Table 2.

Chitosan-based delivery systems and scaffolds in in vivo wound healing and skin damage models intended for localized antimicrobial therapy.

Delivery System/Scaffold	System	Microorganisms	Findings	Ref.
	MW
	DDA
Particles and carriers	CNPs: Chitosan 50–190 KDa DDA: 75–85% Antimicrobial peptide LL-37	MRSA	MRSA-infected wound model in mice: No growth of MRSA was observed in the group treated with LL-37 loaded CNPs after 7 days. This antibacterial effect was superior to all other treatment conditions.	[64]
	CNPs: Chitosan 50–190 kDa DDA: n.a. Cefadroxil	S. aureus	S. aureus-infected wound model in rats: CNPs loaded with cefadroxil embedded in in situ poloxamer 407 hydrogel showed a significant reduction in the bacterial burden in the wounds and complete healing after 5 days.	[184]
	CNPs: Chitosan LMW DDA: 75–85% Vancomycin hydrochloride	MRSA	MRSA-infected wound model in mice: the rats treated with pH-responsive CNPs comprising gemini surfactants loaded with vancomycin displayed a significantly reduced bacterial burden compared with both drug-free CNPs and free vancomycin.	[185]
Excipient and coatings	Beads: Chitosan MW: n.a. DDA: 90% Zinc oxide NPs		Noninfected wound model in mice: The bacterial growth in the wound without induced infections treated with any of the chitosan/PVA/zinc beads was lower than the control. Almost no growth was observed in mice treated with chitosan, chitosan/PVA, or the loaded beads.	[176]
	Chitosan-functionalized graphene quantum dots: Chitosan oligosaccharide MW: n.a. DDA: n.a. Graphene quantum dots	S. aureus	S. aureus-infected wound model in rats: the rats treated with the chitosan-functionalized quantum dots composite together with illumination exhibited improved wound healing compared to all the other groups.	[186]
Polymer-based gels	Hydrogel: Chitosan LMW DDA: >85% Terbinafine hydrochloride	C. albicans	C. albicans-infected wound in rats: chitosan hydrogel loaded with vesicles comprising penetration enhancers produced a significant reduction of C. albicans in the wound bed.	[187]
	Hydrogel: Cyclodextrin-modified chitosan 15–22 kDa DDA: 75−80% Diclofenac Silver ions	P. aeruginosa	P. aeruginosa-infected wound in a murine model: β-cyclodextrin modified chitosan supramolecular hydrogel loaded with diclofenac and silver ions displayed improved wound healing and reduced the bacterial load in the wound bed.	[188]
	Hydrogel: Chitosan MW: n.a. DDA: ≥95% Silver nitrate Calcium sulfate dehydrate Zinc nitrate hexahydrate Copper nitrate trihydrate	S. aureus	S. aureus-infected wound model in mice: The chitosan/ion hydrogel in gauzes surpassed chitosan alone and the control group in wound healing. Additionally, the group treated with the chitosan/ion hydrogel in gauzes significantly reduced bacterial load in the wound bed compared with chitosan alone.	[189]
	Hydrogel: Chitosan 300–450 kDa DDA: 85–95% Silver sulfadiazine	S. aureus	S. aureus-infected burn and wound model in mice: The healing rate of the wounds treated with the silver sulfadiazine nanocrystal in the hydrogel was faster, and the overall healing was superior to a cream formulation in both the burn and wound model.	[190]
	Hydrogel: Chitosan MW: 100−150 kDa DDA: 85% Ciprofloxacin Fluconazole	S. aureus E. coli C. albicans	Polymicrobial wound model in rats: The ciprofloxacin and fluconazole-loaded fibrin NPs loaded in chitosan hydrogel bandage displayed a significant reduction in microbial load in the infected wound compared to the unloaded- fibrin NPs loaded in chitosan. However, there was still some microbial growth after 14 days.	[191]
