Controlled Synthesis and Crystallization-Driven Self-Assembly of Poly(ε-caprolactone)-b-polysarcosine Block Copolymers

Poly(ε-caprolactone)-<i>b</i>-polysarcosine (PCL-<i>b</i>-PSar) block copolymers (BCPs) emerge as a promising alternative to conventional poly(<i>ε</i>-caprolactone)-<i>b</i>-poly(ethylene oxide) BCPs for biomedical applications, leveraging superior biocompatibility and biodegradability. In this study, we synthesized two series of PCL-<i>b</i>-PSar BCPs with controlled polymerization degrees (<i>DP</i> of PCL: 45/67; <i>DP</i> of PSar: 28-99) and low polydispersity indexes (<i>Đ</i> ≤ 1.1) and systematically investigated their crystallization-driven self-assembly (CDSA) in alcohol solvents (ethanol, <i>n</i>-butanol, and <i>n</i>-hexanol). It was found that the limited solubility of PSar in alcohols resulted in competition between micellization and crystallization during self-assembly of PCL-<i>b</i>-PSar, and thus coexistence of lamellae and spherical micelles. To overcome this morphological heterogeneity, we developed a modified self-seeding method by employing a two-step crystallization strategy (i.e., <i>T</i>_c1 = 33 °C and <i>T</i>_c2 = 8 °C), achieving conversion of micelles into crystals and yielding uniform self-assembled structures. PCL-<i>b</i>-PSar BCPs with short PSar blocks tended to form well-defined two-dimensional lamellar crystals, while those with long PSar blocks induced formation of hierarchical structures in the PCL₄₅ series and polymer aggregation on crystal surfaces in the PCL₆₇ series. Solvent quality notably influenced the self-assembly pathways of PCL₄₅-<i>b</i>-PSar₂₈. Lamellar crystals were formed in ethanol and <i>n</i>-butanol, but micrometer-scale dendritic aggregates were generated in <i>n</i>-hexanol, primarily due to a significant Hansen solubility parameter mismatch. This study elucidated the CDSA mechanism of PCL-<i>b</i>-PSar in alcohols, enabling precise structural control for biomedical applications.