Photothermal-responsive nanocomposite injectable hydrogel capable of programed peroxidase-mimicking catalysis and immunomodulation and revascularization enables efficient drug-resistant bacterial elimination and comprehensive tissue regeneration

Dec 21, 2024Journal of colloid and interface science

Injectable heat-activated hydrogel that mimics enzymes, controls immune response, and supports new blood vessel growth to fight drug-resistant bacteria and heal tissue

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

A multifunctional hydrogel, UMEMOs/PF-MAL, demonstrates effective spatiotemporal therapy for drug-resistant bacterial infections.

UMEMOs/PF-MAL hydrogel exhibits efficient reactive oxygen species-producing activity and immunomodulation capabilities.
The hydrogel's incorporation of ultrathin medium entropy metal oxides enhances its sol-gel properties and photothermal response.
Under low levels of hydrogen peroxide and near-infrared irradiation, the hydrogel generates hydroxyl radicals that can penetrate bacteria and disrupt biofilms.
Release of magnesium and copper from the hydrogel promotes a shift from inflammatory to anti-inflammatory macrophage responses, aiding tissue remodeling.
The mild photothermal effect improves local blood oxygen circulation and alleviates inflammation, potentially speeding up wound healing.

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Intractable infected wound caused by drug-resistant bacteria remains a severe healthcare problem. Reactive oxygen species (ROS)-based nanocatalytic therapy (ROS-NT) is harnessed to combat drug-resistant bacterial infection. However, it can also cause immune imbalance and excessive inflammatory responses, postponing subsequent wound healing process. Herein, a multifunctional ultrathin medium entropy metal oxides (UMEMOs)-based photothermal-responsive injectable hydrogel (UMEMOs/PF-MAL) was constructed, which is capable of efficient ROS-producing catalysis, immunomodulation, and revascularization. UMEMOs/PF-MAL can further provide an effective spatiotemporal therapy with programmed anti-infection and pro-healing effects to overcome drug-resistant bacterial infected wound. The incorporation of UMEMOs in injectable hydrogel not only endows UMEMOs/PF-MAL hydrogel with excellent peroxidase (POD)-mimicking activity and near infrared (NIR)-triggered photothermal conversion property, but also significantly improves its sol-gel properties. Moreover, UMEMOs/PF-MAL hydrogel can provide favorable release of Mgand Cu, allowing a synergistic effect of immunomodulation, anti-inflammatory, and angiogenesis during pro-healing process. Under triggering with a low level of exogenous hydrogen peroxide (HO) and NIR irradiation, the photothermal-enhanced POD-like activity of UMEMOs/PF-MAL hydrogel enables efficient catalytic generation of hydroxyl radical (OH) at wound sites, which can easily permeate bacteria due to the local photothermal effect, killing drug-resistant bacteria and destroying biofilms. Following the cessation of HOadministration, Mgreleased from UMEMOs/PF-MAL hydrogel causes the polarization of pro-inflammatory M1 to anti-inflammatory M2 macrophages, thereby reducing the inflammatory response and promoting tissue remodeling. Meanwhile, Curelease boosts angiogenesis, and mild photothermal effect improves local blood oxygen circulation and alleviates inflammation, further accelerating wound healing. Therefore, this work offers a multifunctional UMEMOs/PF-MAL hydrogel with programmed anti-infection and pro-healing effects, achieving an efficient spatiotemporal therapy and the optimum therapeutic effect for drug-resistant bacteria infected wound. 2+ 2+ 2+ 2+ 2 2 2 2

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Photothermal-responsive nanocomposite injectable hydrogel capable of programed peroxidase-mimicking catalysis and immunomodulation and revascularization enables efficient drug-resistant bacterial elimination and comprehensive tissue regeneration

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