Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.

INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.

Moderate and severe periodontitis are independent risk factors associated with low cardiorespiratory fitness in sedentary non-smoking men aged between 45 and 65 years.

AIM: To investigate the association between periodontal disease severity and cardiorespiratory fitness (CRF) in a cross-sectional study of sedentary men. MATERIALS & METHODS: Seventy-two healthy men (45-65 years) who did not join any sport activity and had a preferentially sitting working position were recruited. Periodontal status was recorded and CRF was measured by peak oxygen uptake (VO2 peak ) during exercise testing on a cycle ergometer. Physical activity was assessed by a validated questionnaire and data were transformed to metabolic equivalent of task scores. Univariate and multivariate regression analyses were performed to investigate associations. RESULTS: Differences between VO2 peak levels in subjects with no or mild, moderate or severe periodontitis were statistically significant (p = 0.026). Individuals with low VO2 peak values showed high BMI scores, high concentrations of high-sensitive C-reactive protein, low levels of high-density lipoprotein-cholesterol, and used more glucocorticoids compared to individuals with high VO2 peak levels. Multivariate regression analysis showed that high age (p = 0.090), high BMI scores (p < 0.001), low levels of physical activity (p = 0.031) and moderate (p = 0.087), respectively, severe periodontitis (p = 0.033) were significantly associated with low VO2 peak levels. CONCLUSIONS: This study demonstrated that moderate and severe periodontitis were independently associated with low levels of CRF in sedentary men aged between 45 and 65 years.

Prevention of early vascular graft infection using regional antibiotic release.

BACKGROUND: Infections after prosthetic replacement of the aorta remain a serious and life-threatening complication. The only appropriate treatment is the surgical removal of the infected prosthesis. Accordingly, there is a need for new procedures to prevent the infection of vascular prostheses. This in vitro experiment investigated the effect of the pretreatment of vascular prostheses with antibiotics (daptomycin or baneocin) and the effect of antibiotics combined with fibrin sealant as possible prophylaxis of perioperative graft infection. METHODS: Untreated prostheses served as controls. Pretreated prostheses of double woven velour vascular grafts were contaminated with Staphylococcus epidermidis, and colony-forming units were counted each day (CFU/mL). RESULTS: The period of sterility differed significantly as a function of the pretreatment. Uncoated prostheses were immediately non-sterile and exhibited 2.63 ± 0.61 × 10(5) CFU/mL. Baneocin pretreatment resulted in sterility for 1.7 ± 0.6 (95% confidence interval (CI) 1.0-2.4) d before we detected 2.14 ± 0.57 × 10(5) CFU/mL on the prostheses. Pretreatment with daptomycin yielded 2.9 ± 0.4 (CI 2.6-3.2) and fibrin sealant/baneocin compound yielded 3.1 ± 0.3 (CI 2.9-3.3) d of sterility, after which 1.81 ± 0.86 × 10(5) CFU/mL and 1.04 ± 0.77 × 10(5) CFU/mL were recorded. Finally, pretreatment with fibrin sealant/daptomycin led to sterility for 7.1 ± 0.3 (CI 6.9-7.3) d, after which 0.77 ± 0.60 × 10(5) CFU/mL were observed on the prostheses. CONCLUSIONS: The risk of vascular graft infection is reduced by pretreating the prostheses with antibiotics. The antibiotic/fibrin compound exhibited an effect of delayed antibiotic release. Vascular prostheses should therefore be pretreated with antibiotic solution to reduce bacterial adhesion. This procedure might be an effective prophylaxis for perioperative vascular graft infection and provides suitable protection for the prosthetic material.

Biological scaffolds for heart valve tissue engineering.

Tissue engineering might bear promising solutions for overcoming the limitations of biological and mechanical heart valve substitutes. The concept of heart valve tissue engineering bases on decellularized biological matrices, as removal of cellular components might reduce immunological reactions, which are thought to be responsible for accelerated valvular graft deterioration and their subsequent repopulation with autologous cells, which leads to tissue integrity and continuous remodeling. Here, we report a method for efficient removal of cells from ovine heart valve tissue (including cusp, wall, and myocardial cuff) by detergents for the generation of biological valvular scaffolds.

