Hydrogen sulfide (H₂S) is a physiological gasotransmitter known to possess a regulatory role in several tissues, including bone. The exogenous administration by injection of solutions of H₂S-releasing compounds (e.g., GYY4137) has been previously investigated as a novel therapeutic approach for the treatment of bone diseases. Here, GYY4137 was embedded into fibroin sponges, previously shown to be suitable as scaffolds for bone, thanks to their biocompatibility, scalable porous structure, and biodegradability rate. Fibroin porous scaffolds were produced by solvent casting and the particulate leaching method, and GYY4137 was successively incorporated by using dimethyl sulfoxide (DMSO) as vehicle. The process used to produce GYY4137-loaded scaffolds allowed the incorporation of different controlled amounts of GYY4137 into fibroin matrices. The loading process preserved the properties of the system components in the final products, as assessed by SEM, FT-IR, NMR, and different thermal analyses techniques. Release of H₂S from GYY4137 incorporated into the scaffolds was monitored upon incubation in saline solution at physiological pH: H₂S-release kinetic was found to be dependent on the amount of GYY4137. To ensure biocompatibility, mouse fibroblasts and human primary bone marrow stromal cells were seeded onto scaffolds, and short-term viability assays were performed. Results showed that the GYY4137-loaded scaffold did not induce cytotoxicity in any of the cell type tested. Our findings demonstrate that embedding an H₂S-releasing donor in silk fibroin scaffold is a suitable strategy to achieve a long-lasting release of H₂S that preserves cell viability and allows local delivery at sites of tissue injury.

中文翻译：

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丝素蛋白多孔支架与缓释硫化氢试剂（GYY4137）的结合，用于组织工程

硫化氢（H ₂ S）是一种生理性气体递质，已知在包括骨骼在内的多种组织中具有调节作用。通过注射H ₂溶液进行外源性给药先前已经研究了释放S的化合物（例如，GYY4137）作为用于治疗骨疾病的新的治疗方法。在这里，由于其生物相容性，可扩展的多孔结构和生物降解率，GYY4137被嵌入到丝蛋白海绵中，以前被证明适合用作骨骼的支架。通过溶剂浇铸和微粒浸出法生产丝蛋白多孔支架，并以二甲基亚砜（DMSO）为载体相继掺入GYY4137。用于生产负载GYY4137的支架的过程允许将不同控制量的GYY4137掺入丝蛋白基质中。加载过程保留了最终产品中系统组件的特性，这是通过SEM，FT-IR，NMR和其他热分析技术进行评估的。释放H在生理pH下于盐溶液中孵育后，监测掺入到支架中的GYY4137中的₂ S：发现H ₂ S释放动力学取决于GYY4137的量。为确保生物相容性，将小鼠成纤维细胞和人原代骨髓基质细胞接种到支架上，并进行短期生存力测定。结果显示，加载了GYY4137的支架在任何测试的细胞类型中均未诱导细胞毒性。我们的发现表明，在丝素蛋白支架中嵌入H ₂ S释放供体是实现H ₂ S持久释放的合适策略，该H ₂ S保留了细胞活力并允许在组织损伤部位进行局部递送。