Modulation of resting macrophage activity via low-level laser therapy (LLLT) and α-lipoic acid: an in vitro study using a PCL-based biomaterial.

Modulation of macrophage function represents a promising strategy for promoting tissue remodelling and repair. In the present study the combined effect of low-level laser therapy (LLLT) and α-lipoic acid (LA) on resting RAW 264.7 macrophages cultured in vitro was evaluated. Cells were cultured on LA-modified poly(ε-caprolactone) (PCL) membranes, designed as a controlled release platform. Physicochemical analysis confirmed that LA incorporation decreased PCL crystallinity while increasing membrane surface porosity, providing a biphasic LA release profile. LLLT (808 nm, 200 mW, 5 J/cm², pulsed mode) did not affect macrophage viability but modulated matrix metalloproteinase (MMP-9 and 2) activity and macrophage oxidative-antioxidant potential. Cell culturing carried out on LA-modified membranes (PCL-LA) increased their viability, reduced AK and NO levels as well as TNF-α secretion. Simultaneous treatment with LLLT and LA (PCL-LA-IR) further increased macrophage viability, decreased level of MCP-1/CCL2 chemokine, and modified the presence of pro-MMP-9 as well as the activity of MMP-2, MMP-9 and MMP-9 dimers. Moreover, LA-treated cells showed an increase in antioxidant capacity without oxidative potential being altered. These results indicate that PCL is a stable and effective carrier of LA, and that the observed combined effect of LLLT and LA influences the activity of resting macrophages, which may promote the creation of a favourable environment for regenerative processes. These results also indicate the potential for combined therapies using immunomodulatory biomaterials that support tissue repair to be further developed.