NIR-II Neuromodulation Combined with Metabolite-Mediated Immunoregulation for Accelerated Deeply Located Nerve Repair

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Peripheral nerve regeneration is limited by inflammation, lack of growth factors, and slow axonal growth.
• Current nerve guidance conduits struggle with precise neuromodulation in deep tissues.

Purpose of the Study:

• To develop a near-infrared-II (NIR-II) responsive nerve conduit for spatiotemporally controlled neuromodulation in deep peripheral nerve repair.
• To investigate the therapeutic effects of a gut metabolite, indole-3-propionic acid (IPA), combined with photothermal therapy.

Main Methods:

• Fabrication of a nerve conduit with Au nanorod clusters functionalized with IPA and coated with polydopamine (API) on a PLGA film.
• Utilizing NIR-II light (1064 nm) to generate localized heat, activating TRPV1 channels in Schwann cells and modulating IPA release.
• Assessing the conduit's effects on inflammation, angiogenesis, neurotrophic factor expression, and macrophage polarization in vitro and in vivo.

Main Results:

• API nanoclusters converted NIR-II light into localized heat, activating Schwann cells and promoting neurotrophic factor release.
• IPA and polydopamine effectively scavenged reactive oxygen species, suppressed inflammation, and promoted M2 macrophage polarization.
• The conduit enhanced VEGF-driven angiogenesis, upregulated neurotrophic factors (BDNF, NGF), and improved axonal regrowth and functional recovery.

Conclusions:

• The API-functionalized nerve conduit provides a noninvasive, spatiotemporally precise neuromodulation strategy for deep peripheral nerve regeneration.
• This approach orchestrates anti-inflammatory, angiogenic, and neuroregenerative responses, offering a transformative solution for neural tissue repair.
• The study introduces a bioelectronic paradigm merging photothermal neuromodulation with immune metabolic reprogramming for precision neural reconstruction.