Yizuo Shi

Abstract Diabetic foot ulcers (DFUs), a serious and increasingly common chronic issue among diabetics, often do not respond well to generalized treatment strategies. Hypoxia and the overexpression of reactive oxygen species (ROS), resulting in inflammatory dysregulation and subsequent imbalance in macrophage phenotypes, are critical factors contributing to the prolonged non‐healing of DFU wounds. These two issues often interact in a continuous, problematic cycle. Presently, there is a lack of comprehensive strategies aimed at addressing both of these factors simultaneously to interrupt this detrimental cycle. Herein, an immunomodulatory hydrogel (PHG2) is developed for reshaping the hostile DFU microenvironment. The engineered PHG2 not only removes excess internally‐produced ROS but also generates O 2 , with its efficiency further boosted by local hyperthermia (42.5 °C) activated by near‐infrared light. Through both in vitro and in vivo studies, along with transcriptomic assessment, it is confirmed that PHG2 disrupts the detrimental feedback loop between ROS and inflammation while also lowering the M1/M2 macrophage ratio. Such discoveries contribute to a significant enhancement in the healing process of injuries that undergo a gradual increase in movement, covering wounds from the back, mouth, to the foot. Ultimately, this method provides an easy, safe, and highly effective solution for treating DFUs.

Periodontal disease is a multifactorial, bacterially induced inflammatory disorder characterized by progressive destruction of periodontal tissues. Additionally, diabetes mellitus exacerbates periodontitis, resulting in expedited resorption of periodontal bone. However, methods such as mechanical debridement, anti-inflammatory medications, and surgical approaches often fail to eradicate local infections and inflammation, complicating the reconstruction of periodontal tissue structures. Consequently, there is an urgent need to devise a novel strategy for managing diabetic periodontal conditions. Here, a multifunctional controlled-release drug delivery system (GOE1) is developed by encapsulating self-assembled nanoparticles (consisting of chlorhexidine acetate and epigallocatechin-3-gallate) into a hydrogel matrix composed of gelatin methacryloyl and oxidized hyaluronic acid. In vitro experiments demonstrate that the GOE1 hydrogel possesses good antimicrobial, antioxidant and anti-inflammatory properties, and transgenic sequence genomics further illustrates that IL-17-producing RAW 264.7 macrophages are critical for mediating M1/M2 macrophage transition and provide favorable immune microenvironment. In addition, in vivo experiments reveal that GOE1 significantly ameliorates periodontal tissue inflammation and reduces the loss of alveolar bone by reducing inflammatory infiltration and collagen destruction. Overall, the GOE1 hydrogel offers a promising therapeutic option for managing diabetic periodontitis.

Contemporary options for multidrug-resistant bacteria infected diabetic foot ulcers (IDFUs) are predominantly nonspecific. These IDFU injuries often display prolonged inflammation and delayed tissue repair, mainly attributed to an overabundance of M1 macrophages in the hostile diabetic microenvironment. Although immunomodulatory hydrogels show promise for IDFU-focused care, a targeted, safe transition from M1 to M2 macrophages using simplified techniques remains a significant obstacle. Here, we introduce a hybrid hydrogel (GGG) with inherent immunomodulatory capabilities for IDFUs. GGG is composed of interpenetrating polymer networks featuring gallium-induced self-assembling glycyrrhizic acid and a photo-cross-linked gelatin methacryloyl matrix. Importantly, GGG effectively decreases the ratio of M1 to M2 macrophages in conditions infected with drug-resistant bacteria by disrupting iron metabolism and scavenging reactive oxygen species, which contributes to enhanced treatment results for diabetic wounds. To sum up, the immunomodulatory strategy we present provides a straightforward, safe, and highly effective therapeutic avenue for managing IDFUs.

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers.