Table 4.

More investigations on the types of scaffolds as delivery systems of antimicrobial agents for the management of osteomyelitis.

Types of Scaffolds	Antimicrobial agents	Carriers	Achievements	Study type/ assayed model	References
Metal implants	Gentamicin	Titanium implant	High prophylaxis against implant-related osteomyelitis	In-vivo/Rats	(Diefenbeck et al., 2016)
	Vancomycin	Zeolitic imidazolate nanocrystals	Sustained release of antibiotic Eradication of infection Promotion of osteogenesis	In-vitro	(Karakeçili et al., 2019)
		3D printed Titanium implant	High loading of vancomycin on the implant Sustained release Promotion of osteogenesis	In-vivo/ Rabbits	(Zhang et al., 2020)
	Clindamycin	3D printed coatings on titanium and stainless steel implant	Sustained release of antibiotic for 3 days	In-vitro	(Maver et al., 2021)
Bioceramics	Vancomycin	Hydroxyapatite/ Calcium phosphate	Successful management of diabetic foot infection.	Clinical/ Patients	(Karr, 2011)
		Hydroxyapatite/ Calcium phosphate	Controlled antibiotic release pattern over a 12-day period.	In-vitro	(Thanyaphoo & Kaewsrichan, 2012)
		Hydroxyapatite/ Poly amino acid	Significant bactericidal activity Sustained duration of action for 42 days in-vivo.	In-vivo/Rabbits	(Cao et al., 2016)
		Hydroxyapatite	Increased drug loading in the freeze-gelated matrix -Sustained release up to 5 days.	In-vitro	(Hess et al., 2016)
		Hydroxyapatite	High antibiotic loading Sustained release from the implant.	In-vitro	(Parent et al., 2016)
		Calcium polyphosphate	Sustained release of the antibiotic.	In-vitro	(Comeau & Filiaggi, 2017)
		Calcium phosphate/ calcium sulfate	New bone formation. Low rates of infection recurrence in 31 patients with chronic osteomyelitis.	Clinical/ Patients	(Zhao et al., 2020)
	Gentamicin	Calcium sulfate	Significant bactericidal activity of the scaffold.	In-vitro	(Thein et al., 2013)
		Hydroxyapatite/ Calcium phosphate	Clinical cure of the heel ulcers in diabetic foot patients after 16 weeks without need of amputation.	Clinical/ Patients	(Drampalos et al., 2018)
	Vancomycin/gentamicin	Calcium sulfate	Full recovery in 4 months in a patient with diabetic foot infection.	Clinical/ Patients	(Morley et al., 2016)
		Calcium sulfate/ hydroxyapatite	Prevention of biofilm formation	In-vitro	(Bidossi et al., 2020)
	Ceftriaxone/sulbactam	Bioactive glass	Sustained antibiotic release for up to 42 days in the treated animals. New bone formation.	In-vivo/Rabbits	(Kundu et al., 2011)
	Gatifloxacin/ fluconazole	Bioactive glass	Sustained antibiotic release for up to 6 weeks.	In-vitro	(Soundrapandian et al., 2011)
	Vancomycin/ rhBMP-2	Calcium sulfate	Sustained release in-vivo for up to 14 to 21 days. -Formation of new bone.	In-vivo/Rabbits	(Wang et al., 2011)
	Ceftriaxone/sulbactam	Hydroxyapatite	New bone formation Sustained drug release for 42 days.	In-vivo/Rabbits Clinical/ Patients	(Bhattacharya et al., 2013)
	Linezolid	Calcium deficient apatite (CDA)	Enhanced efficacy of treatment with IV treatment.	In-vivo/Rabbits	(Gaudin et al., 2013)
	Amphotericin B/ voriconazole	Hydroxyapatite/ Calcium sulfate	Maintained effective antifungal concentrations over 96 hours.	In-vitro	(Karr & Lauretta, 2015)
	Levofloxacin	Bioactive glass/ HA nanoparticles	Sustained with pH-dependent release of drug at the infection site.	In-vitro	(Cicuéndez et al., 2018)
	Sitafloxacin/ rifampin	Calcium phosphate	Decreased bacterial colonization Formation of new bone in osteomyelitis model	In-vivo/ Mice	(Trombetta et al., 2019)
	Rifampicin	Nanohydroxyapatite /calcium sulfate	Sustained release for 28 days Eradication of infection New bone formation	In-vivo/Rats	(Qayoom et al., 2020)
Polymeric	Gentamicin	PMMA	Effective treatment of patients with infected nonunioun of the long bones.	Clinical/ Patients	(Selhi et al., 2012)
	Gentamicin/silver ion	Silk fibrin	Effective inhibition of MRSA growth Stimulation of bone regeneration	In-vivo/Rats	(Zhang et al., 2019b)
	Vancomycin/rifampin	Polydioxanone	Inhibition of biofilm formation.	In-vitro	(Waeiss et al., 2014)
	Vancomycin/cefuroxime	PMMA	Successful treatment of the infection in 7 cases with chronic osteomyelitis.	Clinical/ Patients	(Bharti et al., 2016)
	Gentamicin,vancomycin, amikacin, ceftriaxone	PMMA	Effective inhibition of MRSA growth for 42 days	In-vitro	(Noor et al., 2016)
	Vancomycin	PMMA	Prolonged release of the antibiotic from the bone cement over 6 weeks in femoral osteomyelitis model.	In-vivo/Rats	(Oh et al., 2016)
