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. Author manuscript; available in PMC: 2022 Nov 28.
Published in final edited form as: ACS Infect Dis. 2021 Nov 11;7(12):3125–3160. doi: 10.1021/acsinfecdis.1c00465

Table 7.

Summary of Preclinical In Vivo Models from the Past Decade Used to Evaluate the Prevention of Orthopedic Implant-Associated Infections with Antimicrobial Biomaterials

models to evaluate prevention of implant-associated infections
animal model implant/location pathogen antimicrobial agent study duration key evaluation summary reference
mice – BALB/C titanium in femur S. aureus Xen 29 none 4 weeks (1) collect blood hydroxyapatite coating with ionic silver to prevent implant infections 186, 187
1 × 108 CFU (2) in vivo BLI
(3) histology
mice – BALB/C stainless steel in femur MRSA ATCC 43300 linezolid and MR-5 bacteriophage (local, sustained) 3 weeks (1) CFU count antibiotic and bacteriophage implant coatings for infection prevention 221
1 × 105–1 × 108 CFU (2) gait analysis
(3) histology
(4) X-rays
mice – BALB/C titanium in femur S. aureus ATCC 25923 none 2 weeks (1) SEM biofilm nanocomposite tantalum oxynitride-silver coating to prevent implant infection 222
5 × 105 CFU
mice – BALB/C silicon nitride in tibia MRSA USA 300 none 2 weeks (1) SEM biofilm role of surface topography of silicon nitride to prevent implant infection 38
1 × 105 CFU (2) histology
mice – C57Bl/6 stainless steel tibia S. aureus ATCC 43300 none 2 weeks (1) micro-CT aspirin to facilitate healing of implant infections 223
1 × 106 CFU (2) histology
mice – C57Bl/6 stainless steel in L4 spine and femur S. aureus Xen 36 vancomycin, tigecycline (local, sustained) 4 and 6 weeks (1) CFU count PEG-poly(propylene sulfide) coating to prevent implant infections 90–92
1 × 103 CFU (2) in vivo BLI
(3) X-rays
mice – C57Bl/6 stainless steel or titanium in femur S. aureus Xen 36 vancomycin, daptomycin, tigecycline (systemic) 1 week (1) CFU count model to compare efficacy of prophylactic antibiotics for implant infections 188
1 × 104 CFU (2) X-rays
(3) in vivo BLI
(4) SEM biofilm
mice – Lys-EGFP stainless steel in femur S. aureus ALC-2906 rifampin, minocycline (local, sustained) 2 weeks (1) CFU counts antibiotic polyesteramide coating to prevent implant infections 93
5 × 102 CFU (2) in vivo BLI
(3) histology
(4) SEM biofilm
mice – Kunming titanium in femur MRSA USA 300 none 4 weeks (1) CFU count graphdiyne-titanium oxide nanofiber composite implant prevent implant infections 224
1 × 107 CFU (2) histology
(3) SEM
rats – Sprague–Dawley stainless steel in tibia S. aureus ATCC 49230 gentamicin (local, sustained) 6 weeks (1) CFU count gentamicin in poly(d-l-lactide) coating to prevent implant infections 94–96
1 × 102– 1 × 103 CFU (2) collect blood
(3) X-rays
(4) histology
rats – Sprague–Dawley titanium in femur S. aureus ATCC 25923 none 6 weeks (1) micro-CT dimethylaminododecyl methacrylate and hydroxyapatite coated implant to prevent infection and promote osteogenesis 225
1 × 108 CFU (2) histology
(3) biocompatibility
rats – Sprague–Dawley magnesium and titanium in femur MRSA ATCC 43300 none 8 weeks (1) CFU count magnesium to prevent MRSA implant infections 226
1 × 106 CFU (2) X-rays
(3) micro-CT
(4) SEM of biofilms
rats – Sprague–Dawley titanium in femur S. aureus ATCC 29213 none 4 weeks (1) CFU counts layer-by-layer coating (silver nanoparticles + poly-l-glutamic acid and polyallylamine to prevent implant infection 227
1 × 106 CFU (2) micro-CT
(3) histology
rats – Sprague–Dawley titanium in femur S. aureus ATCC 49230 gentamicin palmitate (local, sustained) 6 weeks (1) CFU count antibiotic coated implant for infection prevention 228
1 × 102 CFU (2) X-rays
(3) collect blood
(4) histology
rats – Sprague–Dawley TiAl6V4 in tibia S. aureus ATCC 49230 gentamicin (local, sustained) 4 weeks (1) CFU count antibiotic coated titanium oxide implant for infection prevention and osseointegration 229
1 × 104 CFU (2) X-rays
(3) histology
