Phototherapy techniques for the management of musculoskeletal disorders: strategies and recent advances.

Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques.

Negative-Pressure Wound Therapy Induces Lymphangiogenesis in Murine Diabetic Wound Healing.

BACKGROUND: Decreased lymphangiogenesis contributes to impaired diabetic wound healing. Although negative-pressure wound therapy (NPWT) has been shown to be effective in the treatment of recalcitrant wounds, its impact on lymphangiogenesis remains to be elucidated. In this study, the authors investigate the mechanisms of lymphangiogenesis following NPWT treatment of diabetic murine wound healing. METHODS: Full-thickness dorsal skin wounds (1 × 1 cm 2 ) were excised on 30 db/db mice. The mice were either treated with occlusive covering (control group, n = 15), or received a 7-day treatment of continuous NPWT at -125 mmHg (NPWT group, n = 15). The wounds were photographed on days 0, 7, 10, 14, 21, and 28. Wound tissue was harvested on days 10, 14, 21, and 28 for quantitative analysis. Functional analysis of lymphatic drainage was performed on days 14 and 28 with Evans blue dye tracing. RESULTS: Lymphatic density and diameter, as visualized through podoplanin probing, was significantly higher in the NPWT group compared to the control group ( P < 0.001). NPWT up-regulated the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) at the protein level ( P = 0.04), and significant differences were noted in lymphatic density as assessed by LYVE-1 staining ( P = 0.001). Leukocyte infiltration was significantly higher in the NPWT group ( P = 0.01). A higher speed of wound closure ( P < 0.0001) and greater wound bed thickness ( P < 0.0001) were noted in the NPWT group compared to the control group. CONCLUSIONS: NPWT increased the lymphatic vessel density and diameter with LYVE-1 up-regulation. NPWT therefore plays a positive role in lymphangiogenesis in diabetic wound healing. CLINICAL RELEVANCE STATEMENT: The authors' study investigates the association of NPWT and lymphatics and underlines the importance of a more in-depth investigation of the role of lymphatic vessels in wound healing.

Modulation of Lymphangiogenesis in Incisional Murine Diabetic Wound Healing Using Negative Pressure Wound Therapy.

Objective: Despite the significant function of lymphatics in wound healing, and frequent clinical use of Negative Pressure Wound Therapy (NPWT), the effect of mechanical force application on lymphangiogenesis remains to be elucidated. We utilize a murine incisional wound healing model to assess the mechanisms of lymphangiogenesis following NPWT. Approach: Dorsal incisional skin wounds were created on diabetic mice (genetically obese leptin receptor-deficient mice [db/db]; n = 30) and covered with an occlusive dressing (Control, n = 15) or NPWT (-125 mmHg, continuous, 24 h for 7 days; NPWT, n = 15). The wounds were macroscopically assessed for 28 days. Tissue was harvested on day 10 for analysis. Qualitative functional analysis of lymphatic drainage was performed on day 28 using Evans Blue staining (n = 2). Results: NPWT increased lymphatic vessel density (40 ± 20 vs. 12 ± 6 podoplanin [PDPN]+ and 25 ± 9 vs. 14 ± 8 lymphatic vessel endothelial receptor 1 [LYVE-1]+) and vessel diameter (28 ± 9 vs. 12 ± 2 µm). Western blotting verified the upregulation of LYVE-1 with NPWT. Leukocyte presence was higher with NPWT (22% ± 3.7% vs. 9.1% ± 4.1% lymphocyte common antigen [CD45]+) and the leukocytes were predominately B cells clustered within vessels (8.8% ± 2.5% vs. 18% ± 3.6% B-lymphocyte antigen CD20 [CD20]+). Macrophage presence was lower in the NPWT group. Lymphatic drainage was increased in the NPWT group, which exhibited greater Evans Blue positivity. Innovation: The lymphangiogenic effects take place independent of macrophage infiltration, appearing to correlate with B cell presence. Conclusion: NPWT promotes lymphangiogenesis in incisional wounds, significantly increasing the lymph vessel density and diameter. This study highlights the potential of NPWT to stimulate lymphatic drainage and wound healing of surgical incisions.

Advances in the therapeutic application and pharmacological properties of kinsenoside against inflammation and oxidative stress-induced disorders.

Extensive research has implicated inflammation and oxidative stress in the development of multiple diseases, such as diabetes, hepatitis, and arthritis. Kinsenoside (KD), a bioactive glycoside component extracted from the medicinal plant Anoectochilus roxburghii, has been shown to exhibit potent anti-inflammatory and anti-oxidative abilities. In this review, we summarize multiple effects of KD, including hepatoprotection, pro-osteogenesis, anti-hyperglycemia, vascular protection, immune regulation, vision protection, and infection inhibition, which are partly responsible for suppressing inflammation signaling and oxidative stress. The protective action of KD against dysfunctional lipid metabolism is also associated with limiting inflammatory signals, due to the crosstalk between inflammation and lipid metabolism. Ferroptosis, a process involved in both inflammation and oxidative damage, is potentially regulated by KD. In addition, we discuss the physicochemical properties and pharmacokinetic profiles of KD. Advances in cultivation and artificial synthesis techniques are promising evidence that the shortage in raw materials required for KD production can be overcome. In addition, novel drug delivery systems can improve the in vivo rapid clearance and poor bioavailability of KD. In this integrated review, we aim to offer novel insights into the molecular mechanisms underlying the therapeutic role of KD and lay solid foundations for the utilization of KD in clinical practice.

Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing.

Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs the function of cells involved in the wound healing process, resulting in chronic non-healing wounds. Given the central role of oxidative stress in the pathology of diabetic ulcers, we performed a comprehensive review on the mechanism of oxidative stress in diabetic wound healing, focusing on the progress of antioxidant therapeutics. We summarize the antioxidant therapies proposed in the past 5 years for use in diabetic wound healing, including Nrf2- and NFκB-pathway-related antioxidant therapy, vitamins, enzymes, hormones, medicinal plants, and biological materials.