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.

Causal effects and metabolites mediators between immune cell and risk of breast cancer: a Mendelian randomization study.

Introduction: The incidence and mortality of female breast cancer remain high, and the immune microenvironment of breast cancer has undergone significant alterations. However, the impact of blood immune cell levels on the risk of breast cancer is not fully understood. Therefor this study aims to investigate the causal relationship between blood immune cell levels and the risk of breast cancer. Methods: A Mendelian randomization (MR) analysis was employed to assess the causal relationship between immune cells and the risk of breast cancer, as along with their potential mediating factors. Genetic statistics of metabolites breast cancer and immune cells were obtained from the GWAS Catalog, while the genome-wide association study (GWAS) statistics of breast cancer were extracted from the UK biobank. Two-sample MR analysis were performed using inverse-variance weighted (IVW) to ascertain the causal association between immune cells and the risk of breast cancer. Furthermore, 1,400 metabolites were analyzed for their mediating role between immune cells and the risk of breast cancer. Results: MR analysis through IVW method revealed that genetically predicted CD24+ CD27+ B cells were associated with a decreased risk of breast cancer (OR = 0.9978, 95% CI: 0.996-0.999, p = 0.001), while IgD- CD38+ B cells were linked to an increased risk of breast cancer (OR = 1.002, 95% CI: 1.001-1.004, p = 0.005). Additional CD14+ CD16+ monocytes were associated with an increased risk of breast cancer (OR = 1.000, 95% CI: 1.000-1.001, p = 0.005). Mediation analysis revealed a positive causal relationship between IgD- CD38+ B cells and Glycerate levels, with the latter also exhibiting a positive causal relationship with the risk of breast cancer (p < 0.05). Conversely, IgD- CD38+ B cells displayed a negative causal relationship with Succinoyltaurine levels, and the latter also demonstrated a negative causal relationship with the risk of breast cancer (p < 0.05). Conclusion: This MR study provides novel genetic evidence supporting a causal relationship between IgD- CD38+ B cells and the risk of BC. Moreover, it is identified that IgD- CD38+ B cells contribute to an increased risk of BC through both positive and negative mediation effects involving Glycerate and Succinoyltaurine.

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.

Metal-Organic Frameworks and Their Composites for Chronic Wound Healing: From Bench to Bedside.

Chronic wounds are characterized by delayed and dysregulated healing processes. As such, they have emerged as an increasingly significant threat. The associated morbidity and socioeconomic toll are clinically and financially challenging, necessitating novel approaches in the management of chronic wounds. Metal-organic frameworks (MOFs) are an innovative type of porous coordination polymers, with low toxicity and high eco-friendliness. Documented anti-bacterial effects and pro-angiogenic activity predestine these nanomaterials as promising systems for the treatment of chronic wounds. In this context, the therapeutic applicability and efficacy of MOFs remain to be elucidated. It is, therefore, reviewed the structural-functional properties of MOFs and their composite materials and discusses how their multifunctionality and customizability can be leveraged as a clinical therapy for chronic wounds.

NIR-II Fluorescence Imaging Using Indocyanine Green Provides Early Prediction of Skin Avulsion-Injury in a Porcine Model.

Purpose: Currently, skin avulsion-injury reconstruction is mainly based on subjective evaluation of traditional clinical signs. It frequently results in unnecessary tissue loss and incomplete debridement-related infection. This pilot study aimed to develop a novel near-infrared (NIR) II fluorescence imaging method to assess avulsed skin-perfusion status and thus predict its outcome early. Methods: Skin avulsion-injury models were established by avulsing 10×4 cm pedicled flaps on porcine hindlimbs. A clinically available improved NIR-Ι/II multispectral imaging system was applied for NIR imaging using indocyanine green (ICG) fluorescence. Continuous NIR-wavelength filters and dynamic imaging were used to investigate optimal imaging conditions and time window. NIR-Ι/II imaging was synchronously conducted for quality comparison of the two methods. Visual inspection and histological studies were used for assessing the final outcome of avulsed skin. Results: NIR-II fluorescence imaging with a 1,100 nm filter obtained satisfactory performance and reached maximum fluorescence intensity at 1 minute after ICG injection. NIR-II imaging clearly visualized the microvascular network in vascularized avulsed skin and revealed "dark areas" in nonvascularized avulsed skin in a real-time fashion. NIR-II fluorescence imaging demonstrated higher resolution than NIR-I imaging, as indicated by ae higher signal-to-background ratio (2.11) and lower full width at half maximum (6.50614). The dark area of avulsed skin on imaging finally developed to necroses that were confirmed by histology. Conclusion: NIR-II real-time fluorescence imaging clearly maps the microvascular network and shows the perfusion status of avulsed skin at higher resolution than traditional NIR-I imaging, and thus precisely predicts the outcome of avulsed skin early.

Roles of Oxidative Stress and Raftlin in Wound Healing Under Negative-Pressure Wound Therapy.

BACKGROUND: Negative-pressure wound therapy (NPWT) is an effective way to promote wound healing. However, its mechanisms have not been investigated thoroughly. Growing evidence suggests that oxidative stress and Raftlin levels play important roles in wound healing. However, whether NPWT promotes wound healing through this mechanism remains unclear. PURPOSE: Our study focuses on the different levels of oxidative stress and antioxidant response between wounds treated by NPWT and routine dressing change. The objective of this study was to measure the differences in Raftlin levels between the two groups, which is a new biomarker related to wound healing. METHODS: We divided 48 male Sprague-Dawley rats with identical full-thickness skin defects into two groups. At specific times (0, 3, 5, 7, 9, 11, and 13 days after surgery), wound tissue samples were obtained for immunohistochemistry and biochemical analysis. The expression of Raftlin and levels of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured by biochemical analysis. Wound-healing times were also compared. RESULTS: In the NPWT group, MDA levels were significantly decreased on days 3, 5, and 7. Furthermore, the expressions of SOD and CAT were significantly reduced on days 3 and 5. Our data also revealed that Raftlin was significantly upregulated across the whole period of wound healing. Moreover, wound healing in the NPWT group was significantly more rapid (16 days on average) than in the control group (24 days on average). On day 13 post surgery, the wound-healing percentage in the NPWT group was 91%, while that in the control group was 48%. CONCLUSION: NPWT may promote wound healing by upregulating Raftlin and inhibiting oxidative stress levels.