{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:49:53Z","timestamp":1782308993690,"version":"3.54.5"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Diabetic foot infections (DFIs) are characterized by persistent bacterial biofilms and impaired host immune defenses. Within the diabetic microenvironment, peripheral neuropathy disrupts neuro-immune feedback loops, contributing to the arrest of resident macrophages in a pro-inflammatory M1 phenotype. This phenotypic arrest impairs efferocytosis and sustains chronic inflammation, which conventional antimicrobial therapies frequently fail to resolve. Electroacupuncture (EA) serves as a neuromodulatory intervention capable of reversing this immune dysfunction. By stimulating specific somato-autonomic reflexes\u2014including the vagal-adrenal and sympathoadrenal axes\u2014EA activates the systemic cholinergic anti-inflammatory pathway (CAP). The subsequent release of neurotransmitters, acting on receptors such as the \u03b17 nicotinic acetylcholine receptor (\u03b17nAChR) on macrophages, inhibits pro-inflammatory cascades and promotes polarization toward the pro-repair M2 phenotype. Concurrently, EA-induced localized neuropeptide release and vasodilation mitigate the ischemic microenvironment, providing metabolic support for sustained pathogen clearance. Furthermore, this review proposes a translational \u201cVanguard and Commander\u201d approach, integrating the localized biofilm-disrupting properties of advanced antimicrobial biomaterials (the \u201cvanguard\u201d) with the sustained immune reprogramming mediated by EA (the \u201ccommander\u201d). This integration links material science with bioelectronic neuromodulation to coordinate the tissue repair process spatiotemporally. Ultimately, this combined approach provides an opioid-sparing, integrative therapeutic strategy for the management of refractory diabetic wound infections.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1874221","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T09:16:23Z","timestamp":1782292583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative neuromodulation in diabetic foot infections: electroacupuncture-driven macrophage reprogramming and synergy with antimicrobial biomaterials"],"prefix":"10.3389","volume":"16","author":[{"given":"Yi","family":"Lu","sequence":"first","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Graduate School, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Gong","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Graduate School, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoyong","family":"Fu","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Graduate School, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Xie","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Graduate School, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Graduate School, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyi","family":"Ma","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Graduate School, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyao","family":"Wu","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilan","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanfu","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26164917","article-title":"Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds","volume":"26","author":"Aitcheson","year":"2021","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104622","article-title":"The cholinergic anti-inflammatory pathway in humans: state-of-the-art review and future directions","volume":"136","author":"Alen","year":"2022","journal-title":"Neurosci. 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