Table 5.
Summary of Preclinical In Vivo Models from the Past Decade Used to Establish and Study Implant-Associated Infections
| models to establish and study implant infections | ||||||
|---|---|---|---|---|---|---|
| animal model | implant/location | pathogen | study duration | key evaluation | summary | ref |
| fish – zebrafish | none | S. aureus SH1000-derived | 3 weeks | (1) histology | bone fracture model in zebrafish | 169 |
| 2.5 × 109 CFU | (2) confocal imaging | |||||
| mice – BALB/C | titanium in femur | S. aureus ATCC 29213 | 4 weeks | (1) CFU count | model to study implant infection biofilms | 170 |
| 2 × 103–5 × 106 CFU | (2) collect blood | |||||
| (3) X-rays | ||||||
| (4) SEM biofilm | ||||||
| (5) histology | ||||||
| mice – BALB/C | titanium in femur | S.aureus ATCC 29213 | 4 weeks | (1) CFU count | model for histology scores of implant infection | 171 |
| 1 × 103 CFU | (2) X-rays | |||||
| (3) histology | ||||||
| mice – BALB/C | stainless steel in tibia | S. aureus USA300 | 2 weeks | (1) CFU count | first animal model of S. agalactiae implant infection | 172 |
| 5 × 105 CFU | (2) micro-CT | |||||
| S. agalactiae COH1 | (3) histology | |||||
| 5 × 105 CFU | (4) TRAP quantify | |||||
| mice – diabetic NOD/ShiLtJ CD1 | stainless steel in femur | S. aureus ATCC 25923 | 4 weeks | (1) CFU count | diabetic model of implant infection | 32 |
| 1 × 103 CFU | (2) collect blood | |||||
| (3) micro-CT | ||||||
| (4) SEM biofilm | ||||||
| (5) histology | ||||||
| mice – C57BL/6 and BALB/C | titanium or poly(ether ether ketone) in femur | S. aureus JAR 06.01.31 | 1 week | (1) CFU count | influence of implant material on implant infection | 115 |
| 9 × 105 CFU | (2) histology | |||||
| mice – C57BL/6 | titanium in femur | P. aeruginosa Xen 41 | 3 weeks | (1) CFU count | Gram-negative implant infection model | 163 |
| 1 × 103–1 × 105 CFU | (2) X-rays | |||||
| E. coli Xen 14 | (3) histology | |||||
| 1 × 103–1 × 105 CFU | (4) In vivo BLI | |||||
| (5) PET imaging | ||||||
| (6) Flow cytometry | ||||||
| mice – C57BL/6 | Ti6Al4V in tibia | S. aureus Xen 36 | 2 and 6 weeks | (1) CFU count | clinically relevant load-bearing model of periprosthetic joint infection | 173 |
| 3 × 105 CFU | (2) collect blood | |||||
| (3) X-rays | ||||||
| (3) SEM biofilm | ||||||
| (4) gait analysis | ||||||
| mice – C57BL/6 | titanium in tibia | S. aureus Xen 36 | 12 weeks, disrupt microbiota | (1) CFU count | role of the gut microbiota on periprosthetic joint infection | 33 |
| 1 × 102 CFU | (2) collect blood | |||||
| (3) X-rays | ||||||
| 5 days, postsurgery | (4) gait analysis | |||||
| (5) bacterial sequencing | ||||||
| mice – C57BL/6 | stainless steel in humerus | S. aureus Xen 36 | 6 weeks | (1) CFU count | model of implant infection in humerus | 174 |
| 1 × 103 CFU | (2) X-ray | |||||
| (3) histology | ||||||
| (4) in vivo BLI | ||||||
| mice – C57BL/6 | stainless steel in tibia | S. aureus Xen 40 | 2 weeks | (1) CFU count | quantitative model of implant biofilm | 175 |
| (2) SEM biofilm | ||||||
| (3) in vivo BLI | ||||||
| rats – Sprague–Dawley | Ti6Al4V in tibia | S. aureus ATCC 25923 | 6 weeks | (1) CFU count | model of implant infection in metaphysis | 176 |
| 1 × 103–1 × 106 CFU | (2) collect blood | |||||
| (3) X-rays | ||||||
| (4) histology | ||||||
| rats – Sprague–Dawley | stainless steel in tibia | S. aureus ATCC 49230 | 4 weeks | (1) CFU count | model of implant infection dependent on bacterial inoculation | 177 |
| 1 × 102–1 × 106 CFU | (2) collect blood | |||||
| (3) X-rays | ||||||
| (4) histology | ||||||
| rats – Sprague–Dawley | metal alloy and high density poly ethylene in femur/tibia | S. aureus clinical MN8 and UAMS-1 | 6 weeks | (1) CFU count | model of knee implant infection | 178 |
