Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair,Advanced Functional Materials

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Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-01-14 , DOI: 10.1002/adfm.202313122
Renhao Xu _{1,

2} , Yuanyuan You _{2,

3} , Wenyi Zheng _{1,

2} , Li Ma ₃ , Yanzhou Chang ₃ , Shuya Pan ₃ , Yanni He ₂ , Meijun Zhou ₂ , Zhili Xu ₂ , Tianfeng Chen _{2,

3,

4} , Hongmei Liu _{1,

2}

Affiliation

Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound-modulatable hydrogel platform with selenoprotein-mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen-enriched selene-incorporated thin-shell silicon within methacrylate gelatin (O₂-PSSG). The resultant construct orchestrates the modulation of the bone-defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium-containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O₂-PSSG rapidly releases selenocystine ([Sec]₂) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β-catenin pathways and promotes the differentiation of BMSCs. Consequently, O₂-PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US-responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration.

中文翻译：

硒蛋白调节水凝胶用于超声控制微环境重塑以促进骨缺损修复

活性氧（ROS）水平异常和骨缺损内的缺氧微环境是阻碍骨修复过程的重要因素。在此，提出了一种创新的超声可调节水凝胶平台，具有硒蛋白介导的抗氧化作用，可促进骨损伤修复。该水凝胶平台将富氧硒化薄壳硅封装在甲基丙烯酸明胶 (O ₂ -PSSG) 内。由此产生的结构协调骨缺损微环境的调节，从而加速骨再生的过程。超声波（US）用于调节水凝胶的孔径大小，以释放含硒纳米颗粒，促进高效细胞内硒蛋白的原位合成和过氧化氢的消耗。正如预期的那样，O ₂ -PSSG 在 US 控制下快速释放硒代胱氨酸 ([Sec] ₂ )，以清除活性氧并维持骨髓间充质干细胞 (BMSC) 的稳态。随着时间的推移，硒蛋白对系统的作用会增加Wnt/β-catenin通路的激活并促进BMSCs的分化。因此，O ₂ -PSSG 在体外和体内增强 BMSC 的抗氧化能力，缓解缺氧环境，促进成骨分化，并加速大鼠模型的颅骨修复。总之，这项研究表明，设计和构建的美国响应性抗氧化水凝胶是解决骨缺陷和促进骨再生的一种有前途的前瞻性策略。

更新日期：2024-01-14

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