Programming Degradation and Drug Release Through Micropatterning of PLGA Films

Polymeric films enable spatial and temporal control of drug release, improving therapeutic efficacy while reducing systemic side effects. While most studies focus on polymer blends, copolymer design, or chemical modification, this work investigates how geometry alone regulates degradation and drug release in micropatterned films. To this end, we exploit the μMESH platform, a dual-compartmentalized film composed of regularly patterned poly(lactic-co-glycolic acid) (PLGA) microfilaments arranged to form square openings deposited over a poly(vinyl alcohol) (PVA) microlayer. Four μMESH films with square openings of 5, 10, 20, and 50 μm were fabricated, along with a conventional unpatterned, solid PLGA film (FLAT). These films exhibited different surface area-to-volume ratios (S_a/V), ranging from 0.40 μm^-1 (FLAT) to 1.02 μm^-1 (μMESH with 20 μm openings). After extensive microscopy characterizations, PLGA mass loss (erosion) and molecular weight reduction (degradation) were evaluated for each film over several weeks in different media. Erosion and degradation rates strongly correlated with S_a/V (r = 0.99 and r = 0.92, respectively), with higher S_a/V resulting in slower mass loss and molecular weight decay. Electron microscopy analyses confirmed prolonged structural retention in high S_a/V films, with the μMESH exhibiting 20 μm openings preserving its architecture for at least 60 days, whereas lower S_a/V films (FLAT) showed heterogeneous degradation as early as 14 days. These observations were qualitatively confirmed by in vivo studies. From a pharmacological perspective, docetaxel-loaded films exhibited biphasic release profiles dominated by diffusion, with cumulative drug release increasing with S_a/V (r = 0.97). Overall, these findings demonstrate that the degradation, erosion, and drug release kinetics of PLGA films can be precisely tuned through geometry alone, providing a robust strategy for controlling the performance of implantable polymeric films.