| 1 × 102–1 × 104 CFU | (2) collect blood | |||||
| (3) X-rays | ||||||
| (4) histology | ||||||
| rats – Sprague–Dawley | titanium in femur | S. aureus ATCC 49230 | 6 weeks | (1) CFU count | model of implant infection, hematogenous osteomyelitis complication | 12 |
| 1 × 104–1 × 109 CFU | (2) micro-CT | |||||
| (3) histology | ||||||
| rats – Sprague–Dawley | titanium and ultrahigh molecular weight polyethylene in tibia/femur | S. aureus Xen 29 | 4 weeks | (1) CFU count | longitudinal infection model with two implant components that enables monitoring of postsurgery recovery | 179 |
| 2 × 107 CFU | (2) X-rays | |||||
| (3) micro-CT | ||||||
| (4) collect blood | ||||||
| (5) histology | ||||||
| (6) gait analysis | ||||||
| rats – Sprague–Dawley | 3D printed Ti6Al4V + PMMA in tibia | S. aureus ORI16_C02N | 4 weeks | (1) CFU count | model of knee implant infection | 128 |
| 2 × 104 CFU | (2) X-rays | |||||
| (3) collect blood | ||||||
| (4) micro-CT | ||||||
| (5) histology | ||||||
| rats – Sprague–Dawley | stainless steel in femur | S. aureus ATCC 29213 | 1 week | (1) collect blood | model of effect of ethylenediaminetetraacetic acid to decrease implant infection | 180 |
| 1 × 107 CFU | (2) histology | |||||
| E. coli ATCC 25922 | ||||||
| 1 × 107 CFU | ||||||
| rats – Sprague–Dawley | none | S. aureus | 2 weeks | (1) CFU count | 68Ga-citrate for PET imaging of implant infections | 36 |
| 3 × 108 CFU | (2) peripheral quantitative computed tomography | |||||
| (3) histology | ||||||
| (4) 68Ga-citrate-chloride PET/CT imaging | ||||||
| rats – Wistar | poly(ether ether ketone) in tibia | S. epidermidis Epi103.1 | 4 weeks | (1) CFU count | longitudinal micro-CT imaging of implant infection with aerobic and anaerobic pathogens | 116 |
| 1 × 106 CFU | (2) time lapse micro-CT | |||||
| P. acnes Type IA, IB | ||||||
| 1 × 106 CFU | ||||||
| rats – Wistar | poly(ether ether ketone) and titanium in tibia | S. aureus JAR 06.01.31 | 4 weeks | (1) CFU count | model of morphological bone changes near infected implant | 117 |
| 3 × 107 CFU | (2) in vivo micro-CT | |||||
| (3) histology | ||||||
| (4) pull-out testing | ||||||
| rabbits – New Zealand White | 3D printed stainless steel + PMMA in tibia | S. aureus ATCC 29213 | 1 week | (1) CFU counts | 3D printed custom implant for animal models, improve recovery | 34 |
| 5 × 106 CFU | (2) collect blood | |||||
| (3) erythrocyte sedimentation rate | ||||||
| rabbits – New Zealand White | 3D printed stainless steel + PMMA in tibia | S. aureus ATCC 29213 | 1 week | (1) gait analysis | 3D printed custom implant for animal models–improve recovery | 134 |
| 5 × 106 CFU | (2) crystal violet biofilm stain on implant | |||||
| rabbits – New Zealand White | stainless steel in femur | S. aureus ATCC 25923 | 3 weeks | (1) X-rays | model of implant infection following open fracture | 181 |
| 1 × 106 CFU | (2) micro-CT | |||||
| (3) SEM biofilm | ||||||
| (4) histology | ||||||
| rabbits – New Zealand White | TiAl6V4 in tibia | S. aureus ATCC 49230 | 6 weeks | (1) CFU count | model of early implant infections in rabbits | 182 |
| 4 × 105 CFU | (2) X-rays | |||||
| (3) histology | ||||||
| rabbits – New Zealand White | stainless steel in tibia | P. acnes 3 × 107 CFU | 4 weeks | (1) CFU count | model of anaerobic species implant infection | 183 |
| (2) collect blood | ||||||
| (3) histology | ||||||
| pigs – Danish Landrace | stainless steel in tibia | S. aureus 4F9 (porcine) | 5 days | (1) collect blood | low-inoculum porcine model of implant infection | 184 |
| 1 × 102–1 × 104 CFU | (2) CT imaging | |||||
| pigs – Yorkshire-Landrace cross | none | S. aureus UAMS-1 | 11 and 15 days | (1) CFU count | pig model of hematogenous infection | 185 |
| 1 × 104 CFU | (2) collect blood | |||||
| (3) CT | ||||||
| (4) histology | ||||||