INTRODUCTION

Periodontitis is a common yet often underdiagnosed chronic inflammatory disease that affects the supporting structures of the teeth [1–3]. Chronic inflammation in periodontitis results from the immune system’s prolonged response to bacterial biofilms, leading to tissue destruction and eventual tooth loss [4,5]. Early diagnosis and timely intervention are crucial for controlling inflammation and restoring periodontal health. Currently, conventional diagnostic methods rely on clinical visual inspection and dental radiography, while treatment primarily involves periodontal scaling and systemic antibiotics [6,7]. However, these treatments often fail to prevent recurrence due to incomplete plaque removal, unhealthy lifestyles and poor patient compliance with oral hygiene [8]. Moreover, prolonged immune dysregulation can lead to continuous tissue destruction, necessitating long-term oral care and regular examinations [9,10]. Therefore, there is an urgent need for an electronic device capable of providing molecular-level insights and delivering immunotherapeutic interventions to achieve effective periodontitis management.

Traditional therapies for periodontitis based on oral medications or mouthwash often fail to maintain sustained drug concentrations at the infection site, limiting their therapeutic efficacy [11,12]. Consequently, biomaterial-based in situ delivery systems have emerged as a promising strategy for localized periodontal therapy by enabling sustained or on-demand therapeutic release [13–15]. Antibiotics such as metronidazole and minocycline have been incorporated into commercially available hydrogel systems for topical or injectable use in periodontal pockets [16,17]. In particular, since immune responses play a key role in periodontitis pathogenesis, approaches that directly modulate the local immune microenvironment have attracted increasing attention [18]. Immune-modulatory agents such as cytokines and exosomes have been explored for immune modulation [19–21], but their complex preparation, limited stability and cost might hinder widespread applications. In contrast, microRNAs (miRNAs), small RNA molecules that regulate gene expression, represent an emerging class of biomolecular therapeutics [22–24]. MiRNAs can modulate multiple genes involved in immune responses and suppress pro-inflammatory mediators [25–27]. They can also be synthetically produced at scale, but challenges remain in selecting effective immune-regulatory miRNA, and achieving efficient delivery to target cells.

Effective periodontal management also requires dynamic and precise monitoring of disease biomarkers. Real-time sensing and integration of biochemical information into digital health systems are highly desirable for personalized management of chronic periodontal disease. However, due to the mechanical and physicochemical disparities between living tissues and synthetic devices, developing biocompatible and stable bioelectronic interfaces remains challenging. Recent advances in flexible electronics integrated with biochemical sensors have shown promise in wearable health monitoring [28]. Hydrogels, with their high-water contents and microporous structures, provide a physiologically compatible interface between bioelectronic devices and biological tissues [29–31]. Their programmable responsiveness to biochemical stimuli makes them attractive for both sensing and therapeutic applications [32,33]. While many hydrogel-based sensors rely on optical assays such as colorimetric or fluorescence analysis [34–36], radio-frequency techniques provide a wireless and battery-free detection approach [37–39]. By translating biochemical processes into quantifiable wireless signals, radio-frequency resonators enable non-invasive and dynamic monitoring of local biological microenvironments. Meanwhile, closed-loop bioelectronic platforms that integrate sensing with therapeutic actuation have advanced adaptive treatment strategies [40,41], but the direct coupling of molecular-level inflammatory sensing with localized immunotherapeutic delivery remains largely unexplored.

Herein, we report a hydrogel-based wireless inflammation-responsive electronic system (termed WIRES) that directly interfaces with the immune microenvironment to enable both biosensing and immunomodulatory therapy. The system integrates a matrix metalloproteinase (MMP)-cleavable hydrogel with a soft radio-frequency circuit to convert protease activity into wireless electromagnetic signals. The hydrogel matrix also acts as a carrier for inflammation-triggered release of therapeutic miRNAs that reprogram macrophages toward anti-inflammatory phenotypes. This hydrogel-based bioelectronic platform establishes a closed-loop paradigm that couples immune monitoring with bioresponsive therapy, offering a promising strategy for personalized and minimally invasive management of periodontal inflammation.