Bone, as one of the main tissues of the body, plays an important role in maintaining skeletal structure an‎d function, an‎d the repair of its lesions, especially in extensive injuries, remains a major challenge in medicine. Extensive bone lesions often disrupt the natural healing process due to incomplete regeneration, inflammation, an‎d the risk of infection. Therefore, the development of novel scaffolds with bioactivity, controlled degradability, an‎d antibacterial properties is essential to facilitate bone regeneration. In this study, nanocomposite hydrogels based on thiolated silk an‎d methacrylated hyaluronic acid, containing bioactive metal–organic frameworks (MOF) loaded with melatonin at different concentrations (0, 2, 5, an‎d 10 wt%) were designed an‎d investigated. First, zinc-based MOF nanoparticles were synthesized by hydrothermal method an‎d loaded with melatonin. Structural an‎d physicochemical characterization showed that modification of MOF with 3,3ʹ-dithiopropanoic acid resulted in reduced particle size, improved thermal stability, an‎d increased melatonin loading capacity. These nanoparticles also showed significant antibacterial activity against Staphylococcus aureus an‎d Escherichia coli an‎d were able to effectively reduce the microbial load of infected wounds in an animal model. After preparing thiolated silk an‎d methacrylated hyaluronic acid, these compounds were combined with loaded MOF to obtain nanocomposite hydrogels. Increasing the MOF concentration led to an increase in gelation time. The sample containing 5 wt% MOF had appropriate porosity, high water absorption, controlled degradability, an‎d a gradual melatonin release profile over 14 days. The addition of MOF also improved the compressive strength of the hydrogels, an‎d the 5% sample showed the highest compressive modulus an‎d structural stability. Antioxidant activity test also indicated the ability of this hydrogel to inhibit free radicals. Bioactivity eva‎luation showed that hydrogels containing MOF increased calcium an‎d phosphorus deposition, indicating the ability to induce mineralization. Cellular studies on osteoblasts confirmed that the nanocomposite hydrogel, especially at a concentration of 5%, had the highest cell viability, adhesion, an‎d differentiation. Overall, the results of this study showed that the thiolated silk/methacrylated hyaluronic acid nanocomposite hydrogel containing 5% MOF loaded with melatonin has high potential as a novel scaffold for application in bone tissue repair due to its suitable mechanical properties, controlled drug release, antioxidant activity, an‎d favorable biocompatibility.

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مريم فنائي كهراني

فاطمه داور , زهرا طالبي مزرعه شاهي