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Impaired fracture healing in type 2 diabetes mellitus (T2DM) poses a significant clinical challenge, primarily due to a compromised bone microenvironment driven by senescent macrophages and their amplifying effects. Reduced hydrogen sulfide (HS) levels are a critical contributor to this pathology. To address this, we developed HydroWrap, an advanced HS-delivery controller designed to modulate distinct stages of macrophage senescence. Under near-infrared (NIR) irradiation, HydroWrap underwent an increase in temperature, causing the hydrogel network to contract and accelerate HS generation. This rapid delivery restores HS levels, alleviating mitochondrial dysfunction and suppressing senescence-associated secretory phenotypes (SASP), thereby interrupting the senescence cascade. In T2DM's hyperglycemic bone microenvironment, HydroWrap provides sustained, glucose-responsive HS release, promoting mitophagy and preventing macrophage senescence progression. This dual mechanism addresses both acute and chronic dysfunctions associated with senescence. studies demonstrated that HydroWrap significantly improved fracture healing by reducing recovery time and enhancing bone quality. These findings underscore the therapeutic potential of modulating macrophage senescence in T2DM using a biocompatible drug delivery system. HydroWrap offers a promising strategy for improving fracture outcomes in diabetic patients and may hold broader applications in senescence-related diseases.
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http://dx.doi.org/10.1016/j.bioactmat.2025.05.007 | DOI Listing |
J Extracell Vesicles
September 2025
Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Osteoarthritis (OA), the prevalent debilitating joint disorder, is accelerated by dysregulated intercellular crosstalk, yet the role of fibroblast-like synoviocyte (FLS)-derived extracellular vesicles and particles (EVPs) in disease progression remains to be elucidated. Here, integrative analysis of clinical specimens, animal models, and publicly available datasets revealed significant alterations in exosomal pathways within OA synovium. Proteomic profiling revealed distinct molecular signatures in EVPs derived from inflammatory and senescent FLSs, reflecting the pathophysiological status of their parent cells.
View Article and Find Full Text PDFJ Orthop Translat
November 2025
Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province, Hainan Provincial Stem Cell Research Institute, School of Basic Medicine and Life Sciences, Hainan Medical University,
Unlabelled: Osteoarthritis (OA) is characterized by the inability of stable and complex joint structures to function as they did, accompanied by inflammation, tissue changes, chronic pain, and neuropathic inflammation. In the past, the primary focus on the causes of joint dysfunction has been on mechanical stress leading to cartilage wear. Further researches emphasize the aging of cartilage and subchondral bone triggered cartilage lesion and osteophyte formation.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
August 2025
Division of Biochemistry and Molecular Biology, Siberian State Medical University, Ministry of Health of the Russian Federation, 634050 Tomsk, Russia.
Background: Sarcopenia is a complex, multifactorial condition characterized by progressive loss of muscle mass, strength, and function. Despite growing awareness, the early diagnosis and pathophysiological characterization of this condition remain challenging due to the lack of integrative biomarkers.
Objective: This study aimed to conduct a comprehensive multilevel profiling of clinical parameters, immune cell phenotypes, extracellular vesicle (EV) signatures, and biochemical markers to elucidate biological gradients associated with different stages of sarcopenia.
J Nutr Biochem
September 2025
Department of Woman-Mother-Child, Division of Pediatrics, DOHaD Laboratory, University of Lausanne and Lausanne University Hospital, 1011 Lausanne, Switzerland. Electronic address:
Background: Individuals born after intrauterine growth restriction (IUGR) have a higher risk of developing metabolic syndrome (MetS) in adulthood. In a rat model, male IUGR offspring exhibit MetS features-including elevated systolic blood pressure, glucose intolerance, non-alcoholic fatty liver disease, and increased visceral adipose tissue (VAT)-by 6 months of age. Female offspring, however, do not.
View Article and Find Full Text PDFRedox Biol
September 2025
Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong First People's Hospital, Medical School of Nantong University, Nantong, Jiangsu, 226000, China; Research Institute for Spine and Spinal Cord Disease of Nantong University, Nantong, Jiangsu, 226000, China. Elec
Spinal cord injury (SCI) is a devastating condition characterized by the accumulation of myelin debris (MD), persistent neuroinflammation, and impaired neural regeneration. Although macrophages are pivotal for MD clearance, the impact of excessive MD phagocytosis on macrophage phenotype and function remains poorly understood. Building upon our prior evidence that exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, mitigates microglia-driven neuroinflammation post-SCI, this study elucidates the therapeutic efficacy and underlying mechanisms of Ex-4 in alleviating macrophage senescence, restoring efferocytotic capacity, and facilitating neural repair.
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