Tracheal cartilage - evaluating the potential of a novel biomaterial for reconstructive cardiovascular procedures.

Modern cardiovascular medicine aims for procedures that preferably involve biological materials and, ideally, living implants. Thereby, the regenerative capacity of the target organ may be preserved or even supported, with a potential implant growth capacity during the following time. In the current study we sought to evaluate the integrative capacity of vital and non-vital tracheal cartilage rings (TCRs) of allogenic or xenogenic origin (allo-/xeno-vTCR; allo-/xeno-nvTCR) as biomaterials under the in vivo functional load of the circulatory system. Ovine and porcine vTCRs and nvTCRs were implanted in the mitral valve (MV) position for 3 and 9 months (n = 3 each), respectively, in lambs. MV function and TCR position were analysed by echocardiography. Tissue morphology (planimetry), vitality (live/dead-assay) and implant endothelialization (scanning electron microscopy) were analysed. No functional impairment or significant MV insufficiency or stenosis was observed in any group. TCR shrinkage was observed in all xeno-TCRs and allo-nvTCRs at 3 months. Only TCRs of allogenic groups at 9 months and allo-vTCRs at 3 months showed a ring area comparable to its size at implantation. Moreover, allogenic vital cartilage showed superior tissue integration, greater endothelialization, less inflammation and calcification. Interestingly, in this group viable cartilage cells were found up to 9 months after implantation. Allogenic viable cartilage may represent a well-suited living material for reconstructive cardiovascular procedures, and further studies are warranted to elucidate the benefits of this novel material, particularly as a structurally supportive component in growing recipients.

In vivo degradation of magnesium alloy LA63 scaffolds for temporary stabilization of biological myocardial grafts in a swine model.

Synthetic or biological patch materials used for surgical myocardial reconstruction are often fragile. Therefore, a transient support by degradable magnesium scaffolds can reduce the risk of dilation or rupture of the patch until physiological remodeling has led to a sufficient mechanical durability. However, there is evidence that magnesium implants can influence the growth and physiological behavior of the host's cells and tissue. Hence, we epicardially implanted scaffolds of the magnesium fluoride-coated magnesium alloy LA63 in a swine model to assess biocompatibility and degradation kinetics. Chemical analysis of the pigs' organs revealed no toxic accumulation of magnesium ions in the skeletal muscle, myocardium, liver, kidney, and bone of the pigs 1, 3, and 6 months postimplantation. The implants were surrounded by a fibrous granulation tissue, but no signs of necrosis were histologically evaluable. A sufficiently slow degradation rate of the magnesium alloy scaffold can be demonstrated via micro-computed tomography investigation. We conclude that stabilizing scaffolds of the magnesium fluoride-coated magnesium alloy LA63 can be used for epicardial application because no significant adverse effects to myocardial tissue were noted. Thus, degradable stabilizing scaffolds of this magnesium alloy with a slow degradation rate can extend the indication of innovative biological and synthetic patch materials.

Reduced thrombocyte adhesion to endothelialized poly 4-methyl-1-pentene gas exchange membranes­a first step toward bioartificial lung development.

Polymeric materials used in biomedical devices, bioartificial organs, or for the fabrication of tissue engineering scaffolds should completely prevent the activation of the coagulation system and subsequent clot formation. Surface endothelialization is considered an important tool to optimize the blood compatibility of synthetic materials, as a functional endothelial cell layer on an artificial material may help control hemostasis and, therefore, provide a solution to improve the biocompatibility of these materials. Here we report on the endothelialization of poly 4-methyl-1-pentene (PMP) gas exchange membranes using human cord blood-derived late outgrowth endothelial colony forming cells. We achieved complete endothelialization of PMP membranes; and when seeded and cultivated on the membrane, cord blood-derived late outgrowth endothelial colony forming cells maintained both endothelial characteristics and functionality. Endothelialization resulted in significantly lower platelet adhesion and activation compared with unseeded membranes. Of importance, the endothelial layer had no major impact on gas permeability of PMP membranes. This study is a first promising step toward the development of a biofunctionalized surface for the use in gas exchange devices with blood contacting surfaces and a straightforward approach toward a long-term bio-hybrid lung replacement system.