It is well known that the number of patients requiring a vascular grafts for use as vessel replacement in cardiovascular diseases, or as vascular access site for hemodialysis is ever increasing. The development of tissue engineered blood vessels (TEBV’s) is a promising method to meet this increasing demand vascular grafts, without having to rely on poorly performing synthetic options such as polytetrafluoroethylene (PTFE) or Dacron. The generation of in vivo TEBV’s involves utilizing the host reaction to an implanted biomaterial for the generation of completely autologous tissues. Essentially this approach to the development of TEBV’s makes use of the foreign body response to biomaterials for the construction of the entire vascular replacement tissue within the patient’s own body. In this review we will discuss the method of developing in vivo TEBV’s, and debate the approaches of several research groups that have implemented this method.

Vascular access is the lifeline for patients on hemodialysis. Arteriovenous fistulas (AVFs) are the preferred vascular access, but AVF maturation failure remains a significant clinical problem. Currently, there are no effective therapies available to prevent or treat AVF maturation failure. AVF maturation failure frequently results from venous stenosis at the AVF anastomosis, which is secondary to poor outward vascular remodeling and excessive venous intimal hyperplasia that narrows the AVF lumen. Arteriovenous grafts (AVGs) are the next preferred vascular access when an AVF creation is not possible. AVG failure is primarily the result of venous stenosis at the vein-graft anastomosis, which originates from intimal hyperplasia development. Although there has been advancement in our knowledge of the pathophysiology of AVF maturation and AVG failure, this has not translated into effective therapies for these two important clinical problems. Further work will be required to dissect out the mechanisms of AVF maturation failure and AVG failure to develop more specific therapies. This review highlights the major recent advancements in AVF and AVG biology, reviews major clinical trials, and discusses new areas for future research.

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The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation. In the present study, we evaluated the consequences of RXFP1 knockout ( Rxfp1) on AVF maturation in a murine model of AVF failure. Rxfp1 mice showed a 22% decrease in vessel size at the venous outflow tract 14 d after AVF surgery. Furthermore, a 43% increase in elastin content was observed in the lesions of Rxfp1 mice and coincided with a 41% reduction in elastase activity. In addition, Rxfp1 mice displayed a 6-fold increase in CD45 leukocytes, along with a 2-fold increase in monocyte chemoattractant protein 1 (MCP1) levels, when compared with wild-type mice. In vitro, VSMCs from Rxfp1 mice exhibited a synthetic phenotype, as illustrated by augmentation of collagen, fibronectin, TGF-β, and platelet-derived growth factor mRNA. In addition, VSMCs derived from Rxfp1 mice showed a 5-fold increase in cell migration. Finally, RXFP1 and RLN expression levels were increased in human AVFs when compared with unoperated cephalic veins. In conclusion, RXFP1 deficiency hampers elastin degradation and results in induced vascular inflammation after AVF surgery. These processes impair OR in murine AVF, suggesting that the RLN axis could be a potential therapeutic target for promoting AVF maturation.-Bezhaeva, T., de Vries, M. R., Geelhoed, W. J., van der Veer, E. P., Versteeg, S., van Alem, C. M. A., Voorzaat, B. M., Eijkelkamp, N., van der Bogt, K. E., Agoulnik, A. I., van Zonneveld, A.-J., Quax, P. H. A., Rotmans, J. I. Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas.

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