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Current prosthetic substitutes for heart valves and blood vessels have numerous limitations such as limited durability (biological valves), susceptibility to infection, the necessity of lifelong anticoagulation therapy (prosthetic valves), and reduced patency in small-caliber grafts, for example. Tissue engineering using either polymers or decellularized native allogeneic or xenogenic heart valve/vascular matrices may provide the techniques to develop the ideal heart valve or vascular graft. The matrix scaffold serves as a basis on which seeded cells can organise and develop into the valve or vascular tissue prior to or following implantation. The scaffold is either degraded or metabolised during the formation and organisation of the newly generated matrix, leading to vital living tissue. This paper summarises current research and first clinical developments in the tissue engineering of heart valves and vascular grafts.

The important role of angiogenesis for invasion, tumor growth, metastasis and progression of solid tumors is well established. Only recently, the clinical significance of neovascularization in hematological neoplasms has come into the focus of scientific efforts. Emerging data from these studies suggest that the vascular architecture exerts a pivotal role in acute leukemias and multiple myeloma as well as myeloproliferative disorders. Thus, angiogenesis seems to maintain a general condition for malignant growth and the progression of hematological diseases. However, a major shortcoming is that most of the previous studies include only a simple quantitative evaluation of the microvessel density, and applied methods which were developed primarily for the characterization of angiogenesis in solid tumors. In this context it should not be overlooked that solid neoplasms and the bone marrow reveal significant differences regarding the vascular structures and the distribution of microvessels. Therefore, the usually applied, so-called hot-spot techniques, should be amended by an appropriate and more elaborate computer-assisted morphometric analysis of the microvessel structures. This additional spectrum of information regarding quantity and quality of angiogenesis, enables a further understanding of the morphological changes in the course of diseases, and in particular the effect of various therapies on bone marrow vascularization.

In contrast to articular cartilage the hyaline rib cartilage takes up a special position due to its size, shape and the kind of mechanical stress as well. These facts may influence the metabolism of rib cartilage. In our histological, histochemical and immunohistochemical investigations on pieces of rib cartilages of 34 persons at the age of fourth fetal month up to 60 years we could regularly demonstrate cartilage canals containing blood vessels without any spatial or temporal relationship to degenerative changes in cartilage tissue. Many of these cartilage canals are located in the center of the rib cartilage. Blood vessels as well as neuronal structures in the connective tissue of cartilage canals were detected by means of antibodies against components of the vessel wall (Von Willebrand factor) and nerve fibers (PGP 9.5). Nerves may have sensoric or vasomotoric functions as well, and they may influence cell differentiation and regeneration processes, respectively. Cartilage can not be regarded as vascularized like other tissues, but cartilage canals may have great functional importance for the metabolism of rib cartilage.

From a morphological point of view, too, the summarizing synopsis of the intramural vascular system of the large intestine of mammals shows, that the functional aspect is prominent. As in other studied species the exclusively on the epithelial side existing 'fenestrated endothelium' of the pericryptal and subepithelial capillaries is doubtless the most important structural mark of the large intestinal function, too. Moreover, the direction of the mucosal capillary blood flow informs, that at first the release of the essential substances for the glandular secretion will take place, before epithelial transports concerning the resorption occur. As for the hemodynamic regulatory structures in the wall of the blood-vessels there are obviously differences in their existence depending on the species, respectively they are completely absent such as in the ruminants. Finally, it should be mentioned, that arterio-venous anastomoses could not be detected.

The vascular system of the large intestine of 10 dogs was examined by means of vascular corrosion casts, histology and transmission-electron microscopy. The tela submucosa contains an arterial and a venous vascular plexus. In broader areas of the submucosa, a deep and a superficial vascular plexus, which are interconnected, can be found. The plexus are orientated parallel to the layers of the intestinal wall. On the one hand, these vessels naturally provide self-sufficiency and drainage of the submucosa, and, moreover, direct branches to the stratum circulare of the muscular layer. On the other hand, the submucosal vascular plexus is the 'distributional network' for the functional plexus of the tunica mucosa. The arteries, which ascend to the tunica mucosa, supply a flat arterial network underneath the intestinal glands. Bundles of only a few arteriolae originate from this in order to supply the pericryptal capillaries. In the vicinity of the cryptal orifices, these turn into a network of subepithelial capillaries, which is post-connected to the periglandular capillary plexus. From this 'terminal circulatory pathway', the blood is drained off by veins that enter the submucosal plexus. It is characteristic that the postcapillary venules often begin as part of the capillary network. As in other species, the subepithelial capillaries are pre-dominantly lined with a 'fenestrated endothelium', whereas the capillaries of the pericryptal areas show a continuous endothelium. The latter contains multiple vesicles that may fuse in order to form transcytoplasmic channels as a morphological equivalent for transcappillar-epithelial and vice versa occurring transport of substances.

Decisive for the progression of the arteriosclerosis is the increase of thickness of the intima, as it is shown by histological and morphometrical investigations on the human coronary arteries. A light-optic and electron-optic analysis of animal-experimental, induced and spontaneous proliferations of the intima has the result that the process of progression is maintained by structural and functional variants (modulations) of the myointimal cells. Under the influence of specific and unspecific stimulators they are able to proliferation and migration, abnormal fibre synthesis and lipid storage as well as to phagocytosis and formation of boundary surfaces. Most of the modulations described of the activated muscle cell are temporary adaptations to a changed micromilieu and they are reversible to contractile cells after decrease of the stimulation effect. Therefore it is assumed that in the early stages of the arteriosclerosis a progression phase is to be diagnosed light- and electron-optically essentially at the appearance of proliferation-active and synthesis-active modulations of the smooth muscle cell. An inactive, non-progressive thickening of the intima may be diagnosed by the proof of contractile muscle cells.

On human as well as on animal vascular material a characteristic distribution of activated smooth muscle cells is observed which is characteristic for the course of a lesion. In early stages these cells are above all found below the tunica elastica as well as in the marginal parts of the plaques, whereas later on the distribution is increasingly balanced. These cells are metabolically active and also show a higher division rate. The morphological characteristics of the activated smooth muscle cells are a reference to the metabolic and synthetic activity of the cells. Independent on this a characteristic content of activated smooth muscle cells is revealed during ageing. It is still unclarified in as far prognostic conclusions may be derived from the distribution of this cell form on the human vascular material.

Fractions of extracts of porcine corpora lutea, of bovine brain with fibroblast growth factor activity and whole blood serum versus plasma derived serum were tested using Boyden technique and agarose migration with regard to their influence on the migration behaviour of endothelial cells of calf aortas. All factors showed a concentration dependent stimulation of random migration of the cells. Only whole blood serum versus plasma derived serum had chemotactic activity. Thus it must be supposed that vascularization processes will be only favoured by the first mentioned two factors whereas angiogenesis will be possibly triggered by factors released from blood platelets during blood coagulation.

In culture fibroblasts, endothelial cells and smooth muscle cells from arterial wall are stimulated by thrombin and factor XIII, whereas fibronectin inhibits the proliferation of these cells. Experiments with tumor cells show growth stimulation of sarcoma cells and HeLa cells by thrombin and factor XIII. While growth of sarcoma cells is inhibited by fibronectin, HeLa cells are stimulated by fibronectin in physiological concentrations. Possible mechanisms of these effects and relations to in vivo-phenomena are discussed.