Table 2.

Rat models of orthopedic infections.

Model/Strain	Gender	Age/Weight	Microorganism/ Concentration	Disease Model	Site of Inoculum	Osteomyelitis Induction	Timepoint	Aim of the Study	Results	Ref.
Inbred cr/rar and outbred Sprague–Dawley albino	M	Inbred: 200–400 g; Sprague–Dawley albino rats: 400–500 g	S. aureus phage type 52/52A/80. 3.0 × 106 CFU	CO	Tibia (bone marrow)	Sodium morrhuate 5% and arachidonic acid	35 days	To verify if arachidonic acid could facilitate experimental osteomyelitis	Arachidonic acid was a strong facilitator of osteomyelitis.	[159]
Sprague–Dawley albino	M	300–400 g	P. aeruginosa (field strain isolated from a patient with osteomyelitis). 2.4, 3.3, 4.8, 6.4, and 7.1 log CFU were used to determine ID50. Log 5.8 CFU was used for experimental inoculation.	CH	Tibial metaphysis		21 days (for ID50 determination) and 63 days for the experiment	To create a rat model of chronic P. aeruginosa osteomyelitis that did not require promoting agents	The ID50 was log 4.0 CFU with an ID100 of log 6.4. In the rat model, the establishment of P. aeruginosa osteomyelitis does not require promoting agents.	[176]
White	na	na	S. aureus	Mandibular osteomyelitis	Drilled cavity in mandibular cavity	na	na	To develop a reliable model of mandibular osteomyelitis	Preclinical study of new drugs and physiotherapeutic methods can be obtained after the used of this model	[170]
Wistar	F	180–220 g	S. aureus Phillips (field strains from osteomyelitis). 5 × 104, 5 × 106, 5 × 107, or 5 × 108 CFU (surgically exposed mandible). 5 × 106, 5 × 107, or 5 × 108 CFU (surgically exposed tibia). 5 × 106 and 5 × 107 CFU (control B and control C). 108 CFU (control D).	HO	Intramedullary injection of sodium morrhuate in mandible and tibia. Bacteria were injected into the femoral vein.	Sodium morrhuate 5%	14 days	To establish and evaluate a new rat model of haematogenous osteomyelitis	No pathologic changes were produced in animals undergoing only surgery but receiving sodium morrhuate (control). In the treated group, osteomyelitis was successfully established.	[171]
Sprague–Dawley	M	300 g	S. aureus ATCC 29213 or P. aeruginosa ATCC 27853. 103 CFU in one group and 106 CFU in the other for S. aureus and ascending concentrations for P. aeruginosa. 103 CFU of S. aureus, 103 CFU of P. aeruginosa, or 103 CFU of both S. aureus and P. aeruginosa.	Complex orthopaedic wounds	Lumbar spinous process	na	14 days	To determine whether synergy exists between S. aureus and P. aeruginosa in a rat model of complex orthopaedic wounds	When low levels of each organism were present in the wound, synergy existed. The ability of S. aureus to cause infections qis enhanced by low concentrations of P. aeruginosa.	[177]
Sprague–Dawley	F	5 months	S. aureus ATCC 49230. 103 CFU	Implant–related osteomyelitis	Proximal tibia metaphysis (medullary cavity)	Poly (D,L–lactide)–coated Kirschner wire	42 days	To test the efficacy of a new biodegradable, gentamicin–loaded poly(D,L–lactide) coating	The implant–related infection was significantly reduced by PDLLA + 10% gentamicin.	[166]
Sprague–Dawley	F	250–300 g	S. aureus Xen29 (genetically engineered using Gram–positive lux transposon plasmid pAUL–Atn 4001 luxABCDE kmr). 106 CFU/mL. Biofilm–coated K–wire (0.5 cm long).	Implant–related osteomyelitis (biofilm model)	Proximal anterior margin of the tibial epicondyle	Arachidonic acid (50 µg/mL in 0.9% NaCl solution)	10 days	To investigate photodynamic therapy (PDT) as alternative treatment for osteomyelitis using bioluminescence	1 mM of 5–aminolevulinic acid and methylene blue 0.1 mM can mediate the sensitivity of S. aureus at 5 J cm−2 light dose with ≥4log10 cell kill	[167]
Sprague–Dawley	na	417 g	S. epidermidis ATCC 35984. 105 CFU/cavity	Implant–related infection	Cortex of the intercondylar notch of the femur	na	14 days (control group), 56 days (treated groups)	To evaluate the effect of serratiopeptidase in the eradication of periarticular hardware	Bacterial growth was reduced in the treated group by serratiopeptidase and antibiotic together compared to animals inoculated with antibiotics alone	[178]
