Table 2. Matrix metalloproteinases (MMPs) inhibitors and strategies to improve the stability of the dentin/resin bonding.

Mechanism of action	MMP inhibitor	Method of use	Period of testing	Type of study	References
Chelation	CHX	2% diacetate CHX added into experimental adhesive	1 yr	In vitro	da Silva et al. [58]
		2% digluconate CHX, dentin pretreatment, 60 sec	6 mon	In vitro	Lenzi et al. [59]
		0.01%, 0.05%, 0.1%, 0.2% diacetate CHX added into commercial adhesive	1 yr	In vitro	Stanislawczuk et al. [62]
		0.5%, 1.0%, 0.2%, 0.4% diacetate CHX into experimental adhesive	18 mon	In vitro	de Menezes et al. [43]
		2% digluconate CHX, dentin pretreatment, 60 sec	20 mon	Clinical trial	Ricci et al. [64]
		2% digluconate CHX, dentin pretreatment, 30 sec	1 yr	Clinical trial, in vitro	Brackett et al. [48]
		2% digluconate CHX, dentin pretreatment, 60 sec	4 yr	Clinical trial	Valério et al. [65]
		1% digluconate CHX added into commercial self-etch adhesive primer	2 yr	Clinical trial	Araújo et al. [67]
		2% digluconate CHX, dentin pretreatment, 30 sec	3 yr	Clinical trial	Sartori et al. [68]
		2% digluconate CHX, dentin pretreatment, 60 sec	1 yr	Clinical trial	Galafassi et al. [66]
		2% digluconate CHX, dentin pretreatment, 20 sec	1 yr	In vitro	Daood et al. [74]
		2% digluconate CHX, dentin pretreatment, 60 sec	1 yr	In vitro	Tekçe et al. [94]
	EDTA	EDTA 0.5 M, dentin pretreatment, 60 sec	1 yr	In vitro	Tekçe et al. [94]
	Tetracyclines	2% minocycline, dentin pretreatment, 60 sec	6 mon	In vitro	Singh et al. [86]
	Zinc	ZnO or ZnCl2 added into experimental adhesive and primer	24 hr	In vitro	Osorio et al. [56]
	Galardin	0.2 mM galardin, dentin pretreatment, 30 sec	1 yr	In vitro	Breschi et al. [52]
		5 µM galardin added into experimental adhesive	1 yr	In vitro	da Silva et al. [58]
	Batmastati	5 µM batmastati added into experimental adhesive	1 yr	In vitro	da Silva et al. [58]
	QAS	2%, 5%, 10% QAS, dentin pretreatment, 2 min	14 day	In vitro	Daood et al. [74]
	Quaternary ammonium methacrylates	5% MDPB, 30% METMAC, MCMS, MAPTAC, DDAC, ATA, dentin pretreatment	1 mon	In vitro	Tezvergil-Mutluay et al. [71]
	BAC	BAC-containing acid etchant, 15 sec	1 yr	In vitro	Comba et al. [42]
		0.5% BAC and 1% methacrylate BAC, 30 min	6 mon	In vitro	El Gezawi et al. [40]
		1% BAC-containing acid etchant, 15 sec	6 mon	In vitro	Sabatini et al. [72]
		0.5%, 1% BAC-containing acid etchant, 15 sec
		0.5%, 1% BAC-adhesive
		1% BAC, dentin pretreatment, 15 sec	1 yr	In vitro	Tekçe et al. [94]
	Alcohols	Methanol, Ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, 2-hydroxyethylmethacrylate, 1-pentanol, hexanols, heptanols, octanols, 1,2-ethanediol, 1,3-propanediol.	1 mon	In vitro	Tezvergil-Mutluay et al. [75]
		A series of ethanol concentrations (50, 70, 80, 95, 100%), 15 sec each after acid-etching	24 hr	In vivo	Kuhn et al. [76]
				In vitro
Collagen cross-linking	PA	0.02%, 0.1%, 0.5% PA, dentin pretreatment	12 hr	In vitro	Hiraishi et al. [53]
		3.75% PA, dentin pretreatment, 10 sec, 1 min, 30 min, 60 min, 120 min, 360 min, 720 min	6 mon	In vitro	Epasinghe et al. [80]
		2% PA-containing acid etchant, 15 sec	6 mon	In vitro	Hass et al. [38]
	GA	0.1% GA, dentin pretreatment, 60 sec	24 hr	In vitro	Chiang et al. [79]
		5% GA, dentin pretreatment, 60 sec	24 hr	In vitro	Cilli et al. [78]
		5% GA, dentin pretreatment, 60 sec	6 mon	In vitro	Li et al. [55]
		0.02%, 0.1%, 0.5% GA, dentin pretreatment, 60 sec	12 hr	In vitro	Hiraishi et al. [53]
	RB	0.1% RB - 1 min - UV, 0.1% RB - 2 min - UV, 1.0% RB - 1 min - UV, dentin pretreatment, 60 sec	24 hr	In vitro	Chiang et al. [79]
		0.1%, 1% RB - 5 min - UV or light blue, dentin pretreatment, 60 sec	4 mon	In vitro	Fawzy et al. [54]
	Resveratrol	100, 250, 500, 1,000 µg/mL resveratrol solution, dentin pretreatment, 60 sec	4 mon	In vitro	Porto et al. [46]
	Quercetin	5% quercetin added into adhesive	6 mon	In vitro	Gotti et al. [89]
		100, 250, 500, 1,000 µg/mL quercetin solution, dentin pretreatment, 60 sec	4 mon	In vitro	Porto et al. [46]
Competitive inhibition for active sites of the collagen molecule	Zn	2% ZnCl2 or 10% ZnO added into commercial etch and rinse adhesive, 2% ZnCl2 added into commercial self-etch primer adhesive, 2% ZnCl2 or 10% ZnO added into commercial self-etch bond adhesive	24 hr	In vitro	Osorio et al. [56]
Multiple action mechanisms (by inactivating the active sites and improving the resistance of cross-linked collagen matrices)	Carbodiimides	0.01, 0.02, 0.05, 0.1, 0.3 M carbodiimide, dentin pretreatment, 60 sec	1 mon	In vitro	Tezvergil-Mutluay et al. [34]
		1 M carbodiimide solution, dentin pretreatment, 60 sec	6 mon	In vitro	Singh et al. [86]
	EGCG, green tea	0.1% EGCG solution, dentin pretreatment, 60 sec	6 mon	In vitro	Singh et al. [86]
		1.1% EGCG solution, dentin pretreatment, 60 sec	6 mon	In vitro	Monteiro et al. [90]
		0.1% EGCG solution, dentin pretreatment, 60 sec	1 yr	In vitro	Neri et al. [39]

CHX, chlorhexidine; EDTA, ethylenediaminetetraacetic acid; QAS, quaternary ammonium silane; METMAC, [2(methacryloyloxy)ethyl] trimethylammonium chloride; MCMS, methacryloyl choline methyl sulfate; MAPTAC, [3(methacryloylamino)propyl] trimethylammonium chlorid; DDAC, diallyldimethylammonium chloride; ATA, 2-acryloxyethyltrimethylammonium chloride; MDPB, 12-methacryloyloxydodecylpyridinium bromide; BAC, benzalkonium chloride; PA, proanthocyanidin; GA, glutaraldehyde; RB, riboflavin; Zn, zinc; EGCG, epigallocatechin-3-gallate.