Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 145

VEGF, the most widely used, and its receptors are involved in branch-
ing and remodeling of the vasculature and are, therefore, key regulators of
angiogenesis. They are involved in endothelial cells (EC) migration and in
the maturation process of the nascent vessels [191]. Moreover, VEGF and
its receptors function as vascular permeability factors [192]. Additional
angiogenic factors include the fi broblast growth factors (FGF), platelet-
derived growth factors (PDGF), angiopoietins, and the transforming
growth factors (TGF) [193].

6.7.3.3 Coculture Techniques

Coculture of endothelial cells with target tissue cells and fi broblasts
has shown improved induction and stabilization of angiogenesis.
Endothelialized human tissue-engineered skin consisting of capillary net-
work was introduced by coculturing keratinocytes, dermal fi broblasts, and
human umbilical vein endothelial cells (HUVEC) on 3D porous chitosan/
collagen. Capillary tubes were clearly observed in the coculture system
while were absent in the monoculture of each cell type. The vascularized
engineered skin was then implanted in mice, and the mouse blood was
detected in the in vitro generated vasculature after 4 days [194]. In another
model, cocultured neural progenitor cells and brain-derived immortal-
ized microvascular EC on macroporous hydrogel showed signifi cantly
higher blood vessel density after 6 weeks in vivo ; this is in opposition to
the separately cultured cells [195].
Yet, coculturing for promoting angiogenesis was demonstrated to be
an uneasy task, as cocultivation of EC together with fi broblasts, pericytes,
or vascular smooth muscle cells in fi brin gel did not lead to capillary net-
works, while younger or embryonic fi broblasts were able to support such
endothelial organization in other gel systems [196].
Several studies have recently reported the successful creation of tissue-
engineered vascular grafts with good long-term function by seeding dif-
ferent grafts with bone marrow cells and endothelial progenitor cells. In
culture, these cells have been shown to give rise to 3 blood vessel cell com-
ponents, namely endothelial cells, pericytes, and vascular smooth muscle
cells [197-200].

6.7.3.4 Creating Vascular Patterns

Biomimetic approaches aiming for construct vasculogenesis should
not only target the biological and cellular aspects of vasculogenesis but
should also mimic the 3D hierarchal structure of natural capillary net-
works. Fabrication of channels mimicking the vascular networks lead to
the development of constructs with a preformed capillary “pattern.” The
quest to create such microcirculatory network within the scaffolds in vitro