Strategy for a Biomimetic Paradigm in Dental and Craniofacial Tissue Engineering - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 144

6.7.3 Biomimicry to Reach Vascularization; Simulating a

Vascularizing Milieu

It is now clear that the process of vascularization that occurs in nature is a
multifactorial process where every cellular, molecular, architectural, and
mechanical factor has its is own role. Because these tasks are not yet pre-
cisely and quantitatively defi ned, normal physiological healing process
remains the best strategy for adequate vascularization. Recent research
is trying to incorporate all these factors together in order to mimic this
strategy.

6.7.3.1 Scaffold Properties

In their way of mimicking the biological tissues, synthetically derived
polymer scaffolds should not only be biocompatible and biodegradable,
but should also ensure an optimal interaction with endothelial cells to pro-
mote angiogenesis. To develop scaffolds that fulfi ll these properties, it is
of great importance to investigate how different biomaterials modulate
endothelial cell function [185, 186].
In addition to the cellular interaction with biomaterials, the architec-
ture of the scaffold itself seems to play an important role in adequate
vascularization. The 3D structure of a scaffold by itself could change the
angiogenic activity of incorporated cells [187]. In addition, the pore size of
the scaffolds has been shown to be a critical determinant of blood vessel
ingrowth, which is signifi cantly faster in larger pores (160-270 μm) [188].
Pore interconnectivity has also been shown to be equally if not superiorly
important [189]. Apart from the architecture of the scaffold, the degra-
dation products that are formed during the incorporation process of the
implant might infl uence the ingrowth of blood vessels into scaffolds [180].
The desire to improve the interaction between cells and synthetic scaf-
folds has resulted in a development of hybrid scaffolds in which biologi-
cal matrix components such as laminin, fi bronectin fragments or RGD
sequence, were directly incorporated into synthetic scaffolds. These scaf-
folds are likely to improve microvascular network migration and growth
because the cells can now easily recognize the scaffold surfaces as biologi-
cal components and are therefore likely to result in better cell interaction
with the scaffold, cell migration, spreading, and subsequent vessel infi l-
tration into the scaffold; processes otherwise controlled by the ECM [190].

6.7.3.2 Growth Factor Incorporation

As vascularization is a multifactor process driven by numerous growth
factors (GFs) released at a precise time and concentration, a variety of
angiogenic factors have been tested aiming to further promote vascular-
ization of tissue engineering constructs.