	Hydrogel: Chitosan (maleic anhydride grafted chitosan) MW: n.a. DDA: n.a. Antimicrobial peptide Hydrogen peroxide	MRSA	MRSA biofilm-infected wound model in mice: The hydrogel loaded with antimicrobial peptide and hydrogen peroxide displayed a significant reduction in bacterial viability compared to all other treatments; however, not complete eradication. Chitosan alone reduced bacterial viability. Wound closure also improved in the groups treated with the coloaded hydrogel.	[192]
Scaffolds	Film: Chitosan 50–190 kDa DDA: 75–85% S-nitrosoglutathione	MRSA	MRSA biofilm-infected wound model in mice: Both loaded and unloaded chitosan films reduced the bacterial burden in the wound and improved the healing rate compared to the control group. However, the NO-releasing film displayed a significantly improved healing and dispersal of the biofilm.	[193]
	Film: Chitosan 200 kDa DDA: 85% Catechol	MRSA	MRSA-infected wound model in rats: The bacterial load in the group treated with the catechol-chitosan film at a reduced state was significantly reduced compared with the other groups. Additionally, the tissue in this group appeared normal.	[194]
	Film: Chlorinated chitosan MMW DDA: 75–85% Chloramine	MRSA	MRSA-infected wound model in mice: Chlorinated chitosan film produced with electrofabrication induced faster wound healing and reduced the wound’s bacterial burden, compared to the control and plain chitosan.	[195]
	Membrane: Chitosan MW: n.a. DDA: 87% Silver sulfadiazine	P. aeruginosa, S. aureus	S. aureus and P. aeruginosa infected-wound model in rats: The membranes significantly reduced the bacterial load in the wounds compared to the control group with a rapid initial eradication.	[196]
	Dressing: Chitosan 190–310 kDa DDA: 75–85% Silver NPs	P. aeruginosa	P. aeruginosa-infected wound model in mice: The mice treated with the polyelectrolyte complex had a reduced bacterial load in the tissue after 14 days of treatment and higher survival than mice treated with gauze.	[197]
	Nanofibers: Chitosan ≈250 kDa DDA: n.a. Indocyanine green	MRSA	MRSA-infected wound model in rats: The indocyanine green-loaded chitosan/PVA nanofibers and illumination demonstrated improved wound healing and reduced bacterial burden in the wound bed compared to all other treatment groups.	[198]
	Dressing loaded with microspheres: Chitosan MMW DDA: ≥85% Gentamycin sulfate	S. aureus E. coli	S. aureus and E. coli-infected wound model in rats: The group treated with gelatin microspheres loaded with gentamycin and platelet-rich plasma on chitosan dressing displayed reduced bacterial load and a faster wound healing rate than the group treated with gauze.	[199]
	Dressing: Chitosan MMW DDA: 97% Graphene oxide Copper NPs	S. aureus	S. aureus-infected wound model in mice: The group treated with the graphene oxide–copper composite in chitosan/hyaluronic acid hydrogel improved wound healing compared with all other groups.	[200]
	Sponge: Chitosan 10–30 kDa DDA: ≥95% Silver NPs	S. aureus	S. aureus-infected wound model in rabbits: the group treated with the silver NP-sponge healed faster than the control group, and although not statistically significant, faster than the marketed silver dressing.	[201]
	Sponge: Chitosan MW: 500 kDa DDA: 90% Quaternary ammonium CNPs	S. aureus	S. aureus-infected wound model in mice: the chitosan sponges loaded with quaternary ammonium CNPs exhibited superior antimicrobial activity compared to sponges without CNPs and untreated mice on days 7 and 10.	[202]

n.a.: not applicable/not denoted; CNP: chitosan nanoparticles, DDA: degree of deacetylation, LMW: low molecular weight, MMW: medium molecular weight, MRSA: methicillin-resistant S. aureus, MW: molecular weight, PVA: poly(vinyl alcohol).