Page 193 - Biodegradable Polyesters

7.3 Improving the Bioactivity of Electrospun Polyesters 171

for bioactivation of electrospun scaffolds can be found in the review by Nune and
colleagues, [138].
A variety of methods have been employed to functionalize polyesters with
bioactive molecules. One approach is to graft the biomolecule in polyester before
it is subject to the electrospinning process. Grafting methods permit control of
the extent of functionalization in all stages. However, using this method after
electrospinning, a part of the bioactive molecules is located in the core of the
fibers, inaccessible for the cells. Therefore, an additional step for polymer purifi-
cation can be necessary. This step can increase the cost of scaffold production.
The polyester modification may also influence its spinnability [139].
Another alternative is the functionalization of polyester after electrospinning.
In this case, bioactive molecules are immobilized either covalently or nonco-
valently onto the polyester scaffold surface. In noncovalent functionalization,
hydrogen bonding, electrostatic, hydrophobic, and van der Waals interac-
tions are responsible for driving the physical adsorption of proteins and other
biomolecules onto the surface of the polyester scaffold [12]. Several factors affect
protein adsorption, such as the composition and characteristics of the surface
of the scaffolds. Some studies have found that proteins attach preferentially
to hydrophilic surfaces. Therefore, before protein adsorption, pretreatment
of the scaffold is commonly employed to increase its surface hydrophilicity.
Hydrolysis, amination, and plasma treatments are frequently employed to
improve the hydrophilicity of polyester scaffolds. These treatments expose or add
hydrophilic groups to the polyester chain, favoring electrostatic interactions with
the biomolecules. Regis and colleagues showed that this type of pretreatment can
affect not only the quantity of protein adsorbed but also its conformation and
accessibility in polyester scaffolds. The group demonstrated that polycaprolactone
(PCL) electrospun scaffolds submitted to an amination pretreatment were able to
recruit and adsorb more fibronectin than scaffolds submitted to alkaline hydroly-
sis. In addition, molecular dynamic (MD) simulations suggested that the scaffold
surface can not only alter the energy of interaction between PCL and fibronectin
but also the orientation and conformation of the adsorbed protein. The RGD
motif in fibronectin molecules appears slightly more exposed on hydrolyzed
PCL scaffolds in comparison with non-treated PCL scaffolds and is much more
exposed on aminated scaffolds. The conformation of the protein and subsequently
of its RGD tripeptide is very important for its activity and it influences specific cell
adhesion [140].
In covalent immobilization of biomolecules onto the fibers, chemical mod-
ifications are made in electrospun polyester in order to produce reactive
functional groups in its chain. Primary amine and carboxylate are chemical
groups frequently used as intermediates of reaction. Through this strategy, the
amino or carboxyl groups present on biomolecules are cross-linked to free
carboxyl or amino groups on activated electrospun polyesters. The 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS)
are the most used intermediary reagents in activation reactions of polyesters.
EDC is a zero-length cross-linking agent which reacts with carboxyl groups