Polymer-Dependent Morphology Development of Biodegradable Porous Microspheres with Amphiphilic PEG-PDLLA Incorporation

Biodegradable porous microspheres hold considerable promise as regenerative fillers, injectable biomaterials, tissue-engineering scaffolds, and drug-delivery carriers; however, how polymer properties and amphiphilic modification jointly influence pore formation remains insufficiently understood. In this study, porous microspheres composed of poly(D,L-lactide) (PDLLA), poly(L-lactide) (PLLA), poly(ε-caprolactone) (PCL), and amphiphilic PEG-PDLLA were fabricated by a porogen-assisted solvent evaporation method, with PEG-PDLLA incorporated as an amphiphilic morphology-modifying polymer component. The relationships among polymer type and molecular weight, particle size, porogen incorporation, PEG-PDLLA incorporation, and microsphere morphology were evaluated using scanning electron microscopy, tapped-density porosity analysis, laser diffraction, Brunauer–Emmett–Teller (BET) surface area analysis, micro-computed tomography (Micro-CT), and differential scanning calorimetry (DSC). PDLLA exhibited the highest corrected density-derived porosity index (42.4%), followed by PLLA (30.9%) and PCL (13.6%). Smaller PDLLA microspheres showed higher corrected density-derived porosity, reaching 50.5% at a median particle diameter (D50) of 28.7 μm. PEG-PDLLA incorporation was associated with the formation of surface-open pores and heterogeneous internal architectures as well as increased nitrogen-accessible BET surface area and pore volume, with response exhibited in a polymer-dependent manner. Micro-CT showed differences in internal density distribution and architecture between PLLA and PLLA/PEG-PDLLA microspheres, while DSC revealed polymer-dependent thermal characteristics without fundamentally altering the characteristic thermal transitions of the host polymers. Overall, porous microsphere formation was associated with polymer physicochemical properties, PEG-PDLLA-associated amphiphilic morphology modification, molecular weight, particle size, porogen incorporation, and emulsion/solidification behavior. These findings provide a comparative framework for investigating formulation strategies for biodegradable porous microspheres with tunable architecture and surface accessibility for regenerative medicine and controlled drug-delivery applications.