Page 194 - Biodegradable Polyesters

172 7 Electrospun Scaffolds of Biodegradable Polyesters: Manufacturing and Biomedical Application

forming an amine-reactive O-acylisourea intermediate. This molecule is unstable
in aqueous solution and if it does not react with an amine, it is hydrolyzed and
regenerated into the carboxyl group. The use of NHS stabilizes the O-acylisourea
ester intermediate by creating a semi-stable amine-reactive NHS ester [141].
Commonly, the covalent functionalization consists of three steps: (i) pretreatment
of polyester scaffold for increase of its hydrophilicity by hydrolysis, for example;
(ii) activation of the polyester chain with EDC/NHS intermediates, and (iii)
binding the polyester with biomolecules [12, 142]. The covalent binding prevents
the easy leach out of the biomolecule from the surface of polyester fibers when
incubated over an extended period [14]. However, it is very important that the
functionality of the biomolecule is evaluated after its immobilization on the
surface of the scaffold. During the reaction, the biomolecule can have its active
sites chemically modified and become inactive [12].
In addition to improving the adhesion and development of cells, the function-
alization of electrospun polyesters can introduce to them specific biological func-
tionalities. An example is the functionalization of PCL with heparin anticoagulant
for vascular tissue engineering application. A major cause of vessel graft failures
is the adsorption of blood proteins in the inner biomaterial surface. This process
provokes a sequence of reactions that lead to the formation of thrombus and loss of
the graft. Therefore, with the aim of improving material patency, some studies have
been focused on the functionalization of vascular scaffolds with biomolecules
which present anticoagulant properties. PCL is extensively used for the produc-
tion of vascular scaffolds owing to its adequate mechanical integrity, biodegrad-
ability, and easy processing ability. Studies have shown that the conjugation of
heparin with PCL fibers significantly reduces the adsorption of plasma proteins,
such as albumin and fibrinogen on their surface [49, 143]. The negatively charged
sulfate groups from heparin in the PCL scaffolds create binding sites for various
positively charged growth factors [38, 142]. Heparin-functionalized PCL fibers,
which were subsequently attached to vascular endothelial growth factor (VEGF), a
potent angiogenic protein, were developed. It was shown that heparin–PCL fibers
possess a higher loading capability of VEGF than PCL fibers [143]. The association
of VEGF with PCL–heparin scaffolds also gives them angiogenic properties.

7.3.2
Pretreatments: Association of Polyesters with Biomolecules before Electrospinning

7.3.2.1 Blends of Polyesters with Other Polymers and/or Biomolecules
The biological performance of polyesters can be improved by their association in a
blend form with natural polymers or other specific molecules. The obtained blend
is submitted to the electrospinning process for production of a hybrid scaffold.
Natural polymers are frequently extracted from human or animal ECM and
exhibit inherent bioactivity with sequences which are able to promote cell adhe-
sion. However, these polymers have poor physico chemical properties. Processing
is difficult and they present weak mechanical characteristics and a rapid degra-
dation rate [144]. Meanwhile, as explained above, the polyester polymers provide