rats – Sprague–Dawley titanium in femur S. aureus ATCC 25923 none 1–12 weeks (1) CFU count poly(glycidyl methacrylate) and quaternized poly (ethylene imine) functionalized titanium implants with alendronate for infection prevention and osseointegration 122
1 × 109 CFU (2) micro-CT
(3) histology
(4) pull-out test
rats – Sprague–Dawley titanium in tibia S. aureus ATCC 25923 none 4 weeks (1) CFU count poly-l-lysine functionalized implants for infection prevention and osseointegration 230
1 × 104 CFU (2) micro-CT
(3) histology
rats – Sprague–Dawley titanium in femur S. aureus ATCC 25923 gentamicin (local, sustained) 6 weeks (1) CFU count antibiotic nanotube implants for infection prevention and osseointegration 231
1 × 105 CFU (2) X-rays
(3) histology
rats – Sprague–Dawley poly(ether ether ketone) in tibia S. aureus Xen 29 gentamicin (local, sustained) 1–8 weeks (1) CFU count nanolayered antibiotic and bone morphogenic protein-2 implant coating for infection prevention and osseointegration 97
5 × 105 CFU (2) micro-CT
(3) histology
(4) pull-out testing
rats – Sprague–Dawley titanium in femur S. aureus ATCC 29213 none 1 week (1) CFU count hydrophobic triethoxysilane implant coating for infection prevention 232
1 × 106 CFU (2) histology
rats – Sprague–Dawley PMMA in femur MRSA clinical teicoplanin (local, sustained) 3 weeks (1) CFU count antibiotic and calcium sulfate PMMA to prevent implant infections 129
1 × 108 CFU (2) X-rays
(3) histology
rats – Sprague–Dawley stainless steel in femur S. aureus ATCC 43300 none 6 weeks (1) micro-CT sodium butyrate modified implant to mitigate infection and promote osteogenesis 112
1 × 104 CFU (2) histology
rats – Sprague–Dawley copper-poly(ether ether ketone) in femur MRSA ATCC 43300 none 4 weeks (1) CFU count composite implant to prevent MRSA infection 114
1 × 106 CFU (2) micro-CT
(3) histology
(4) biocompatibility
rats – Sprague–Dawley poly(ether ether ketone) in femur S. aureus ATCC 6538 gentamicin (local, sustained) 4–6 weeks (1) X-rays antibiotic composite implant to promote osseointegration and prevent infection 113
1 × 104 CFU (2) micro-CT
(3) histology
rats – Sprague–Dawley gallium–strontium magnesium alloy in femur S. aureus ATCC 43300 none 5 days (1) CFU count metal alloys for intrinsic prevention of implant infections 233
1 × 105 CFU (2) histology
(3) SEM
rats – Sprague–Dawley Pro Osteon 500R + PEG + poly (capro-lactone) + PLGA in tibia S. aureus ATCC 49230 rifampin, vancomycin (local, sustained) 10 weeks (1) CFU count antibiotic putty to prevent implant infection 98
1 × 108 CFU (2) X-rays
(3) micro-CT
(4) histology
rats – Sprague–Dawley 3D printed titanium in tibia S. aureus ATCC 49230 vancomycin (local, sustained) 4 weeks (1) CFU count chitosan silver particle antibiotic implant coatings to prevent infection 99
1 × 106 CFU (2) micro-CT
(3) collect blood
(4) histology
rats – Wistar titanium in femur S. aureus Xen 40 none 6 weeks (1) CFU count vitamin E phosphate coating to improve implant integration 189
3 × 104 CFU (2) collect blood
(3) micro-CT
(4) histology
(5) in vivo BLI
rats – Wistar Ti6Al4V in tibia S. aureus ATCC 25923 none 6 weeks (1) CFU count hydroxyapatite and silver coated implant infection model 234
1 × 102–1 × 103 CFU (2) X-rays
(3) histology
rabbits – Dutch Belted titanium in femur S. aureus SAP231 linezolid, rifampin (local, sustained) 1 week (1) CFU count PLGA and poly(caprolactone) nanofiber coated implant infection model 100
1 × 104 CFU (2) in vivo BLI
rabbits – New Zealand White stainless steel in tibia MRSA ATCC 43300 none 6 weeks (1) micro-CT titanium with nanothick calcium oxide MRSA implant infection model 246
1 × 104 CFU (2) histology
rabbits – New Zealand White titanium in femur MRSA ATCC 43300 none 6 weeks (1) CFU count silver ion calcium phosphate ceramic nanopowder implant coating infection model 150
5 × 102 CFU (2) X-rays
(3) histology
rabbits – New Zealand White Porous tantalum in radius S. aureus ATCC 49230 tobramycin (local, sustained) 2 weeks (1) X-rays antibiotic PLGA microspheres in porous implant to prevent infections 101
2 × 106 CFU (2) histology
