2. Academic Validation
  3. Surficial nano-deposition locoregionally yielding bactericidal super CAR-macrophages expedites periprosthetic osseointegration

Surficial nano-deposition locoregionally yielding bactericidal super CAR-macrophages expedites periprosthetic osseointegration

  • Sci Adv. 2023 Jun 2;9(22):eadg3365. doi: 10.1126/sciadv.adg3365.
Ziyang Li 1 2 3,  Shengchang Zhang 1,  Zhipeng Fu 1,  Ying Liu 1,  Zhentao Man 2 3,  Chongdeng Shi 1,  Chunwei Tang 1,  Chen Chen 1,  Qihao Chai 2,  Zhenmei Yang 1,  Jing Zhang 1,  Xiaotian Zhao 1,  Hailun Xu 3,  Maosen Han 1,  Yan Wang 1,  Ziyang Liao 1,  Gongchang Yu 4,  Bin Shi 4,  Kun Zhao 1,  Wei Li 2 3,  Xinyi Jiang 1
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Technology Research and Evaluation of Drug Products and Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, Shandong Province 250012, China.
  • 2 Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province 250021, China.
  • 3 Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, China.
  • 4 Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
PMID: 37256944 DOI: 10.1126/sciadv.adg3365
Abstract

Tracking and eradicating Staphylococcus aureus in the periprosthetic microenvironment are critical for preventing periprosthetic joint Infection (PJI), yet effective strategies remain elusive. Here, we report an implant nanoparticle coating that locoregionally yields bactericidal super chimeric antigen receptor macrophages (CAR-MΦs) to prevent PJI. We demonstrate that the plasmid-laden nanoparticle from the coating can introduce S. aureus-targeted CAR genes and caspase-11 short hairpin RNA (CASP11 shRNA) into macrophage nuclei to generate super CAR-MΦs in mouse models. CASP11 shRNA allowed mitochondria to be recruited around phagosomes containing phagocytosed bacteria to deliver mitochondria-generated bactericidal Reactive Oxygen Species. These super CAR-MΦs targeted and eradicated S. aureus and conferred robust bactericidal immunologic activity at the bone-implant interface. Furthermore, the coating biodegradability precisely matched the bone regeneration process, achieving satisfactory osteogenesis. Overall, our work establishes a locoregional treatment strategy for priming macrophage-specific bactericidal immunity with broad application in patients suffering from multidrug-resistant Bacterial infection.

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