TRPV1 Activation via a Three-Stage Adaptive Heat-Absorbing Hydrogel Drives Neurovascular-Immune Coupling

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Nanotechnology

Background:

• Chronic wound healing is hindered by impaired neurovascular-immune coupling.
• Transient Receptor Potential Vanilloid 1 (TRPV1) channel activation is a therapeutic target, but precise control remains a challenge.

Purpose of the Study:

• To develop a programmable hydrogel system for localized and controlled TRPV1 activation.
• To enhance chronic wound healing by restoring neurovascular-immune coupling.

Main Methods:

• A three-stage adaptive, heat-absorbing hydrogel (HMCG) was engineered using PVA and TSPBA for sprayable application and conformal coverage.
• Calcium-gallic acid metal-organic frameworks (MOFs) were embedded as photothermal converters for efficient heat generation upon near-infrared (NIR) irradiation.
• NIR irradiation triggered sustained release of capsaicin and Ca2+ to activate TRPV1 at a controlled temperature (43°C).

Main Results:

• The HMCG hydrogel demonstrated sol-aerosol-gel adaptivity, ensuring close biointerface contact and controlled thermal regulation.
• NIR irradiation induced localized heating and release of therapeutic agents, activating TRPV1 within the desired window.
• The developed system successfully promoted tissue regeneration in diabetic skin lesion models by restoring neurovascular-immune coupling.

Conclusions:

• The HMCG hydrogel offers a controlled, programmable platform for TRPV1-targeted regenerative therapy.
• This light-heat-chemical coupling approach effectively addresses challenges in chronic wound healing.
• The study establishes a novel strategy for enhancing regenerative medicine applications.