**Author details**

models using the self-assembly method and formed vascular networks with lumen [115]. HMVECs are an easily accessible source because they can be derived from a skin biopsy or any other tissue. The use of HMVECs could be particularly suitable for therapeutic applica‐

The co-culture of dermal fibroblasts and keratinocytes with HUVEC on a chitosan/collagen sponge showed the establishment of a capillary-like network similar to the microvasculature found in vivo [119]. Prevascularization of tissues prior to implantation has yield impressive improvements in regenerative medicine. In 2005, human endothelialized reconstructed skin models revealed an important reduction in the delay of functional vascularization after implantation in mice. Early signs of vascularization were observed in the endothelialized human skin grafts within 4 days following tissue implantation, as opposed to 14 days in the nonendothelialized reconstructed skin. Mouse blood vessels were only detected after 14 days in both models demonstrating that neovascularization is a latter process. The uniform distribution of ECs across the reconstruct ensures adequate perfusion of the entire graft. The colocalization of human and host mouse ECs inside a human capillary within the graft suggests the formation of chimeric microvessels and confirms inosculation between both microvascu‐ lar networks [114] (later confirmed in Gibot *et al*. [120] generated self-assembled tissue).

The progress of endothelialized tissue–engineered dermal substitutes lead to the introduc‐ tion of a new in vitro model of capillary-like network formation in self-assembled skin substitutes without the use of an exogenous scaffold. In this approach, stromal sheets, formed by culturing dermal fibroblast during 4 weeks, were seeded with ECs. To generate the 3D skin, two endothelialized stromal sheets were stacked and allowed to fuse [121] (**Figure 1B**). Although a capillary network was observed, the fact that ECs were seeded in a single plane orientation, on top of the stromal sheets, resulted in a vascularized skin model with mainly a 2D vascular network ratherthan a 3D network. In orderto provide the reconstructed skin with the optimal 3D capillary network, ECs were co-seeded with fibroblasts (**Figure 1D**). Incorpo‐ ration of ECs in the reconstructed model using the reseeding technique produced a capillarylike network with increased tissue elasticity and mechanical strength [88]. Moreover, because fibroblasts were seeded at high density, ECM was readily generated and allowed the dermal stroma to be rapidly embedded with ECs [88].This vascularized stroma had pericyte-like cells that expressed the neuron-glial 2 (NG2) marker, which characterizes the surrounding of

The self-assembly approach is used to generate several tissues for fundamental and clinical research applications. Over the years, adjustments to the stroma elaboration protocols and especially the ECM generation were proposed to improve the quality of the bioengineered

tion because it is best adapted for organ specific reconstructs.

354 Composition and Function of the Extracellular Matrix in the Human Body

*5.3.1.1. Vascularization of self-assembled tissues*

capillary-like structures.

**6. Conclusions**

Ingrid Saba1 , Weronika Jakubowska1 , Stéphane Chabaud1 and Stéphane Bolduc1,2\*

\*Address all correspondence to: stephane.bolduc@fmed.ulaval.ca

1 Experimental organogenesis research center of Laval University /LOEX, University Hospital (CHU) of Quebec - Laval University, Enfant-Jésus Hospital, Quebec City, QC, Canada

2 Department of Surgery, Faculty of Medicine, Laval University, Quebec City, QC, Canada
