Background/Purpose: The key challenge in tissue engineering is the establishment of an efficient vascularization for tissue constructs guaranteeing long-term survival and function. Vascularization may be achieved by the stimulation of angiogenesis or the inosculation of preformed microvascular networks within the implants to the host microvasculature. The present review provides an overview of these two concepts applied in tissue engineering. Methods: A literature search was performed in PubMed for publications focusing on vascularization, angiogenesis and inosculation in tissue engineering. Results: Several strategies have been proposed to stimulate the ingrowth of new blood vessels into tissue constructs. These include the modification of the chemical composition and architecture of scaffolds, their bioactivation by incorporation of growth factor delivery systems or by cell seeding as well as the stimulation of stem cell recruitment. However, because angiogenesis is a time-consuming process, all of these approaches cannot prevent ischemic cell death within larger 3-dimensional tissue constructs during the initial phase after implantation. To overcome this problem, in vitro or in situ prevascularization has emerged as a novel concept in tissue engineering. This bears the advantage that preformed microvascular networks within tissue constructs simply have to inosculate with the host microvasculature at the implantation site to get completely blood-perfused within a short period of time. Conclusions: During the last years, considerable progress has been made in the development of promising vascularization strategies in tissue engineering. Particularly the inosculation of preformed microvascular networks has the great potential to markedly improve the survival of tissue constructs after implantation. The optimization of this vascularization strategy may pave the way for a broad clinical use of tissue engineering applications in the future.

The implantation of biomaterials into the human body has become an indispensable part of almost all fields of modern medicine. Accordingly, there is an increasing need for appropriate approaches, which can be used to evaluate the suitability of different biomaterials for distinct clinical indications. The dorsal skinfold chamber is a sophisticated experimental model, which has been proven to be extremely valuable for the systematic in vivo analysis of the dynamic interaction of small biomaterial implants with the surrounding host tissue in rats, hamsters and mice. By means of intravital fluorescence microscopy, this chronic model allows for repeated analyses of various cellular, molecular and microvascular mechanisms, which are involved in the early inflammatory and angiogenic host tissue response to biomaterials during the initial 2-3 weeks after implantation. Therefore, the dorsal skinfold chamber has been broadly used during the last two decades to assess the in vivo performance of prosthetic vascular grafts, metallic implants, surgical meshes, bone substitutes, scaffolds for tissue engineering, as well as for locally or systemically applied drug delivery systems. These studies have contributed to identify basic material properties determining the biocompatibility of the implants and vascular ingrowth into their surface or internal structures. Thus, the dorsal skinfold chamber model does not only provide deep insights into the complex interactions of biomaterials with the surrounding soft tissues of the host but also represents an important tool for the future development of novel biomaterials aiming at an optimisation of their biofunctionality in clinical practice.

Angiogenesis, i.e. the development of new blood vessels from pre-existing ones, represents an integral part in the pathogenesis of endometriosis. During the last decade, an increasing number of studies have therefore focused on the anti-angiogenic treatment of the disease. The present review provides a systematic overview of these studies and critically discusses the future role of anti-angiogenic therapy in the multimodal management of endometriosis. Literature searches were performed in PubMed, MEDLINE and ISI Web of Knowledge for original articles published before the end of March 2012, written in the English language and focusing on anti-angiogenic approaches for the therapy of endometriosis. The searches included both animal and human studies. Numerous compounds of different substance groups have been shown to exert anti-angiogenic effects on endometriotic lesions under experimental in vitro and in vivo conditions. These include growth factor inhibitors, endogenous angiogenesis inhibitors, fumagillin analogues, statins, cyclo-oxygenase-2 inhibitors, phytochemical compounds, immunomodulators, dopamine agonists, peroxisome proliferator-activated receptor agonists, progestins, danazol and gonadotropin-releasing hormone (GnRH) agonists. However, clinical evidence for their efficacy in anti-angiogenic endometriosis therapy is still lacking. Anti-angiogenic compounds hold great promise for the future treatment of endometriosis because they may inhibit the establishment of new endometriotic lesions in early stages of the disease or after surgical treatment. Further experimental studies, controlled clinical trials in particular, are required now to clarify which compounds fulfil these expectations without inducing severe side effects in patients with endometriosis.