Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China.
Adv Healthc Mater. 2024 Jun;13(16):e2303529. doi: 10.1002/adhm.202303529. Epub 2024 Mar 17.
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 (HO) self-supplying and Fenton catalytic Cu ions' release, generating plenty of hydroxyl radical (OH) in a pH-responsive manner for bacterial killing, while the released Sr promotes the in vitro osteogenicity regarding cell proliferation, alkaline phosphatase activity, extracellular matrix calcification, and osteo-associated genes expression. The integration of Cu and Sr 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.
植入物相关骨髓炎 (IAOM) 的特征为骨感染和破坏；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。开发一种无抗生素的杀菌和促进成骨的策略对治疗 IAOM 具有挑战性。在此，设计了一种针对 IAOM 的抗菌和促骨复合纳米粒子，即铜 (Cu)-锶 (Sr) 过氧化物纳米粒子 (CSp NPs) 被包裹在聚乙二醇二丙烯酸酯 (PEGDA) 中（CSp@PEGDA）。双功能 CSp NPs 显示出过氧化氢 (HO) 自供应和 Fenton 催化 Cu 离子的释放，以 pH 响应的方式产生大量羟基自由基 (OH) 以杀菌，而释放的 Sr 则促进体外成骨作用，包括细胞增殖、碱性磷酸酶活性、细胞外基质钙化和与骨相关的基因表达。CSp NPs 中 Cu 和 Sr 的整合以及涂覆的 PEGDA 水凝胶确保了在短时间和长时间内稳定和持续的离子释放。受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，以消除细菌和促进骨再生，这通过使用临床模拟的 IAOM 小鼠模型进行体内评估得到了验证。CSp@PEGDA 的这些良好能力精确满足了多种治疗需求，为植入物相关骨髓炎的治疗铺平了道路。
