# Poly(\(\alpha\)-hydroxy Acids)-Based Cell Microcarriers
## 2 Polylactide and Its Copolymers: Towards Tunable Mechanical Properties and Degradation Rates
Other authors have also studied hydrolytic degradation of PDLLA copolymers with various L/D enantiomeric compositions. [PERSON] et al. [32] worked with two PDLAs with a slightly different d-lactide content (1.4% vs. 3.8%). Although the difference in composition between these two materials was slight, the in vitro degradation study revealed a completely different hydrolysis rate. In this sense, PLLA containing 1.4% of D-lactide suffered \(\sim\)25% molecular weight loss over 90 days submerged in water, whereas PLLA containing 3.8% of D-lactide underwent a \(\sim\)45% of molecular weight loss over the same time period, as determined by nuclear magnetic resonance (NMR). [PERSON] and co-workers [33] analyzed the hydrolysis of three PDLAs with a different content of d-lactide units (0.0%, 0.2% and 1.2%). The obtained \(K\) values of these three materials were 0.00043 day\({}^{-1}\) for PLLA containing 0% of D-lactide, 0.00080 day\({}^{-1}\) for PLLA containing 0.2% of D-lactide and 0.00142 day\({}^{-1}\) for PLLA containing 1.2% of D-lactide. All of these results demonstrate that the incorporation of D-lactide to PLLA (or vice versa) is a valid strategy for reducing the crystallinity of the final product, thus the degradation rate was accelerated and the formation of crystalline residues avoided. Lactide and glycolide copolymers have been also considered as a strategy for increasing the hydrolytic degradation rate of PLAs. Polyglycolide (PGA) is a more hydrophilic polymer [34], and it is less resistant to hydrolytic degradation, probably due to the lack of a pendant voluminous methyl group that could hinder the absorption of water and the corresponding cleavage of ester bonds in PLAs. [PERSON] et al. [31] compared the degradation behavior of PLLA, PDLLA (50:50), poly(L-lactide-\(\alpha\)-glycolide) (80:20) (PLGA) copolymer and poly(D,L-lactide-\(\alpha\)-glycolide) (53:47) (PDLGA) copolymer. As previously stated, PDLLA (\(K\) = 0.0088 day\({}^{-1}\)) displayed a much faster degradation rate than PLLA (\(K\) = 0.0009 day\({}^{-1}\)) because of its completely amorphous character. The PLGA copolymer showed a \(K\) of 0.0127 day\({}^{-1}\), demonstrating that the incorporation of glycolide units and the subsequent reduction in crystallinity greatly increases the degradation rate of PLLA. PLGA suffered microstructural rearrangements during degradation and the material shifted from completely amorphous to semi-crystalline due to the reorganization of the L-lactide chains. Finally, the PDLGA copolymer presented a \(K\) of 0.0506 day\({}^{-1}\) due to the incorporation of glycolide units and the preservation of its amorphous nature during the degradation study. This same effect was also observed in other studies [35; 36]. [PERSON] et al. [35] worked with PDLGA porous tissue-engineering scaffolds with different compositions (85:15 vs. 50:50). Scaffolds of PDLGA 85:15 had half-degradation times (defined as the time required to reach the half of the initial molecular weight) of around 11 weeks, whereas scaffolds of PDLGA 50:50 had half-degradation times of around three weeks. Again, the incorporation of more hydrophilic glycolide units significantly increased both in vitro and in vivo degradation rates. Figure 2: Chemical structure of the monomeric units of L-lactide, D-lactide, Glycolide and \(\varepsilon\)-caprolactone. [PERSON] et al. [36] compared the in vitro degradation of tissue-engineering scaffolds made out of PDLLA, PDLGA 85:15 and PDLGA 75:25. As expected, PDLGA 75:25 displayed the highest degradation rate with a value of \(K\) equal to 0.153 week\({}^{-1}\) (half-degradation time = 2.2 weeks), whereas PDLGA 85:15 and PDLLA showed a value of \(K\) equal to 0.074 (half-degradation time = 4.0 weeks) and 0.023 week\({}^{-1}\), respectively (half-degradation time = 11.1 weeks). In view of these results, it could be expected that increasing the glycolide content in PLGA or PDLGA copolymers would always lead to copolymers with faster degradation rates.