In Situ Hydrogel with Immobilized Mn-Porphyrin for Reactive Oxygen Species Scavenging, Oxygen Generation, and Risedronate Delivery in Bone Defect Treatment,ACS Applied Materials & Interfaces

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In Situ Hydrogel with Immobilized Mn-Porphyrin for Reactive Oxygen Species Scavenging, Oxygen Generation, and Risedronate Delivery in Bone Defect Treatment
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-07-24 , DOI: 10.1021/acsami.4c08350
Min Ji Kim ₁ , Soo Bin Yoon _{1,

2} , Han Bi Ji ₁ , Cho Rim Kim ₁ , Jae Hoon Han ₁ , Se-Na Kim ₃ , Chang Hee Min ₃ , Cheol Lee ₄ , Lan Sook Chang ₅ , Young Bin Choy _{1,

2,

3,

6,

7,

8}

Affiliation

We propose a hydrogel immobilized with manganese porphyrin (MnP), a biomimetic superoxide dismutase (SOD), and catalase (CAT) to modulate reactive oxygen species (ROS) and hypoxia that impede the repair of large bone defects. Our hydrogel synthesis involved thiolated chitosan and polyethylene glycol-maleimide conjugated with MnPs (MnP-PEG-MAL), which enabled in situ gelation via a click reaction. Through optimization, a hydrogel with mechanical properties and catalytic effects favorable for bone repair was selected. Additionally, the hydrogel was incorporated with risedronate to induce synergistic effects of ROS scavenging, O₂ generation, and sustained drug release. In vitro studies demonstrated enhanced proliferation and differentiation of MG-63 cells and suppressed proliferation and differentiation of RAW 264.7 cells in ROS-rich environments. In vivo evaluation of a calvarial bone defect model revealed that this multifunctional hydrogel facilitated significant bone regeneration. Therefore, the hydrogel proposed in this study is a promising strategy for addressing complex wound environments and promoting effective bone healing.

中文翻译：

固定锰卟啉的原位水凝胶用于骨缺损治疗中的活性氧清除、氧气生成和利塞膦酸盐输送

我们提出了一种固定有锰卟啉（MnP）、仿生超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的水凝胶，以调节阻碍大骨缺损修复的活性氧（ROS）和缺氧。我们的水凝胶合成涉及硫醇化壳聚糖和与 MnP 缀合的聚乙二醇-马来酰亚胺 (MnP-PEG-MAL)，可通过点击反应实现原位凝胶化。通过优化，选择了具有有利于骨修复的机械性能和催化作用的水凝胶。此外，水凝胶与利塞膦酸盐结合以诱导ROS清除、O ₂生成和持续药物释放的协同效应。体外研究表明，在富含 ROS 的环境中，MG-63 细胞的增殖和分化得到增强，RAW 264.7 细胞的增殖和分化受到抑制。颅骨骨缺损模型的体内评估表明，这种多功能水凝胶促进了显着的骨再生。因此，本研究提出的水凝胶是解决复杂伤口环境和促进有效骨愈合的有前途的策略。

更新日期：2024-07-24

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