A Regio‐ and Stereoselective Ring‐Opening Polymerization Approach to Isotactic Alternating Poly(lactic‐co‐glycolic acid) with Stereocomplexation

Poly(lactic‐co‐glycolic acid) (PLGA) has been widely employed for various biomedical applications owing to its biodegradability and biocompatibility. The discovery of the stereocomplex formation between enantiomeric alternating PLGA pairs underscored its potential as high‐performance biodegradable materials with diverse material properties and biodegradability. Herein, we have established a regio‐ and stereoselective ring‐opening polymerization approach for the synthesis of stereocomplexed isoenriched alternating PLGA from racemic methyl‐glycolide (rac‐MG). The high sequence and tacticity control was accomplished by an optimized enantiopure scandium catalyst bearing a spiro‐salen scaffold. Varying polymer stereoregularity Pm from 0.4 to 0.91 led to a transformation of the resulting alternating PLGA from amorphous to semicrystalline materials. Notably, the stereocomplexed alternating PLGA demonstrated enhanced melting transition temperature (Tm up to 191 °C) and crystallization rate. This regio‐ and stereocontrolled polymerization represented a versatile approach for the preparation of high‐performance biodegradable PLGA materials.