**4.2.2 Chemical modification**

PLA does not carry reactive side-chain functional groups. Consequently, the first step of chemical modification is typically a simple surface hydrolysis (with an alkali) or an aminolysis treatment. The hydrophilic –COOH and –OH or reactive –NH2 groups introduced by cleavage of the ester bonds can be used to bind bioactive molecules such as arginine-glycine-aspartic acid (RGD)-containing peptides, chitosan (CS), arginine and lysine, PEG, collagen, and so on to regulate cell adhesion or protein adsorption.

The synthetic RGD-containing peptides could be immobilized on PLA after treatment by hydrolysis or aminolysis (Stupack et al., 2001). Materials prepared by this method provide suitable recognition sites for cell adhesion receptors and biodegradation rates, making them suitable for various applications in fields such as tissue engineering and implant technology. It has also been determined that RGD-conjugated poly(lactic acid-*co*-lysine)(arginineglycine-aspartic acid) nanoparticles (PLA-PLL-RGD NP) are non-toxic and bind more efficiently to human umbilical vein endothelial cells (HUVECs) as compared to bare PLA-PLL NP in vitro. Targeted imaging results obtained in vivo showed that PLA-PLL-RGD can selectively bind to BACP-37 breast cancer cells. Lieb et al. also demonstrated largely increased cell densities and cell proliferation on surfaces modified with RGD-anchored monoaminated poly(ethylene glycol)-*block*-poly(*D*,*L*-lactic acid) (H2N-PEG-PLA), mediated through RGD–integrin interactions (Lieb et al., 2005).

Chitosan (CS) is a biopolymer displaying good biocompatibility, non-toxicity and biodegradability, produced by the alkaline *N*-deacetylation of chitin. The immobilization of this polymer on PLA has been accomplished by coating the surface with chitosan, modified with the photosensitive hetero-bifunctional cross-linking reagent 4-azidobenzoic acid, and irradiation with ultraviolet light to photolyze the azide groups and covalently link the two polymers (Zhu et al., 2002). The -OH and -NH2 groups of chitosan provide further opportunities to introduce a wide range of functional groups on the surface. Thus CS molecules immobilized on PLA were modified with a heparin (Hp) solution to form a polyelectrolyte complex on the surface, which inhibited platelet adhesion and activation, and enhanced cell adhesion.

## **4.3 Outlook of PLA surface modification**

The surface attributes of PLA can be tailored to enhance its hydrophilicity and biocompatiblity through various methods. Unfortunately, all these established methods for surface modification are inherently flawed to some extent. For example, a single plasma treatment can merely improve cell adhesion but cannot accelerate cell growth; non-covalent attachment of a functional material onto a PLA surface is not stable and permanent. An excellent method suggested to solve the second issue is the use of 1,6 hexanediamine for surface aminolysis, followed by conjugation with biocompatible macromolecules such as gelatin, chitosan, or collagen (Zhu et al., 2004). Hong et al. have shown that chondrocyte cells could attach, proliferate, and spread on PLA microspheres coated with collagen in the same way as described above, in particular those having high collagen contents (Hong et al., 2005). It appears that the surface modification of PLA would be best achieved with a combination of distinct approaches, to benefit from the advantages of all the methods. Polysaccharide polyelectrolyte multilayers, including chitosan and dextran sulfate-stabilized silver nano-sized colloids developed by Yu et al. (Yu et al., 2007), were successfully deposited on an aminolyzed PLA membrane in a layerby-layer self-assembly manner. This seemingly easy process resulted in significant improvements in hydrophilicity, antibacterial activity, hemocompatibility, and cytocompatibility for the PLA membrane, thanks to the different attributes of –NH3+ (positive charge), chitosan (biocompatibility), and silver nanoparticles (antibacterial activity). The radiation-induced methods are emerging as powerful surface modification techniques, particularly when relying on PLA photoactivation to create reactive groups or moieties useful to graft specific chemical functionalities. The irradiation of PLA with UV (ozone can be generated from molecular oxygen irradiated with UV in this process), for example, is known to increase fiber adhesion to high surface energy components due to the introduction of photo-oxidized polar groups on the surface (Koo & Jang, 2008). Irradiation followed by grafting has also been used extensively to alter PLA surface characteristics, mainly due to the advantages it offers, namely a low operation cost, mild reaction conditions, selectivity to UV light, and the permanent surface chemistry changes induced (Ma et al., 2000).