rabbits – New Zealand White titanium in tibia S. aureus ATCC 10832 tobramycin (local, sustained) 4 weeks (1) CFU count antibiotic-periapatite coated implants to prevent infection and promote osseointegration 236
1 × 103–1 × 105 CFU (2) collect blood
(3) histology
(4) erythrocyte sedimentation rate
rabbits – New Zealand White stainless steel in humerus S. aureus JAR 060131 gentamicin (local, sustained) 1 week (1) CFU count injectable antibiotic thermoresponsive hyaluronic acid implant coating to prevent infections 23
2 × 106 CFU (2) X-rays
(3) collect blood
(4) histology
rabbits – New Zealand White titanium and stainless steel in humerus S. aureus JAR 060131 none 4 weeks (1) CFU count impact of implant topography on infection prevention 237
2 × 103–2 × 105 CFU (2) X-rays
rabbits – New Zealand White titanium in femur MRSA clinical isolate vancomycin (local, sustained) 12 weeks (1) CFU count antibiotic hydrogel implant coating for infection prevention 102
5 × 104–5 × 106 CFU (2) collect blood
(3) histology
rabbits – New Zealand White titanium in femur S. aureus ATCC 6538P none 1 week (1) CFU count antimicrobial fusion peptide implant coating for infection prevention and osseointegration 238
1 × 108 CFU (2) micro-CT
(3) histology
rabbits – New Zealand White titanium in tibia S. aureus ATCC 25923 none 4 weeks (1) CFU count molybdenum disulfide/polydopamine – RGD implant coating for infection prevention 239
2 × 103 CFU (2) micro-CT
(3) histology
rabbits – New Zealand White Ti6Al4V in femur MRSA ATCC 43300 none 10 weeks (1) CFU count silver and ceramic implant coating for infection prevention 157
5 × 104 CFU (2) collect blood
(3) histology
rabbits – New Zealand White magnetic iron oxide particles with carbon nanotubes in tibia MRSA CCTCC 16465 gentamicin (local, sustained) 2 weeks (1) CFU count bacterial capturing implant infections with magnetic microwave activated composites 26
1 × 106 CFU (2) collect blood
(3) histology
(4) MRI
rabbits – New Zealand White calcium phosphate in tibia S. aureus Xen 29 tobramycin (local, sustained) 4 weeks (1) CFU count antibiotic calcium phosphate for prevention of implant infections 190
1 × 107 CFU (2) collect blood
(3) X-rays
(4) histology
rabbits – New Zealand White chitosan and calcium phosphate in tibia S. aureus moxifloxacin (local, sustained) 4 weeks (1) CFU count composite antibiotic material for prevention of implant infection 240
1 × 106 CFU (2) histology
sheep stainless steel in tibia S. aureus ATCC 6538 cefazolin (local, sustained) 7 days (1) CFU count antibiotic filled steel implants for infection prevention in sheep 241, 242
6.6 × 106 CFU (2) collect blood
(3) histology
(4) antibiotic distribution
sheep – Rambouillet titanium in femur MRSA clinical trialkyl norspermidine-biaryl (local, sustained) 4 and 24 weeks (1) CFU count antimicrobial compound active release implant coating for infection prevention 243
2 × 108 CFU (2) X-rays
(3) SEM
(4) histology
sheep – Columbia Cross hydroxyapatite calcium carbonate and PLGA in femur S. aureus ATCC 49230 tobramycin (local, sustained) 12 weeks (1) CFU count antibiotic bone void filler to prevent implant infection 103
5 × 105 CFU (2) collect blood
(3) micro-CT
(4) histology
sheep – Dorset Cross titanium plate in tibia S. aureus ATCC 25923 vancomycin (local, sustained) 12 weeks (1) CFU count antibiotic modified implant surface to prevent infection 244
2 × 106 CFU (2) X-rays
(3) SEM biofilm
(4) histology
(5) gait analysis
sheep – English Mule PLGA and PEG in femur S. aureus F2789 gentamicin, clindamycin (local, sustained) 2 and 13 weeks (1) CFU count injectable and biodegradable antibiotic gel to prevent implant infection 104
2 × 106 CFU (2) collect blood
(3) micro-CT
(4) histology
goat stainless steel in tibia S. aureus ATCC 25923 none 5 weeks (1) X-rays titanium oxide and siloxane implant coating to prevent infection 245
2 × 104 CFU (2) micro-CT
(3) histology
(4) silver and titanium in organs
goat – Spanish PMMA and calcium sulfate in tibia S. aureus ATCC 29213 tobramycin (local, sustained) 3 weeks (1) CFU count evaluation of ability of commercial antibiotic composites for prevention of implant infection 130
2 × 106 CFU