Utilizing the Foreign Body Response to Grow Tissue Engineered Blood Vessels in Vivo

Abstract

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.

Keywords: Animal models; Foreign body response; Graft; Graft patency; In vivo tissue engineering; Tissue engineering; Translational; Vascular access; Vascular graft; Vascular tissue engineering; Vasculature.

Fig. 1

An overview of the in vivo based concept. I) a biomaterial is implanted in the host. II) The host environment acts as a bioreactor, leading to the encapsulation of the biomaterial with a cellularized fibrous tissue capsule. III) The implant device is removed, leaving only the tissue capsule. IV) The tissue capsule is grafted to the vasculature, creating a TEBV. V) Over time remodeling occurs, where the TEBV transdifferentiates to attain characteristics of a native blood vessel

Fig. 2

An overview of the foreign body response. Following implantation a provisional matrix immediately forms around the implant. Following provisional matrix formation acute inflammation is mainly characterized by the presence of neutrophil, and some monocyte infiltration and differentiation. Chronic inflammation is characterized by the infiltration of monocytes that differentiate to macrophages, and neovascularization. Fibroblasts then proliferate and begin to produce ECM components including collagen. A fibrous capsule forms composed out of a (myo-)fibroblasts, ECM components (mainly collagen), and a one- to two-layer of macrophages. Over time scar tissue forms mainly composed of ECM and collagen, with less fibroblasts. The optimal tissue composition for use as TEBV is a thick cellularized fibrous capsule, which is collagen rich with relatively few inflammatory cells

Fig. 3

Adapted from Rothuizen et al. Showing an autologous tissue engineered blood vessel before, and after grafting. Before grafting α-SMA, vimentin positive (myo-)fibroblasts are present, with frequent CD-45 positive leucocytes and no endothelium (lectin negativity). After grafting the cells are α-SMA, desmin positive SMC like cells with no CD-45 positive cells and an endothelial monolayer [14]