<br>双金属过氧化物重塑植入相关骨髓炎的微环境,Advanced Healthcare Materials

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双金属过氧化物重塑植入相关骨髓炎的微环境
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2024-03-02 , DOI: 10.1002/adhm.202303529
Xin Guan ₁ , Siyuan Wu ₁ , Sixue Ouyang ₂ , Shuchen Ren ₁ , Naiqian Cui ₁ , Xiaohu Wu ₃ , Dayong Xiang ₄ , Wenting Chen ₅ , Bin Yu _{1,

4} , Peng Zhao ₆ , Bowei Wang _{1,

4}

Affiliation

种植体相关骨髓炎（IAOM）的特点是骨感染和破坏；目前的抗生素治疗和手术清创疗法常常导致耐药性和骨缺损。为 IAOM 开发一种无抗生素杀菌和成骨增强策略具有挑战性。在此，设计了一种 IAOM 定制的抗菌和骨诱导复合材料，该复合材料由铜 (Cu)-锶 (Sr) 过氧化物纳米颗粒 (CSp NPs) 组成，封装在聚乙二醇二丙烯酸酯 (PEGDA) (CSp@PEGDA) 中。双功能CSp NPs表现出过氧化氢（H ₂ O ₂ ）自给和Fenton催化Cu ²⁺离子的释放，以pH响应方式产生大量羟基自由基（ ^· OH）以杀死细菌，同时释放的Sr ²⁺促进细胞增殖、碱性磷酸酶活性、细胞外基质钙化和骨相关基因表达等体外成骨性。 Cu ²⁺和 Sr ²⁺在 CSp NP 中的整合与涂层 PEGDA 水凝胶一起确保了短期和长期稳定和可持续的离子释放。得益于可注射性和光交联能力，CSp@PEGDA能够彻底填充感染部位并原位凝胶化，以实现细菌消除和骨再生，这一点通过临床模拟IAOM小鼠模型的体内评估得到验证。 CSp@PEGDA的这些良好能力恰好满足了多种治疗需求，为植入相关骨髓炎的治疗开辟了一条有希望的道路。

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Remodeling Microenvironment for Implant-Associated Osteomyelitis by Dual Metal Peroxide

Implant-associated osteomyelitis (IAOM) is characterized by bone infection and destruction; current therapy of antibiotic treatment and surgical debridement often results in drug resistance and bone defect. It is challenging to develop an antibiotic-free bactericidal and osteogenic-enhanced strategy for IAOM. Herein, an IAOM-tailored antibacterial and osteoinductive composite of copper (Cu)–strontium (Sr) peroxide nanoparticles (CSp NPs), encapsulated in polyethylene glycol diacrylate (PEGDA) (CSp@PEGDA), is designed. The dual functional CSp NPs display hydrogen peroxide (H₂O₂) self-supplying and Fenton catalytic Cu²⁺ ions’ release, generating plenty of hydroxyl radical (^•OH) in a pH-responsive manner for bacterial killing, while the released Sr²⁺ promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo-associated genes expression. The integration of Cu²⁺ and Sr²⁺ in CSp NPs together with the coated PEGDA hydrogel ensures the stable and sustainable ion release during short- and long-term periods. Benefitted from the injectablity and photo-crosslink ability, CSp@PEGDA is able to thoroughly fill the infectious site and gelate in situ for bacterial elimination and bone regeneration, which is verified through in vivo evaluation using a clinical-simulating IAOM mouse model. These favorable abilities of CSp@PEGDA precisely meet the multiple therapeutic needs and pave a promising way for implant-associated osteomyelitis treatment.

更新日期：2024-03-02

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