Background <p>Poly(lactic-co-glycolic acid) (PLGA) is widely employed in tissue engineering and drug-delivery systems due to its biodegradability and biocompatibility. Under physiological conditions, PLGA experiences concurrent hydrolysis, thermolysis, mechanical stress, and fluid sorption, generating acidic byproducts that affect mass loss, mechanical integrity, and drug-release safety. Although hydrolytic and thermal degradation have been studied extensively, the role of mechanical loading in altering degradation kinetics and composition remains unclear.</p> Objective <p>This study investigates how static mechanical loading at physiological temperature influences the surface composition, degradation product evolution, and molecular structure of PLGA 85/15 during hydrolysis.</p> Methods <p>PLGA 85/15 specimens were subjected to static loading at 37&#xa0;°C in aqueous conditions. Fourier-transform infrared spectroscopy (FTIR) was employed to monitor degradation product evolution and changes in surface composition. The results were further correlated with thermal behavior, molecular weight changes, and water uptake behavior.</p> Results <p>FTIR analysis revealed that static loading promoted earlier diffusion and neutralization of carboxylic end groups, delaying carboxylate ion accumulation and slowing the autocatalytic degradation. In comparison, non-loaded samples showed premature carboxylate ion formation, enhanced swelling, and faster autocatalysis. FTIR peak-fitting of methyl and methylene bending regions indicated an increased relative lactide content at the sample surfaces under both loaded and non-loaded conditions.</p> Conclusions <p>Static mechanical loading facilitates the diffusion of acidic byproducts in PLGA, slowing the autocatalytic degradation. In contrast, non-loaded samples retain the degradation products, enhancing the autocatalysis process and degradation rate.</p>