**3.2.3 Surface modification through electrostatic interactions**

16 Biomedicine

Overall, surface modification achieved via hydrophobic interaction and insertion of hydrophobic chains into the cell membrane demonstrated a limited retention time. For PEGlipids this time depends on the alkyl chain length of lipid chains (Inui et al., 2010). The longer alkyl chains allowed PEG-lipid molecules to retain longer on the cell membrane. However, the overall retention time was no longer than 48 hours before the all molecules disappeared from the islets surfaces. Incorporation of hydrophobic molecules into the cell membrane leads to their uptake into the cell cytoplasm. Adding amphiphilic part to the structures prevents the uptake but molecules are released into the surrounding media.

Fig. 4. Top: (a) Chemical structure of oligo(dT)20-conjugated PEG-lipid (oligo(dT)20-PEGlipid). (b) Urokinase is modified with Sulfo-EMCS to introduce maleimide groups, and then

(c) Oligo(dT)20-PEG-lipid is incorporated into the cell surface by the hydrophobic interaction between alkyl chains and the lipid bilayer of the cell membrane. Oligo(dA)20-urokinase is applied to cells carrying oligo(dT)20. Urokinase is conjugated on the cell surface through oligo(dT)20 -oligo(dA)20 hybridization. Bottom: Confocal laser scanning microscopic images of urokinase--modified-islets which were subjected to immunostaining for urokinase. Islets were modified with oligo(dT)20-PEG-lipids and then oligo(dA)20-urokinase. The urokinasemodified-islets just after treatment, after 1 and 2 days of culture. Reprinted with permission

oligo(dA)20-SH is conjugated on urokinase through the thiol/maleimide reaction.

from Takemoto et al., 2011. Copyright 2011 American Chemical Society.

Heparin has an affinity to a number of plasma proteins and growth factors including endothelium and vascular endothelium growth factors. Employing this property of heparin, the synthetic heparin-binding peptide amphiphile was used to immobilize heparin and, subsequently, growth factors on islet surfaces (Chow et al., 2010). Initial immobilization of the amphiphile on the islet surfaces can be achieved *via* electrostatic interactions of positively charged amphiphile and negatively charge cell membrane (Fig. 3, A4). Later, negatively charged heparin can be bound to the amphiphile. The so-formed amphiphileheparin complex coating on the islets surface was able to bind and retain growth factors up to 48 hours. The complex nanostructures provide extracellular matrix-like scaffold for the encapsulated islets for supporting their viability. Such immobilization of growth factors does not affect viability or function, yet, they are able to stimulate an angiogenic response in the islets.
