Establishment of a clinically relevant beagle model for periprosthetic joint infection with 3D-printed prostheses and multimodal evaluation
文献类型：期刊论文
| 作者 | Liu, Heng5,6; Fan, Tingting1,6,7; Yuan, Rui1,6,7; Lu, Shuai5,8; Sun, Dadi9; Xun Y(郇勇)2,10; Gong, Maoqi5; Xiao, Honghu5; Wei, Chongbin3; Wang, Hao3 |
| 刊名 | JOURNAL OF ORTHOPAEDIC TRANSLATION
 |
| 出版日期 | 2025-07-01 |
| 卷号 | 53页码:274-285 |
| 关键词 | Periprosthetic joint infection (PJI) 3D printed prosthesis Beagle model Translational biomechanics |
| ISSN号 | 2214-031X |
| DOI | 10.1016/j.jot.2025.05.007 |
| 通讯作者 | Gu, Qi(qgu@ioz.ac.cn) ; Zha, Yejun(zyjtrauma@163.com) ; Jiang, Xieyuan(jxytrauma@163.com) |
| 英文摘要 | Objective: Periprosthetic joint infection (PJI) poses significant challenges to arthroplasty outcomes, necessitating translational animal models for pathogenesis studies and therapeutic development. This study aimed to establish a standardized Beagle PJI model by integrating species-specific 3D-printed femoral prostheses with quantitative bacterial inoculation, while evaluating the dose-dependent effects of Staphylococcus aureus (S. aureus) on infection progression. Methods: Two titanium alloy prostheses were designed using CT-based anatomical data: BFP-C (canine-optimized) and BFP-H (human-derived). Prostheses underwent mechanical compression tests, finite element analysis (FEA) simulating postoperative and osseointegration phases, and in vivo validation in Beagles. The optimized BFP-C was selected for PJI model construction via hemi-hip arthroplasty (HHA), with intraoperative inoculation of S. aureus ranging from 250 to 10<^>8 colony-forming units (CFU). Longitudinal evaluation included radiography (X-ray/CT), mechanical pull-out tests, histopathology (H&E/Masson/Giemsa staining), bacterial cultures, and mobility assessments using open-field behavioural tracking. Results: BFP-C exhibited superior biomechanical compatibility, with 12.3-fold higher yield strength (6836 f 157 N vs. 553 f 49 N) and 97 % reduction in bone strain (0.71 % vs. 20.32 %) compared to BFP-H. All inoculated groups developed PJI with dose-dependent severity: ultra-high-dose (10<^>8 CFU) groups displayed severe osteolysis (pull-out strength: 24 f 8 N vs. 924 f 45 N in controls), biofilm formation, and mobility impairment (74 % reduction in distance travelled, 2003 f 276 cm vs. 7976 f 333 cm in controls), whereas low-dose (250 CFU) groups established PJI with milder manifestations, evidenced by sinus tract formation, 55.1 % reduction in pull-out strength (406 f 15 N vs. 924 f 45 N in controls), and concordant radiological/histopathological signs of infection. Imaging examinations revealed differential osteolytic patterns corresponding to bacterial loads. Combined wound evaluation and microbiological analyses confirmed consistent infection establishment across all replicates. Conclusion: This Beagle PJI model successfully recapitulates clinical infection dynamics, emphasizing the critical role of species-specific prosthesis design and standardized bacterial quantification. The integrated multimodal evaluation system (imaging, biomechanical, and behavioural analyses) demonstrated both the reliability of the model and its sensitivity in detecting infection progression. Its modular design supports customization for studying biofilm-resistant implants or antibiotic delivery systems. These findings not only provide a critical tool for mechanistic PJI research but also establish a theoretical foundation for clinical translation, with the quantitative multimodal framework directly informing diagnostic and therapeutic strategies. Translational potential: Beyond serving as a preclinical platform for anti-infective therapies, the model provides actionable insights into optimizing human prosthetic biomechanics, such as reducing stress shielding through FEA-informed design principles. The 3D printing workflow further demonstrates rapid prototyping capabilities for patient-specific orthopaedic implants. |
| 分类号 | 一类 |
| WOS关键词 | VIRULENCE |
| 资助项目 | National Key R&D Program of China[2024YFC3044700] ; Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes[JYY2023-11] ; Beijing Natural Science Foundation-Changping Innovation Joint Fund Key Research Project[L244014] ; Henan Province 2024 Three 100 Program for Clinician-Scientists[D20240023] ; Capital Medical University Incubating Program[PYZ24146] ; Research Fund Project of Beijing Jishuitan Hospital[JST-HX-2023-001] |
| WOS研究方向 | Orthopedics |
| 语种 | 英语 |
| WOS记录号 | WOS:001527022300002 |
| 资助机构 | National Key R&D Program of China ; Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes ; Beijing Natural Science Foundation-Changping Innovation Joint Fund Key Research Project ; Henan Province 2024 Three 100 Program for Clinician-Scientists ; Capital Medical University Incubating Program ; Research Fund Project of Beijing Jishuitan Hospital |
| 其他责任者 | Gu, Qi，Zha, Yejun，Jiang, Xieyuan |
| 源URL | [http://dspace.imech.ac.cn/handle/311007/102044]  |
| 专题 | 力学研究所_非线性力学国家重点实验室 |
| 作者单位 | 1.Beijing Inst Stem Cell & Regenerat Med, Beijing 100101, Peoples R China; 2.Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China; 3.Beijing AK Med Co Ltd, Beijing 102200, Peoples R China; 4.Beijing Jishuitan Hosp, Guizhou Hosp, Dept Orthoped, Guiyang 550014, Guizhou, Peoples R China 5.Capital Med Univ, Beijing Jishuitan Hosp, Dept Orthoped Trauma, Beijing 100035, Peoples R China; 6.Chinese Acad Sci, Inst Zool, State Key Lab Organ Regenerat & Reconstruct, Beijing 100101, Peoples R China; 7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 8.Beijing Res Inst Traumatol & Orthopaed, Beijing 100035, Peoples R China; 9.Capital Med Univ, Beijing Tongren Hosp, Dept Foot & Ankle Surg, Beijing 100730, Peoples R China; 10.Chinese Acad Sci, State Key Lab Nonlinear Mech LNM, Inst Mech, Beijing 100190, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Liu, Heng,Fan, Tingting,Yuan, Rui,et al. Establishment of a clinically relevant beagle model for periprosthetic joint infection with 3D-printed prostheses and multimodal evaluation[J]. JOURNAL OF ORTHOPAEDIC TRANSLATION,2025,53:274-285. |
| APA | Liu, Heng.,Fan, Tingting.,Yuan, Rui.,Lu, Shuai.,Sun, Dadi.,...&Jiang, Xieyuan.(2025).Establishment of a clinically relevant beagle model for periprosthetic joint infection with 3D-printed prostheses and multimodal evaluation.JOURNAL OF ORTHOPAEDIC TRANSLATION,53,274-285. |
| MLA | Liu, Heng,et al."Establishment of a clinically relevant beagle model for periprosthetic joint infection with 3D-printed prostheses and multimodal evaluation".JOURNAL OF ORTHOPAEDIC TRANSLATION 53(2025):274-285. |
入库方式： OAI收割
来源：力学研究所
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