Sequential infiltration synthesis (SIS) is a powerful approach for templated growth of solid materials such as oxides or metals that exploits the difference in interaction of a precursor molecule with a polymer or block copolymer. While there have been studies showing that infiltration of trimethyl-alumina (TMA) in polymers can be used to grow Al2O3 there are still many atomic level details of the SIS process that require more investigation, including the origin of the differences in infiltration of TMA into different polymers. In this paper, we investigated in detail the Infiltration of Al2O3 into poly (methyl methacrylate) (PMMA) and poly (lactic acid) (PLA) experimentally and theoretically. SIS was performed in a standard ALD reactor, operating at 70°C in quasi-static mode, using TMA and water as the metal and oxygen precursors, respectively. Operando spectroscopic ellipsometry and ex-situ x-ray photoelectron spectroscopy (XPS) evidenced that Al2O3 incorporation in PLA is significantly higher than in PMMA even if, in both cases, TMA incorporation occurs through the formation of an Al-O covalent bond at the C-O-C group. The extent of swelling of the polymers upon TMA infiltration is assessed and is clearly larger for TMA in PLA than in PMMA. First principles density functional theory (DFT) calculations highlighted that both polymers display swelling upon TMA infiltration, saturating with increasing TMA, consistent with operando ellipsometry observations. The DFT results also show the origin of the larger swelling in PLA compared to TMA. Changes in vibrational modes of carbonyl backbone groups in the polymers are used to demonstrate TMA-polymer …