Research Progress of Hydrogel Microneedles in Wound Management.

Microneedles are a novel drug delivery system that offers advantages such as safety, painlessness, minimally invasive administration, simplicity of use, and controllable drug delivery. As a type of polymer microneedle with a three-dimensional network structure, hydrogel microneedles (HMNs) possess excellent biocompatibility and biodegradability and encapsulate various therapeutic drugs while maintaining drug activity, thus attracting significant attention. Recently, they have been widely employed to promote wound healing and have demonstrated favorable therapeutic effects. Although there are reviews about HMNs, few of them focus on wound management. Herein, we present a comprehensive overview of the design and preparation methods of HMNs, with a particular emphasis on their application status in wound healing, including acute wound healing, infected wound healing, diabetic wound healing, and scarless wound healing. Finally, we examine the advantages and limitations of HMNs in wound management and provide suggestions for future research directions.

Nonswellable Hydrogel Patch with Tissue-Mimetic Mechanical Characteristics Remodeling In Vivo Microenvironment for Effective Adhesion Prevention.

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.

Nanoarchitecture-Integrated Hydrogel Boosts Angiogenesis-Osteogenesis-Neurogenesis Tripling for Infected Bone Fracture Healing.

Infected fracture healing is a complicated process that includes intricate interactions at the cellular and molecular levels. In addition to angiogenesis and osteogenesis, the significance of neurogenesis in fracture healing has also been recognized in recent years. Here, a nanocomposite hydrogel containing pH-responsive zinc-gallium-humic acids (HAs) nanoparticles is developed. Through the timed release of Zn2+, Ga3+, and HAs, the hydrogel exhibits potent antibacterial effects and promotes angiogenesis, osteogenesis, and neurogenesis. The enhanced neurogenesis further promotes angiogenesis and osteogenesis, forming a mutually supportive angiogenesis-osteogenesis-neurogenesis cycle at the fracture site. The hydrogel achieves rapid infected fracture healing and improves tissue regeneration in mice. This study proposes a comprehensive treatment approach that combines antibacterial effects with the regulation of tissue regeneration to improve infected fracture healing.

From hemostasis to proliferation: Accelerating the infected wound healing through a comprehensive repair strategy based on GA/OKGM hydrogel loaded with MXene@TiO2 nanosheets.

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO2-induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds.

A Whole-Course-Repair System Based on Neurogenesis-Angiogenesis Crosstalk and Macrophage Reprogramming Promotes Diabetic Wound Healing.

Diabetic wound (DW) therapy is currently a big challenge in medicine and strategies to enhance neurogenesis and angiogenesis have appeared to be a promising direction. However, the current treatments have failed to coordinate neurogenesis and angiogenesis simultaneously, leading to an increased disability rate caused by DWs. Herein, a whole-course-repair system is introduced by a hydrogel to concurrently achieve a mutually supportive cycle of neurogenesis-angiogenesis under a favorable immune-microenvironment. This hydrogel can first be one-step packaged in a syringe for later in situ local injections to cover wounds long-termly for accelerated wound healing via the synergistic effect of magnesium ions (Mg2+ ) and engineered small extracellular vesicles (sEVs). The self-healing and bio-adhesive properties of the hydrogel make it an ideal physical barrier for DWs. At the inflammation stage, the formulation can recruit bone marrow-derived mesenchymal stem cells to the wound sites and stimulate them toward neurogenic differentiation, while providing a favorable immune microenvironment via macrophage reprogramming. At the proliferation stage of wound repair, robust angiogenesis occurs by the synergistic effect of the newly differentiated neural cells and the released Mg2+ , allowing a regenerative neurogenesis-angiogenesis cycle to take place at the wound site. This whole-course-repair system provides a novel platform for combined DW therapy.