Magnetic Field‐Directed Deep Thermal Therapy via Double‐Layered Microneedle Patch for Promoting Tissue Regeneration in Infected Diabetic Skin Wounds

Abstract

Although near‐infrared (NIR) light‐based photothermal therapies have shown therapeutic potential for infected wounds, the attenuation of NIR light intensity in tissue has severely limited the usage in deep bacterial infections. Herein, magneto‐thermal responsive bilayer microneedles (Fe‐Se‐HA MNs) consisting of functionalized hyaluronic acid (HA), ferro‐ferric oxide (Fe3O4), and micelle‐protected selenium nanoparticles (SeNPs@LAS) are constructed to overcome this challenge based on a self‐designed disk‐shaped electromagnetic field device (Disk‐ZVS). The electromagnetic field generated by the Disk‐ZVS shows virtually no intensity attenuation in living tissue. Finite element simulations showed that the field intensity and electromagnetic loss are concentrated on the tips of Fe‐Se‐HA MNs. The MNs are able to puncture hard scabs, penetrate into bacterial biofilms, and perform effective magnetic‐thermal conversion for deep hyperthermia sterilization. Following, the Fe‐Se‐HA MNs can be gradually degraded by excessive hyaluronidase in diabetic wound to release SeNPs, which reduce reactive oxygen species (ROS) to regulate wound redox homeostasis. Meanwhile, the SeNPs are beneficial to angiogenesis, which facilitates blood vessel formation and promotes wound repair. Therefore, various functions can be achieved for the Fe‐Se‐HA MNs, such as magneto‐thermal disinfection, deep and non‐invasive tissue penetration, anti‐inflammation, and pro‐angiogenesis, which shows great potential as an adjunctive therapy for infected diabetic wounds.

Research Progress of Hydrogel Microneedles in Wound Management

“…This multifunctional microneedle patch demonstrated excellent therapeutic efficacy in treating full-thickness skin wounds in diabetic rats. Similarly, He et al prepared a double-layer HMN capable of slow release of SeNPs (Figure D) . In this microneedle system, cross-linked MeHA formed the structural framework, encapsulating two types of NPs: lipoic acid sodium (LAS)-protected SeNPs (SeNPs@LAS) in the base layer and Fe 3 O 4 at the tips.…”

“…Therefore, HMNs have emerged as a promising therapeutic approach for diabetic wounds. In recent years, increasing research has focused on utilizing HMNs to deliver critical substances such as oxygen, metal ions, NPs, , growth factors, , exosomes, , and stem cells to enhance the healing of diabetic wounds.…”

“…(D) Schematic diagram of the construction of the HMN encapsulated with SeNPs@LAS and Fe 3 O 4 , and its magneto-thermal therapy for infected diabetic wounds. Reproduced with permission from ref . Copyright 2023 Wiley.…”

“…122 Currently, treatment methods for diabetic wounds encompass negative pressure wound therapy, growth factor therapy, stem cell therapy, and autologous skin grafting, etc. 123 Nevertheless, factors such as cost, pain level, and efficacy limit the widespread adoption of these treatment techniques. Therefore, the scientific community has been dedicated to developing cost-effective, safe, and effective methods for the treatment of diabetic wounds.…”

“…Similarly, He et al prepared a double-layer HMN capable of slow release of SeNPs (Figure 6D). 123 In this microneedle system, crosslinked MeHA formed the structural framework, encapsulating two types of NPs: lipoic acid sodium (LAS)-protected SeNPs (SeNPs@LAS) in the base layer and Fe 3 O 4 at the tips. As the GelMA hydrogel gradually degraded due to excess hyaluronidase in diabetic wounds, the release of SeNPs@LAS occurred, exerting antibacterial, anti-inflammatory, and proangiogenic effects of SeNPs.…”