Diabetes mellitus (DM) is a chronic metabolic disorder that currently affects approximately 500 million individuals globally, with the prevalence anticipated to rise significantly in the coming years [1]. Among the various complications associated with DM, impaired wound healing has emerged as a pressing clinical challenge [2]. Persistent hyperglycemia not only delays the healing process but also promotes the formation of bacterial biofilms, which act as protective barriers for pathogens [3]. These biofilms increase pathogen resistance to both host immune responses and conventional therapies. Current treatment strategies for DM wounds typically involve debridement, dressings, infection control, vascular assessment, and glycemic management [4]. However, when used in isolation, these methods often fail to promote rapid wound healing, leading to chronic infections, potential amputations, and even life-threatening consequences [5]. This underscores the urgent need for innovative and effective therapeutic solutions that can not only disrupt biofilm barriers, inhibit bacterial growth, and reduce glucose levels, thereby promoting rapid wound healing.

Microneedles (MNs) represent an innovative minimally invasive transdermal drug delivery technology, providing a highly efficient method for administering therapeutic agents [6]. By disrupting the stratum corneum and penetrating bacterial biofilms, MNs enable the direct delivery of both therapeutic drugs and antimicrobial agents to the site of infection [7], [8]. Among the various types of MNs, hyaluronic acid (HA)-based dissolving MNs have gained significant attention due to their excellent biocompatibility, ease of fabrication, and high drug-loading capacity [9]. In addition, HA possesses intrinsic wound-healing properties, making it particularly suitable for managing chronic wounds associated with impaired healing processes [10]. This combination of therapeutic functionalities enhances the potential of HA-based dissolving MNs as a versatile platform for advanced wound care and antimicrobial therapy.

Effective management of DM wounds requires addressing bacterial infections, which severely hinder the healing process [11]. Chronic hyperglycemia in DM patients fosters bacterial colonization, complicating wound recovery. Therefore, incorporating antimicrobial agents into wound treatments is essential. Among these agents, silver nanoparticles (AgNPs) have garnered significant attention for their strong antimicrobial properties. AgNPs offer excellent stability, controlled release profiles, and high tissue permeability, with a low risk of inducing bacterial resistance [12]. They are widely used in clinical applications like wound dressings and catheters [13]. Integrating AgNPs into MNs offers a promising strategy to enhance antimicrobial effects, making them an ideal solution for DM wound care.

Chronic wounds in DM patients are often characterized by elevated glucose levels, which impair healing and exacerbate infection and inflammation [14]. Research indicates that lowering glucose concentrations at wound sites can improve cellular function, enhance tissue repair, and accelerate healing [15]. Insulin (Ins), a widely used anti-DM drug, not only lowers blood glucose levels but also stimulates cell proliferation and collagen synthesis, promoting tissue regeneration [16]. Incorporating Ins into MNs for transdermal delivery offers several advantages, including rapid glucose reduction at the wound site and precise, minimally invasive drug administration. This approach optimizes Ins’ therapeutic effects, providing an efficient solution for managing chronic wounds.

Building on these research findings, this study proposes the development of dissolving MNs incorporating HA, AgNPs, and Ins to establish a multifunctional therapeutic system for DM wound healing. As a minimally invasive drug delivery platform, these MNs are designed to disrupt bacterial biofilms and enable the targeted delivery of therapeutic agents to wound sites. The HA matrix, serving as the MNs’ structural backbone, offers excellent biocompatibility and biodegradability, supporting inflammation regulation, tissue hydration, and repair. The integration of AgNPs enhances antimicrobial activity by inhibiting bacterial growth and biofilm formation. Concurrently, Ins reduces local glucose concentrations, promotes cell proliferation, and accelerates tissue regeneration. This multifunctional system may provide a novel and effective solution for treating chronic wounds.

To validate this concept, a multifunctional HA-based MN system, termed HAMNs@AgNPs-Ins, was designed and fabricated using a two-step process (as illustrated in Fig. 1A). First, Ins was encapsulated within the HA tip matrix. In the second step, AgNPs were embedded into a mixed solution of polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) to form the MN backing layer. These two components were then assembled to construct the HAMNs@AgNPs-Ins system. Upon insertion into the skin (as shown in Fig. 1B), the HA in the MN tips begins to dissolve, facilitating the gradual release of Ins to regulate blood glucose levels. Simultaneously, this process creates micropores in the skin, allowing AgNPs from the backing layer to penetrate the wound site. Once delivered, the AgNPs release Ag+ ions, which exert potent antimicrobial effects. Both in vitro and in vivo experiments validated the exceptional antimicrobial activity and glucose-lowering efficacy of this novel MN system. Furthermore, preliminary results from a wound healing model in DM rats demonstrated its capacity to enhance wound healing. These findings underscore the promise of HAMNs@AgNPs-Ins as a therapeutic platform for the effective management of DM wounds.