Table 2.

Summary of the reviewed studies involving antibacterial components in hydrogels for wound healing application.

Biomaterials	Antibacterial component	Concentration	Antibacterial Mechanism	Bacterial strains tested	In vivo	Main Results	Ref
Chitosan & Agarose	Chitosan	125–400 μg/mL	Electrostatic interaction with bacteria membrane	S. aureus	+	Improved re-epithelialization and reduction of inflammation. Hydrogels with CS content higher than 188 μg/mL showed antibacterial activity against S. aureus.	[110]
Chitosan and konjac Glucomannan (KGM)	Chitosan	⁓2.5% w/v	Electrostatic interaction with bacteria membrane	S. aureus E. coli	+	Enhanced wound healing and re-epithelialization Antibacterial rate against S. aureus and E. coli was over 95%.	[105]
Polydextran aldehyde/Polyethylenimine (PDA/PEI)	PEI	6.9% w/v	Electrostatic interaction with bacteria membrane	S. aureus E. coli S. pyogenes	+	Antibacterial activity of hybrid hydrogels was enhanced against S. pyogenes by increasing the concentration of PEI	[106]
ε-poly-l-lysine polyethylene glycol based (PPD) hydrogel	ε-poly-l-lysine (EPL)	5% w/v of PPD conjugate	Surface zeta potentials which damage bacteria membrane	S. aureus E. coli	+	PPD hydrogel promoted antibacterial effect and accelerated rre-epithelialization and wound healing compared to fibrin glue as control group.	[112]
Quaternized chitosan (QCS)/benzaldehyde terminated Pluronic®F127+Curcumin	QCS/Curcumin	2.7% w/v QCS and 1% w/v curcumin	Blocking the assembly dynamics of FtsZ in the Z ring	S. aureus E. coli	+	Excellent wound healing rate, granulation tissue formation, and collagen disposition. Proper antioxidant and antibacterial ability against S. aureus and E. coli.	[116]
Honey-chitosan (CS)	Honey	75%, 50% and 25% w/v of honey.	Low water activity, low pH and generation of peroxide, nitric oxide, and prostaglandin	P. aeruginosa S. aureus K. pneumonie S. pyogenes	+	Among honey-CS hydrogels, the sample with highest honey concentration showed strongest antimicrobial effect against four different bacteria species. Higher wound contraction for the wounds treated with 75% honey - chitosan gel compared to control and commercially available wound dressing.	[119]
Carboxylated agarose/tannic acid (TA) hydrogel	TA	0.5% w/v	Enhanced permeability and disruption of the bacteria membrane, enzyme inhibition	E. coli	+	Improved cell migration and proliferation for cells exposed to hydrogels containing TA Antimicrobial activity against both S. aureus and E. coli.	[121]
(GelMA)/(MeTro) hydrogel + AMP Tet213	AMP Tet213	0.1%, 0.3%, and 3 % w/v	Electrostatic interaction with bacteria membrane	E. coli P. aeruginosa S. aureus	+	Hydrogels containing 0.1 and 0.3% w/v AMP showed antibacterial effects similar to 3% (w/v) Zinc Oxide (ZnO) in the same structure.	[88]
Alginate-Chitosan hydrogel/Tetracycline hydrochloride loaded gelatin microsphere	Tetracycline hydrochloride	1% w/v TH in gelatin microspheres (GM). 30 mg/mL GM.	Protein synthesis inhibition	S. aureus E. coli	–	Sustained release of TH in vitro & strong bacterial growth inhibition effects against S. aureus and E. coli.	[130]
CS/PVP + silver sulfadiazine	CS + silver sulfadiazine	⁓1.4% w/v of Cs	Electrostatic interaction with bacteria membrane/Damaging the cell membrane	E. coli	–	Antibacterial activity was observed for all samples (without and with different concentrations of PVP). T6-PVP-0.5 sample exhibited a release profile of 91.2% in PBS within 80 min.	[131]
Guar gum (GG) Gelatin dopamine conjugate (Gel-DA) Silver nanoparticles (Ag NPs)	Silver nanoparticles (Ag NPs)	0.5, 1, 2 mg/mL	Cell wall and cytoplasmic membrane disruption by silver ions, protein synthesis inhibition by ribosomes denaturation	S. aureus E. coli	+	Inherent antibacterial activity exerted by Ag NPs was enhanced by NIR irradiation. Antibactericidal rates of 96.88% for S. aureus and 98.96% for E. coli.	[240]
Quaternized chitosan (QCS) Ferric iron (Fe) Protocatechualdehyde (PA),	Quaternized chitosan (QCS)	5% w/v	Electrostatic interaction between the polycationic structure and anionic components of microorganisms	S. aureus E. coli MRSA	+	MRSA-infected wounds treated with QCS-PA@Fe showed accelerated wound healing and the inherent bactericidal capacity of QCS was enhanced by NIR irradiation. Healed wounds showed less inflammatory response, more blood vessels and hair follicle formation.	[241]
Chitosan and poly (Vinyl alcohol)	Heparinized ZnO nanoparticles	0%, 0.5%, 1.0%, and 2.0% w/v	Infiltrating into the bacteria membrane and damaging lipids and proteins [162].	S. aureus and E. coli	+	Adding heparin to nanoparticles boosts their antibacterial effect. Promoted wound closure, re-epithelialization, and collagen deposition.	[125]
Sodium alginate and gelatin	Silver nanoparticles	(1.0, 2.0, and 4.0 mM)	Damage to cell membrane and inhibition of DNA replication	S. aureus and P. aeruginosa	+	Hydrogels with MICs of 0.50 g/mL and 53.0 g/mL were found to have significant bactericidal activity against S. aureus and P. aeruginosa, respectively. Improved wound closure and granulation tissue for the wounds treated with nanoparticle-containing hydrogels in vivo.	[126]
Glycidyl methacrylate functionalized quaternized chitosan (QCSG), gelatin methacrylate (GM)	Graphene oxide	0% to 0.5%, 1%, and 2% w/v	Oxidative stress, membrane stress, and electron transfer [242]	S. aureus, E. coli, and MRSA	+	Improved wound closure rate, angiogenesis, and collagen deposition in vivo in S. aureus infected mice full-thickness treated by hydrogels.	[127]
Bacterial cellulose	Multiwalled carbon nanotubes (MWCNT)	0.1% w/v	Damaging bacteria membrane	S. aureus, E. coli, P. aeruginosa, MRSA, S. Typhi, and klebsiella sp	+	Antibacterial activity of the hydrogel against 6 bacteria strains. Faster healing of diabetic wounds in the BC-MWCNT group (99%) vs. negative control (77%) in 21 days. Improved re-epithelialization of the epidermis and healthy granulation tissue.	[128]