Projects II

Background

Polycaprolactone (PCL) is a synthetic aliphatic polymer. It has excellent biocompatibility in a sense that when it degrades, it produces non-toxic byproducts but has poor biocompatibility in a sense that it has poor cell-material interaction and thus cells will not adhere on its surface. It also has low cost and easy processability, making it useful for a number of biomedical applications such as drug delivery systems and other tissue engineering applications. Electrospun PCL fibers are especially attractive as a scaffold material because they mimic the fibrous structure of the extracellular matrix (ECM) of many tissues.

A scaffold used for tissue engineering can be considered an artificial extracellular matrix since it provides a surface for the cells to grow on.  However, electrospun PCL has a hydrophobic surface due to the lack of functional groups and thus will not promote cell adhesion. Preliminary studies have shown that the water contact angle, which is a measure of hydrophilicity, of unmodified PCL fibers is about 82. This is considered fairly hydrophobic and literature has shown that cell like hydrophilic surfaces, which is water contact angle of 50 or less. It is now generally accepted in biomaterial community that both very hydrophilic and hydrophobic surfaces are not ideal for cell adhesion. Rather, a moderate hydrophilicity enables the polymer to adsorb proteins [9].

Surface modification of PCL is necessary for its use in tissue engineering due to these challenges. Various approaches have been proposed for modifying synthetic hydrophobic biomaterial polymer surfaces. One of the methods is Sodium Hydroxide (NaOH) treatment which causes the base hydrolysis of esters bonds in PCL fibers creating carboxylate ions (Figure 1). This creation of functional group will increase hydrophilicity of the fibers as well as provide means to covalently attach a bioactive compound to improve the cell-material interaction. NaOH treatment also creates nanoroughness which results in increase of surface area which will result in enhanced cell adhesion. Literature has shown that nanotopography is beneficial for enhanced cellular attachment [2].

Capture2

Fig.1 Reaction of the base hydrolysis of esters

 

Another approach is to immobilize Arginine-Glycine-Aspartic Acid (RGD) peptide on biomaterial surface. Immobilization is essential as it will create a strong anchoring of RGD peptide on surface which ultimately leads to enhanced cell adhesion [6].  RGD peptide is a common motif present in the ligands of extracellular matrix proteins like fibronectin. Immobilizing this peptide onto the PCL fibers will result in the binding of cells to the surface via integrins, which are present on the cell surface. Integrins recognize the RGD motif and bind to it, thus attaching the cell to the surface. RGD will be immobilized on the PCL surface using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) chemistry. Other surface modification methods include polyethylene glycol (PEG) treatment, ionized gas (plasma) treatments, chemical treatments as well as various mechanical modification approaches to creating nanotopography [1] but these methods are not feasible for our project and therefore were not considered.

Midterm Progress Report

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