Wistar	M	12–14 weeks, 423–481 g	S. aureus ATCC 29213. 107 CFU	Implant–associated infection	Femoral medullary cavity	na	21 days	To assess the antibiotic efficacy of moxifloxacin in implant–associated infections	Animal mortality 0%. The efficacy of moxifloxacin was significantly greater (p < 0.01) than that of vancomycin.	[172]
Wistar	na	300–350 g	S. aureus ATCC 29213. 107 CFU	Implant–related chronic osteomyelitis	Medullary cavity of femur	na	28 days	To test moxifloxacin compared to teicoplanin in chronic implant–related osteomyelitis	For moxifloxacin–group compared to teicoplanin–group the decrease of bacterial counts was more prominent (p = 0.001).	[169]
Sprague–Dawley	M	250–300 g	S. aureus (field strain isolated from a patient with an infected total hip arthroplasty). 104 CFU	Femur fracture model	Medullary cavity of femur	na	21 days	To develop a model of induced implant–associated osteomyelitis following fracture repair	Between the control and S. aureus group, by one week after surgery/inoculation, significant differences in the radiographic score for osteomyelitis were detected.	[137]
Sprague–Dawley	M	10–w, 283–401 g	Methicillin–resistant S. aureus (field strain isolated from a patient with septicemia). 1.0 × 102 CFU	Implant–related osteomyelitis	Tibial medullary cavity	na	28 days	To develop an antibacterial coating with Ag–containing hydroxyapatite (Ag–HA)	Antibacterial activity of Ag–HA coating was shown against MRSA. Serum Ag ion concentrations reached a peak at about 48 h	[168]
Sprague–Dawley	F	na	S. aureus ATCC 25923. 106, 105, 104 and 103 CFU	Implant–associated infection	Medial proximal tibial metaphysis	na	42 days	To evaluate a novel animal model for the generation of implant–associated infections in the tibial metaphysis of rats	A higher viable count was observed in peri–implant bone samples from animals inoculated with 106 CFU. However, there could be no correlation between initial load and concentration after sacrifice.	[174]
Sprague–Dawley	M	12 w	S. aureus DSM 28763 (field strain isolated from wound infection; genome sequenced, biofilm producer). 103 CFU	Implant–related infection	Tibia	na	42 days	To determine if the prophylactic administration of TLR9 ligand CpG ODN type B would affect a model of implant–related chronic infection	Results indicated that the bacterial load in the infected tibia was reduced at the beginning of infection but failed to prevent the development of chronic infection.	[179]
Wistar	M	12 weeks, 300–350 g	Methicillin–resistant S. epidermidis strain GOI1153754–03–14 (field strain from infected knee prosthesis). 1 × 103, 1 × 105 and 1 × 108 CFU/rat	Fracture model	Non–critical midshaft full–thickness defect in femur	na	56 days	To understand the role of subclinical bacterial contaminations in the non–union development	Bone healing was prevented in low–grade S. epidermidis contamination. Bacterial inoculum and non–union rate followed a dose–dependent relation	[114]
Wistar	M	5 months, 353–401 g	S. aureus ATCC25923. 102 CFU (Group I–IIA), 103 CFU (Group I–IIB)	Implant–related osteomyelitis	Proximal lateral tibial metaphysis	na	42 days	To evaluate a low bacterial inocula animal model of tibial metaphysis and investigate osseointegration of the implants coated with hydroxyapatite (HA) and low–dosed HA–silver (HA–Ag)	No systemic infection registered. Infection was induced, independently whether bacterial load used and implant inserted.	[173]
Sprague–Dawley	M	350–400 g	S. aureus Xen 29 ATCC 12600. 2 × 107 CFU (injected in 8 mm length–hole), 8 × 107 CFU (injected into the joints)	Periprosthetic joint infection	Lateral femoral condyle	na	28 days	To develop a joint replacement model with ultrahigh molecular weight polyethylene (UHMWPE) and titanium components	Clinical infection indicators such as osteolysis, loosening of the implants were observed for 4 weeks	[175]

Abbreviation: na = not available