Innovative approaches to managing diabetic wounds with smart bioactive dressings

A recent study published in Engineering delves into the advancements in wound management, specifically focusing on microenvironment-sensitive bioactive dressings for diabetic wounds. Diabetic wounds (DWs) are a major complication of diabetes mellitus. With the global diabetic population on the rise, the number of people at risk of developing DWs is also increasing. The lifetime risk of developing DWs for diabetics ranges from 19% to 34%, and the recurrence rate is high, posing a significant challenge to patient health.

The healing process of DWs is complex and differs from that of acute wounds. In the hemostasis phase, patients with diabetes often experience abnormal platelet aggregation and fibrin network formation. The inflammatory phase is prolonged due to impaired immune cell function, imbalance of inflammatory mediators, enhanced oxidative stress, microvascular complications, and an increased risk of secondary infections. During the proliferation phase, the normal function of cells like keratinocytes and fibroblasts is impaired, and in the remodeling phase, the quality of collagen deposition is poor, making the wound vulnerable to recurrence.

The microenvironment of DWs is characterized by high glucose levels, persistent inflammation, persistent infection, hypoxia, disordered factors, and dynamic pH disruption. High glucose promotes the accumulation of advanced glycation end-products (AGEs), which not only extend the inflammatory response but also affect the migration and proliferation of key healing cells. Persistent inflammation is caused by factors such as excessive reactive oxygen species (ROS) production and imbalanced macrophage polarization. Persistent infection, often due to the formation of biofilms, is difficult to treat. Hypoxia impairs the functionality of cellular populations and angiogenesis. Disordered factors, including the over-accumulation of AGEs, ROS, and matrix metalloproteinases (MMPs), disrupt the normal wound-healing process. The pH of DWs is often alkaline, which promotes bacterial growth.

To address these challenges, researchers have developed microenvironment-sensitive bioactive dressings with on-demand regulation. These dressings can be classified into passive and active on-demand management strategies. Passive on-demand management includes glucose-sensitive management (using materials like concanavalin A (Con A), glucose oxidase (GOx), and phenylboronic acid (PBA) derivatives), pH-sensitive management (adjusting drug release based on pH changes), antioxidant, anti-inflammation, and anti-infection management (scavenging ROS, inhibiting bacteria, and reducing inflammation), factors-sensitive management (targeting AGEs and MMPs), and temperature- and moisture-sensitive management (responding to temperature and moisture changes). Active on-demand management strategies involve ultrasound-sensitive management (triggering drug release with ultrasound), magnetic-sensitive management (using magnetic fields for therapy), and light-sensitive management (utilizing photocatalytic and photothermal technologies).

However, the clinical application of bioactive dressings still faces challenges. The biosafety of innovative materials needs to be rigorously analyzed, and they must comply with regulatory standards. Different dressings may require different Food and Drug Administration approval pathways, depending on their characteristics. Future research should focus on smart response mechanisms, delivery system construction, biocompatibility, mechanical property optimization, integration of sensors, and multifunctional design to further improve the efficacy of these dressings in treating diabetic wounds.