Table 6.

Summary of Preclinical In Vivo Models from the Past Decade Used to Evaluate the Antimicrobial Activity and Properties of Implanted Biomaterials for Orthopedic Implant-Associated Infection Applications

models to evaluate antimicrobial activity/properties of implanted materials
animal model	implant/location	pathogen	antimicrobial agent	study duration	key evaluation	summary	ref
mice – BALB/C	magnesium in subcutaneous pouch	P. aeruginosa PAO1 CTX::lux	none	8 days	(1) CFU count	degradable magnesium implant to modulate host immune response	59
					(2) histology
					(3) in vivo BLI
					(4) SEM biofilm
mice – BALB/C	polyester-poly urethane in subcutaneous pouch	S. aureus Xen 29	levofloxacin (local, sustained)	4 weeks	(1) CFU count	antibiotic polymer coatings to prevent implant infections	87
		1 × 106 CFU			(2) activity of residual drug in implant
mice – BALB/C	polyethylene terephthalate in subcutaneous pouch	P. aeruginosa PsAer-9	none	1 week	(1) in vivo fluorescence	near-infrared fluorescence probes to image implant inflammation and infection	37
					(2) CFU count
mice – C57B1/6	PEG hydrogel in femur	S. aureus UAMS-1	none	1 and 5 weeks	(1) CFU count	lysostaphin hydrogels to prevent implant infections	120
		1.55 × 108 CFU			(2) micro-CT
		S. aureus USA 300			(3) histology
		3.43 × 108 CFU
mice – C57B1/6	none	MRSA USA 300 1 × 106 CFU	None	2 weeks	(1) micro-CT	poly(propylene sulfide) nanoparticles to prevent implant infections	198
					(2) histology
					(3) in vivo BLI
rats – Sprague–Dawley	chitosan sponge in subcutaneous pouch	none	vancomycin, ciprofloxacin, cefuroxime (local, sustained)	6 weeks	(1) collect blood	degradable antibiotic chitosan sponges to prevent implant infections	83
					(2) HPLC detect drug in plasma
					(3) in vivo degradation
					(4) tissue drug concentration
rats – Sprague–Dawley	micropatterned silicone in subcutaneous pouch	S. aureus ATCC 6538	none	<1 week	(1) CFU count	micropatterned implant to prevent implant infection	41
		1 × 104 CFU
rats – Sprague–Dawley	silicone in subcutaneous pouch	S. aureus ATCC 29213	none	1–2 weeks	(1) CFU count	nitric oxide releasing implant coatings to prevent implant infection	135
		1 × 108 CFU			(2) SEM biofilm
					(3) histology
rats – Sprague–Dawley	silver hydroxyapatite coated titanium in subcutaneous pouch	MRSA UOEH6	none	1 week	(1) quantify biofilm	composite implant coating to mitigate biofilm	148
		10 × 108 CFU
rats – Sprague–Dawley	Eudragit particle coated Ti6Al4V in subcutaneous pouch	none	vancomycin (local, sustained)	1 week	(1) collect blood	antibiotic coated implant to prevent infection	161
					(2) LC-MS detect drug in serum
rats – Wistar	hydroxyapatite/calcium sulfate in subcutaneous pouch	none	rifampin (local, sustained)	4 weeks	(1) collect blood	antibiotic bioactive ceramic for treating implant infections	144
					(2) HPLC detect drug in serum and bone
rats – Wistar	titanium in tibia	none	none	1–4 weeks	(1) histology	hydroxyapatite and metal coating for promoting implant osseointegration	147
					(2) X-rays
					(3) forced swimming test
rats – Wistar	stainless steel in femur	S. aureus ATCC 29213	vancomycin, moxifloxacin (systemic)	3 weeks	(1) collect blood	evaluation of tissue concentration of antibiotics for prevention of implant infection	196
		1 × 108 CFU			(2) HPLC detect drug in serum
					(3) minimum inhibitory concentration drugs
rabbits – New Zealand White	Ti6Al4V in femur	P. aeruginosa Pa11	none	5 weeks	(1) CFU count	method to detect presence of implant infection through urine with biomaterials	40
		1 × 106 CFU			(2) X-rays
					(3) histology
					(4) micro-CT
					(5) measure Al in urine
rabbits – New Zealand White	calcium sulfate in tibia	none	gentamicin, vancomycin, tobramycin (local, sustained)	4–12 weeks	(1) X-rays	calcium sulfate to promote osseointegration of implants	141
					(2) micro-CT
					(3) histology
rabbits – New Zealand White	calcium sulfate in tibia	none	vancomycin (local, sustained)	4 weeks	(1) collect blood	calcium sulfate with bone morphogenic protein-2 to promote osseointegration and prevent implant infection	143
					(2) HPLC detect drug in serum and bone
					(3) histology
rabbits – New Zealand White	calcium sulfate in tibia	none	gentamicin, vancomycin, tobramycin (local, sustained)	4 weeks	(1) X-rays	antibiotic calcium sulfate to prevent implant infection	142
					(2) collect blood
					(3) HPLC detect drug in serum and bone
rabbits – New Zealand White	calcium phosphate granules in tibia	MRSA clinical	vancomycin, tobramycin (local, sustained)	4 weeks infection	(1) CFU count	biodegradable antibiotic cement for treatment of MRSA implant infection	197
		5 × 107 CFU		6 weeks antibiotics	(2) X-rays
					(3) SEM
					(4) histology
					(5) HPLC detect drug