Polylactic acid green gels for fabrication of porous scaffolds

Polylactic acid (PLA) has been approved for various medical devices and continues to attract significant interest in biomedical applications such as drug delivery, implants, and tissue engineering. As a thermoplastic polymer, PLA is typically processed either above its melting temperature or in solution. Herein, we developed a series of green solvent-based PLA organogels (termed PLA green gels), which enabled gel-based PLA processing. We investigated 20 bio-based green solvents for PLA dissolution through solubility parameter-based screening and experimental testing. Four bio-based solvents with low toxicity and high boiling points, namely ethyl lactate (EL), gamma-valerolactone (GVL), dihydrolevoglucosenone (Cyrene™), and dimethyl isosorbide (DMI), were identified as promising candidates for the preparation of PLA green gels. Sol-gel transition, rheological and structural properties of the PLA green gels were thoroughly characterized. Subsequently, porous PLA scaffolds were fabricated from such PLA green gels via injection molding and solvent exchange. Our results have demonstrated the potential of green gel-based PLA manufacturing. More importantly, two distinct solvent-dependent gelation mechanisms were revealed for future PLA biomaterial development: phase separation-induced rapid gelation (in EL and GVL), which resulted in stiff and brittle scaffolds, and crystallization-induced slow gelation (in Cyrene™ and DMI), which produced soft and compliant scaffolds.