Preparation of Uniform PEG-PLLA Microspheres via Membrane Emulsification for Soft Tissue Filling Applications

Skin aging could lead to dermal collagen loss and elastic fiber degradation, ultimately manifesting as skin laxity. We aimed to counteract this by using poly-L-lactic acid (PLLA) microsphere (MS)-based fillers to facilitate long-term volume restoration through collagen regeneration. However, conventional MSs exhibit limitations such as broad size distribution and surface irregularities, which are frequently associated with significant adverse reactions. This study employed shirasu porous glass (SPG) membrane emulsification to fabricate uniform and well-shaped polyethylene glycol-block-poly (L-lactic acid) (PEG-PLLA) MSs. A single-factor experiment was employed to optimize the parameters. The optimal preparation conditions for PEG-PLLA MSs were as follows: PEG-PLLA concentration of 40 mg/mL, polyvinyl alcohol (PVA) concentration of 0.5%, and magnetic stirring speed of 200 rpm. Under the optimal conditions, the average particle size of PEG-PLLA MSs was 58.982 μm, and the span value (SPAN) was 1.367. In addition, a cytotoxicity assay was performed, and the results revealed no significant toxicity of the MSs toward L929 mouse fibroblasts at concentrations below 500 μg/mL. Furthermore, PEG-PLLA MSs significantly enhanced the production of key extracellular matrix (ECM) components—type I collagen (Col-I), type III collagen (Col-III), and hyaluronic acid (HA)—while simultaneously alleviating cellular oxidative stress responses. This work offers a reliable and reproducible fabrication strategy for developing biocompatible MS fillers with controllable particle sizes.