# Poly(\(\alpha\)-hydroxy Acids)-Based Cell Microcarriers
## 2 Polylactide and Its Copolymers: Towards Tunable Mechanical Properties and Degradation Rates  
Among the various biodegradable and/or bioresorbable synthetic polymers employed in the fabrication of cell microcarriers, poly(lactide) (PLA) and PLA-based copolyesters have proven to be the most attractive and useful. PLA is a high strength and high modulus thermoplastic, which can be easily processed by conventional thermoplastic techniques like injection moulding, blow moulding, thermoforming and extrusion [22]. Figure 1 illustrates the PLA cycle from its synthesis to its hydrolytic degradation that results in the formation of lactic acid. PLAs obtained by ring-opening polymerization (ROP) are the most commonly studied examples due to the possibility of an accurate control of the chemistry and production of high molecular weight polymers, compared to the other polymerization strategy (polycondensation). Lactide, which is obtained by the polycondensation of lactic acid followed by a depolymerization into the dehydrated cyclic dimer (Step I in Figure 1) (3,6-dimethyl-1,4-dioxane-2,5-dione), can be polymerized by ring-opening into high molar polymers (Step II in Figure 1). Due to the two stereoforms of lactic acid, the corresponding optically active lactic can be found in two different versions: d,d-lactide and l,l-lactide. In addition, lactic can be formed from one d- and one l-lactic acid molecule yielding d,l-lactide (meso-lactide). PLA is degraded by hydrolytic cleavage of the backbone ester bonds, converting long polymer chains into shorter ones (Step III in Figure 1) ultimately to low molecular weight water soluble oligomers and monomers (Step IV in Figure 1) [23]. Chain scission results in the formation of carboxylic end-groups that, due to their acidic nature, will enhance the rate of further hydrolysis. The simplest polymer in this category is the homopolymer of one stereoisomer of lactic, poly(l-lactide) (PLLA) or poly(d-lactide) (PDLA), which show a glass transition and melting temperature of about 55 \({}^{\circ}\)C and 175 \({}^{\circ}\)C, respectively [24]. It is well-known that crystalline regions in the polymer structure are highly resistant to hydrolytic degradation in regard to amorphous regions. Thus, the degradation and reabsorption rates of the homopolymers are relatively slow due to their high crystallinity [25; 26; 27]. In order to reduce the crystallinity of PLLA or PDLA, accelerate the degradation rate and avoid the formation of highly-resistant crystalline fragments, the copolymerization of l-lactide with other monomers has been proposed [28]. The chemical structures of the monomeric units that will be analyzed in this section are illustrated in Figure 2.  
Figure 1: Schematic illustration of poly(lactide) PLA cycle. Production of the monomer (I), polymerization (II), degradation into shorter polymer chains (III), and, finally, into lactic acid (IV) is summarized. Apart from the homopolymer of one stereoisomer of lactic presented above, other polymers in this category are the copolymers of lactides of different stereoforms, with the combinations mainly affecting the polymer properties. In this sense, various studies [29; 30] have reported a decrease in crystallinity fraction in poly(D,L-lactide) (PDLLA) copolymers when reducing the optical purity (approaching to the racemic mixture of L- and D-enantiomers). As the hydrolytic degradation occurs faster in amorphous regions than in crystalline regions, the reduction in the crystallinity fraction in these polymers clearly accelerate the degradation rate of PLAs. Many studies described in the literature on polylactides are aimed at the hydrolytic degradation of PDLA 50:50, the copolymer resulting from the synthesis of a racemic mixture (50:50) of L- and D-enantiomers. [PERSON] et al. [31] concluded that the degradation rate of PDLLA 50:50 was almost 10 times faster than that of PLLA, with degradation rates (\(K\)) of 0.0088 and 0.0009 day\({}^{-1}\), respectively.