		Chitosan	Sustained release for 26 days Promotion of osteoblast formation	In-vivo/Rabbits	(Tao et al., 2020)
	Fosfomycin	Chitosan	Sustained release for 5 days Eradication of infection	In-vitro	(Tucker et al., 2021)
	Linezolid/daptomycin /vancomycin	PMMA/ PLGA microparticles	Synergistic effect of the antibiotics Sustained drug release for 2 months.	In-vitro	(Parra-Ruíz et al., 2017)
	Vancomycin/amikacin	Chitosan sponge	Prevention and clearance of polymicrobial implant associated-biofilm.	In-vivo/ Mice	(Boles et al., 2018)
	Ciprofloxacin	Poly (hydroxyethyl methacrylate)	Sustained antibiotic release for 5 days Osteoblast differentiation and osteoinduction	In-vitro	(Sreeja et al., 2020)
	Rifampicin	PCL	Sustained antibiotic release for 14 days	In-vitro	(Lee et al., 2020)
Composite	Vancomycin	PLLA/ β TCP	Achieved controlled release of antibiotic. Formation of new bone.	In-vivo/Rats	(Kankilic et al., 2014)
		Hydroxyapatite/ collagen	Controlled release of antibiotic Eradication of bacteria Induction of new bone formation	In-vitro	(Coelho et al., 2015)
		Calcium sulfate / PMMA	Effective control of infection in patients with chronic osteomyelitis Providing high concentrations at the infection site.	Clinical/ Patients	(Luo et al., 2016)
		Gelatin/ β TCP	Extended release of antibiotic from scaffold for 8 weeks -Healing of the bone defect. Eradication of infection.	In-vivo/Rabbits	(Zhou et al., 2018)
		PLA/ nanohydroxyapatite	Sustained antibiotic release Stimulation of bone regeneration	In-vitro	(Zhao et al., 2019)
		Nano- hydroxyapatite / Gelatin / PLA	Significant bacterial reduction in osteomyelitis rat femur model. Formation of new bone.	In-vivo/Rats	(Krishnan et al., 2020)
		Heparinized nanohydroxyapatite/collagen	Sustained release for 19 days Eradication of infection	In-vitro	(Padrão et al., 2021)
		Polyurethane/ hydroxyapatite	Reduced number of bacteria in the bone Had the ability of bone regeneration	In-vivo/Rabbits	(Beenken et al., 2021)
		Hydroxyapatite/ Sodium alginate/ chitosan	Eradication of infection Had osteogenic properties	In-vitro	(Liu et al., 2021)
	Gentamicin	Hydroxyapatite/ collagen	Sustained release of antibiotic for 3 days Prevention of implant-associated infection	In-vitro	(Oshima et al., 2020)
	Ceftriaxone	Hydroxyapatite/ β TCP /chitosan	Prolonged release pattern for more than 5 weeks.	In-vitro	(Kundu et al., 2010)
	Moxifloxacin	Chitosan/ calcium phosphate	Controlled release for 3 days. Induction of osteogenesis	In-vivo/Rabbits	(Radwan et al., 2020)
		Poly-lactide-co-ε-caprolactone/calcium phosphate	Sustained release for 6 weeks Enhanced cellular proliferation and differentiation Diminished sequestrum formation and inflammation	In-vivo/Rabbits	(Radwan et al., 2021)
	Gatifloxacine	β TCP/ PLGA	Osteoconductive scaffolds with efficacy in local treatment of osteomyelitis.	In-vivo/Rabbits	(Tamazawa et al., 2011)
	Rifampicin/ ciprofloxacin	PCL/ β TCP	Good therapeutic activity against the causative bacteria -Sustained drug release.	In-vitro	(Ahola et al., 2012)
	Gentamicin/ vancomycin	PMMA/ β TCP	Eradication of infection through custom made devices in femoral osteomyelitis model.	In-vivo/Rabbits	(Giavaresi et al., 2012)
	Daptomycin	Calcium phosphate / chitosan	Prolonged the duration of release of the antibiotic Maintaining high concentrations of the antibiotic -Better therapeutic outcome following surgical debridement.	In-vivo/Rabbits	(Beenken et al., 2014)
	Ciprofloxacin	Gelatin/ hydroxyapatite	Sustained release of the antibiotic for 60 days. -enhancing of osteogenic differentiation in cells	In-vitro	(Krishnan et al., 2015)
		Hydroxyapatite/ PCL	Controlled the release of antibiotic in implant.	In-vitro	(Nithya & Sundaram, 2015)
	Rifapentine	Hydroxyapatite/ Poly amino acid	Inhibition of bacterial growth. Sustained antibiotic release and cure of chronic osteomyelitis after 12 weeks.	In-vivo/Rabbits	(Yan et al., 2015)
	Tobramycin	PCL/ PEG/ Calcium phosphate/ Hydroxyapatite	Osteoconductivity and resorbtion with sustained antibiotic release.	In-vivo/Rabbits	(Jones et al., 2016)
	Doxycycline	Bioactive glass/ mesoporous silica	Sustained release for 19 days Eradication of infection	In-vitro	(Szewczyk et al., 2021)
	Silver ion	Nano- hydroxyapatite / polyurethane	Controlled release of silver ion, Eradication of infection. Formation of new bone.	In-vivo/Rabbits	(Zhang et al., 2019a)