorta (group R/A). The mean follow-up time was 24.9 +/- 17.2 months. Autograft root dimensions, root distensibility and valve function were assessed by echo-cardiography. The aortic root was measured at the level of the annulus, sinus of valsalva, and sinotubular junction. The distensibility was calculated as percent change of radius. RESULTS: The mean distensibility at the annulus level was higher in group R/A (18.4 +/- 6.8% vs 13.4 +/- 8.1%; p = 0.047); at the level of the sinus of valsalva and sinotubular junction no differences were observed. The autograft pressure gradient was within physiological limits in all patients. The majority of patients showed a competent autograft valve (group R: AI 0 degree; 83%, AI I degree; 14%, AI II degree; 3%; group R/A: AI 0 degree; 75%, AI I degree; 25%). CONCLUSIONS: Replacement of the ascending aorta with a non-compliant prosthesis does not effect root dimension, distensibility, and valve function.

Clinically established hemostatic scaffold (tissue fleece) as biomatrix in tissue- and organ-engineering research.

Various types of three-dimensional matrices have been used as basic scaffolds in myocardial tissue engineering. Many of those are limited by insufficient mechanical function, availability, or biocompatibility. We present a clinically established collagen scaffold for the development of bioartificial myocardial tissue. Neonatal rat cardiomyocytes were seeded into Tissue Fleece (Baxter Deutschland, Heidelberg, Germany). Histological and ultrastructural examinations were performed by DAPI and DiOC(18) staining and electron microscopy, respectively. Force measurements from the spontaneously beating construct were obtained. The constructs were stimulated with agents such as adrenalin and calcium, and by stretching. Passive stretch curves were obtained. Spontaneous contractions of solid bioartificial myocardial tissue (BMT), 20 x 15 x 2 mm, resulted. Contractions continued to week 12 (40% of BMTs) in culture. Histology revealed intercellular and also cell-fibril junctions. Elasticity was similar to that of native rat myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. Stretch led to the highest levels of contractile force. In summary, bioartificial myocardial tissue with significant in vitro longevity, spontaneous contractility, and homogeneous cell distribution was produced using Tissue Fleece. Tissue Fleece constitutes an effective scaffold to engineer solid organ structures, which could be used for repair of congenital defects or replacement of diseased tissue.

Carboxyfluorescein diacetate succinimidyl ester facilitates cell tracing and colocalization studies in bioartificial organ engineering.

BACKGROUND: We demonstrate a method that includes colocalization studies to analyze cell suspensions after isolation and to characterize 3-dimensional grafts consisting of cells and matrix in vitro and in vivo. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were labelled by CFDA-SE after harvest. Cells in the isolated cell suspension, the embodied cells in the seeded scaffolds were characterized measuring features such as viability and distribution of the cell types. RESULTS: Selective cell count revealed high yields of viable cardiomyocytes. After seeding cells in collagen matrix, viability of the cells decreased gradually in the time process in vitro. Histology of implanted bioartificial myocardial tissue detected viable cardiomyocytes within the graft. CONCLUSION: Using colocalization histology we could label and track cells within the bioartificial myocardial tissue graft in vitro and post implant and assess viability and distribution.

Traveling after heart transplantation.

BACKGROUND: With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines. METHODS: Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed. RESULTS: Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities. CONCLUSIONS: Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.

In vitro engineering of heart muscle: artificial myocardial tissue.

INTRODUCTION: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. METHODS: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. RESULTS: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca(2+) and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. CONCLUSIONS: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.