# Poly(\(\alpha\)-hydroxy Acids)-Based Cell Microcarriers
## 2 Polylactide and Its Copolymers: Towards Tunable Mechanical Properties and Degradation Rates
However, it has to be considered that glycolide units are also prone to form more hydrolytically stable crystalline domains when their content in the copolymers reaches a specific threshold value. For this reason, PLGA or PDLGA copolymers with a composition of 50:50 or similar, where the crystallization capability of both lactic and glycolide units is restricted, usually display higher degradation rates than the homopolymers (PLA or PGA) and the copolymers with higher content of glycolide [37] that are crystallizable. The (co)polymers presented so far display a very similar mechanical behavior at room and body temperatures, with high elastic modulus and rather low elongation at break values, due to their relatively high glass transition temperatures. These materials are, therefore, clearly inappropriate for numerous tissue-engineering and biomedical applications that require highly flexible biodegradable materials. In these cases, copolymerization of lactide with lower glass transition temperature polymers, such as poly(\(\varepsilon\)-caprolactone) or poly(trimethylene carbonate), could produce a solution to the above-mentioned needs. In this sense, gradual incorporation of \(\varepsilon\)-caprolactone units to PLLA or PDLLA polymers shifts the mechanical properties of the material from glassy plastic to elastomeric. Previous studies [38; 39] have reported a decrease in elastic modulus from ~1700 MPa to ~12 MPa in poly(L-lactide-\(co\)-\(\varepsilon\)-caprolactone) (PLCL) copolymers with \(\varepsilon\)-caprolactone content ranging from 0% to 30%. The incorporation of \(\varepsilon\)-caprolactone also increased the elongation at break of these polymers from ~8% for pure PLLA to ~500% for PLCL with 30% of \(\varepsilon\)-caprolactone. Regarding the hydrolytic degradation behavior of poly(D,L-lactide-\(co\)-\(\varepsilon\)-caprolactone) (PDLCL) and PLCL copolymers, the situation is much more complex than in PDLGA or PLGA copolymers, and contradictory results can be found in the literature [40; 41; 42]. In the case of PDLGA or PLGA copolymers, the addition of glycolide (below the limit where glycolide can also form crystalline domains) accelerates the degradation behavior of PLAs due to the incorporation of hydrolytically less resistant units and a reduction in the crystallinity of PLLA polymers. In PLCL copolymers, the incorporation of \(\varepsilon\)-caprolactone (below the limit where \(\varepsilon\)-caprolactone can also form crystalline domains) to PLAs lowers the crystallization capability of PLLA, but will, at the same time, provide more hydrolytically resistant units. Although these two effects are antagonistic, the results found in literature indicate that the reduction in crystallinity affects the degradation behavior to a larger extent [40; 41; 43]. For example, [PERSON] et al. [40] compared the degradation behavior of three PLCLs having 90:10 (90% L-lactide, 10% \(\varepsilon\)-caprolactone), 75:25 and 50:50 compositions. PLCL 50:50 displayed a completely amorphous character, whereas PLCL 75:25 and PLCL 90:10 had a melting enthalpy (\(\Delta\)H\({}_{\rm m}\)) of 22.3 and 39.1 J\(\cdot\)g\({}^{-1}\), respectively, which correspond to the energy required to melt L-lactide crystals. Samples of PLCL 50:50 lost \(\sim\)25% of its initial mass after six weeks submerged in phosphate buffered saline (PBS), while PLCL 75:25 lost \(\sim\)13% and no mass loss was detected for PLCL 90:10. These results clearly indicate that, despite adding more hydrolytically resistant \(\varepsilon\)-caprolactone units, the reduction in crystallinity played a more important role in the degradation of the studied polymers. A summary of the degradation rates discussed above is shown in Table 2. Considering that various types of samples (i.e., films, plates, three-dimensional scaffolds, etc.) and conditions were employed for these experiments, a direct comparison between different studies cannot be made.