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In the present study the combined effect of low-level laser therapy (LLLT) and \u03b1-lipoic acid (LA) on resting RAW 264.7 macrophages cultured in vitro was evaluated. Cells were cultured on LA-modified poly(\u03b5-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\u00a0nm, 200 mW, 5\u00a0J\/cm\u00b2, 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-\u03b1 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.<\/jats:p>","DOI":"10.1038\/s41598-026-43877-y","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:26:29Z","timestamp":1773847589000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of resting macrophage activity via low-level laser therapy (LLLT) and \u03b1-lipoic acid: an in vitro study using a PCL-based biomaterial"],"prefix":"10.1038","volume":"16","author":[{"given":"Anna","family":"\u015acis\u0142owska-Czarnecka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Matu\u0142a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Stodolak-Zych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Lizak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Homa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Stenka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Chadzinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Bac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"issue":"1","key":"43877_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12915-017-0392-4","volume":"15","author":"S Gordon","year":"2017","unstructured":"Gordon, S. & Pl\u00fcddemann, A. 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