Lactate-Initiated and Solvent-Free Ring-Opening Polymerization of Fused Salt-Templated Deep Eutectic Solvent for Biodegradable Macroporous Polyester Scaffolds

Abstract Low-temperature, organocatalyzed ring-opening polymerization (ROP) of deep eutectic solvent (DES) and noneutectic mixtures composed of l-lactide (LLA) and ε-caprolactone (CL) was carried out under solvent-free conditions using ethyl lactate and butyl lactate as biobased initiators. Unlike previously reported DES-mediated ROP systems, this work integrates lactate-based initiators, selective sequential organocatalysis, and fused salt templating to achieve simultaneous polymerization and scaffold formation under mild conditions. This approach allows the direct formation of biodegradable three-dimensional macroporous polyester scaffolds, in which polymer synthesis and structural organization occur in a single step. The eutectic nature of the LLA–CL system was investigated by density functional theory, 1H NMR spectroscopy, and thermal analysis, providing insight into the intermolecular interactions governing phase behavior. Structural characterization of the resulting polyesters by 1H NMR, X-ray diffraction, and differential scanning calorimetry confirmed successful polymerization and the formation of semicrystalline PLLA/PCL scaffolds. Mechanical testing showed that the compressive properties of the scaffolds can be systematically adjusted through control of molar mass and crystallinity by varying initiator type and concentration. Hydrolytic degradation studies revealed gradual mass loss consistent with scaffold composition, while cytotoxicity assays using MC3T3-E1 preosteoblasts indicated suitable cytocompatibility. Overall, this work establishes a solvent-free, low-temperature strategy for the preparation of macroporous biodegradable polyester materials with controllable physicochemical properties.