Wearable, Self‐powered, Drug‐Loaded Electronic Microneedles for Accelerated Tissue Repair of Inflammatory Skin Disorders

Abstract

Electrical stimulation (ES) is widely used in physiological and medical sciences, while its application to treat inflammatory skin diseases (ISDs) remains a challenge owing to their natural pathological cuticle barrier and lack of an effective combination with chemotherapy to achieve specific immunomodulation. Here, a wearable, battery-free, multi-component drugloaded electronic microneedle (mD-eMN) system is developed by integrating remodeled metal microneedles loaded with multi-component chemical drugs and flexible triboelectric nanogenerators (TENGs). The system can rapidly release drugs into the site of ISDs and then realize an efficient penetration into cell body and specific immunomodulation under the synergism of pulsed electrons originating from the TENG. Also, the pulsed electrons can promote skin tissue homeostasis reconstruction to alleviate the inflammatory process of ISDs. Sufficient evidence shows that a significant skin inflammation regression of psoriasis (a typical ISDs model) is achieved using the mD-eMN system compared to traditional ES or chemotherapy alone. This innovative wearable mD-eMN system provides an effective flexible electronic and chemical drug joint technological platform for the treatment of ISDs, which is not only suitable for the treatment of psoriasis in this study but also maybe for other ISDs such as diabetic ulcers and skin tumors.

Recent advances of biosensors on microneedles

“…6(a), Feng and colleagues introduced a metal microneedle with a sandwich-like structure coated with multicomponent drugs. 66 These MNs penetrate the skin, facilitating drug delivery to inflammatory sites and thereby enhancing drug efficacy. TENGs generate pulsed electrons that promote drug release and penetration into cells for specific immune modulation.…”

Electrical Stimulation for Immunomodulation

“…It has been reported that continuous as well as pulsed electric fields can influence immune cells such as macrophages by promoting their polarization, cytokine secretion profiles, phagocytic behavior, migration, and differentiation, summarized in Table . In addition to macrophages, electric fields are also known to influence other immune cells such as T and B lymphocytes by modulating their membrane capacities and conductivities which further influence their proliferation, migration, and cytokine profiles. , On the basis of the directionality, two sources of electrical stimulation, namely direct current (DC) and alternating current (AC), have been extensively employed for immunomodulation. , In addition, unidirectional and bidirectional pulsed currents (PCs) which can generate current pulses of around 1 s have been used for immunomodulation owing to lesser electrothermal side effects compared to DC. , …”

“…In contrast to the reported systems, this self-powered device produced pulsed electrons from TENG directly onto the tissues for increasing the penetration of the drugs which initiated immunomodulation by activating the Ca 2+ signaling pathway. The obtained results showed that a TENG output of 1 V resulted in complete release of the drug within 2 h which inhibited the levels of macrophages and T cells and resulted in a high inhibition efficiency closer to that of normal skin, whereas the only ES group and drug group still had 4.8 and 3.8% cells, respectively, hence validating the efficiency of the combined therapy for alleviating skin inflammation . In addition, ES modalities are also used to deliver next-generation drugs such as short interfering RNAs (siRNAs) which are becoming popular due to the increasing problem of drug resistance with conventional drugs.…”

“…In another study, Qian et al in 2023 developed a microneedle based TENG platform for initiating immunomodulation for the treatment of autoimmune disease psoriasis. The electrical field caused an increase in the levels of Arg-1 (M2) and a decrease in iNOS (M1) markers in psoriatic skin, resulting in macrophage polarization by regulating the intracellular calcium signaling . In addition to the mechanical stimulus, temperature stimuli responsive self-powered pyroelectric materials have shown promising results in modulating the macrophage phenotype for antitumor immunity. , Novel immunomodulation strategies based on cold temperature treatment of pyroelectric materials such as Bi 2 Fe 4 O 9 nanosheets (NSs) and black phosphorus in the range 4–37 °C have been used to repolarize the macrophages from the M2 to the M1 phenotype for suppressing tumor metastasis .…”

Material selection and performance optimization strategies for a wearable friction nanogenerator (W-TENG)

“…When used as a thermoplastic, PA rarely appears in the preparation of W-TENGs, 40,41 because the treated PA can form textile fibers, which increase the specific surface area, are suitable for wearing and enhance the output. Qian et al 42 used a PA66 film as a positive friction layer and assembled it with a commercial PTFE film. When applied to the human neck, a voltage of about 0.6 V is generated; when applied to the wrist, a voltage of about 1 V is generated, which indicates the excellent sensitivity of PA66-PTFE-based W-TENGs favorable for detecting small and low-frequency vibrations of the human body.…”