Angiogenic and inflammatory host response to surgical meshes of different mesh architecture and polymer composition.

One of the major challenges in hernia repair is the development of surgical meshes that guarantee an optimal biocompatibility and incorporation into the host tissue. For this purpose, it is necessary to study the impact of different mesh types on angiogenesis, inflammation, and tissue formation. In the present study, we analyzed the host tissue reaction to Prolene, Ultrapro, and Vicryl meshes over a 14-day period after implantation into the hamster dorsal skinfold chamber using intravital fluorescence microscopy and histology. Our results demonstrate that compared with the Prolene and Ultrapro mesh, the Vicryl mesh induced a more pronounced angiogenic and inflammatory host tissue response with formation of a densely vascularized granulation tissue, which was infiltrated by many inflammatory cells. However, the strong foreign body reaction was not associated with a better mesh incorporation, but resulted in a significantly reduced explantation strength when compared with that of Prolene and Ultrapro meshes. Histological examinations revealed that the granulation tissue surrounding the Vicryl mesh was instable, because of low collagen content and massive infiltration of inflammatory cells. Thus, our data demonstrate that a stronger angiogenic and inflammatory response to an implanted mesh does not necessarily result in a better incorporation into the host tissue.

Rapamycin, but not cyclosporine A, inhibits vascularization and incorporation of implanted surgical meshes.

Incisional hernias are a frequent complication of upper abdominal wall interventions, especially in patients undergoing liver transplantation with subsequent immunosuppressive therapy. Therefore, we analyzed in this study the manner in which the incorporation of a surgical mesh for hernia repair is affected by the immunosuppressant drugs rapamycin and cyclosporine A (CsA). For this purpose, Ultrapro meshes were implanted into the dorsal skinfold chambers of rapamycin- and CsA-treated hamsters. Untreated animals served as controls. The angiogenic and inflammatory host tissue response to the mesh implants was then analyzed over a 14-day period by means of intravital fluorescence microscopy. Mesh incorporation was determined by histology and measurement of explantation strength. Rapamycin dose-dependently inhibited vascularization of implanted meshes, as indicated by a significantly reduced number of angiogenesis-positive regions of interest and microvessel density, when compared with CsA-treated hamsters and controls. In addition, the granulation tissue surrounding the meshes of rapamycin-treated animals exhibited only a low collagen content, resulting in an impaired mesh incorporation with a significantly reduced explantation strength. Leukocyte-endothelial cell interaction did not show marked differences between the observation groups. Thus, immunosuppressed patients should not be treated with rapamycin in case of incisional hernia repair in order to guarantee adequate mesh incorporation.

Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes.

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ.