Table 2. Characteristics of the included studies.

	Hasturk et al. (2006) [30]	Hasturk et al. (2007) [29]	Hasturk et al. (2015) [28]	Lee et al. (2016) [31]	Mizraji et al. (2018) [32]
Experimental animals	New Zealand white rabbits	New Zealand white rabbits	New Zealand white rabbits	Wistar rats	BALB/c or B6 mice
Experimental periodontitis	Ligature and P. gingivalis	Ligature and P. gingivalis	Ligature and P. gingivalis	Ligature	P. gingivalis
Resolvins/ placebo/control evaluated	RvE1 /ethanol/ systemic metronidazole	RvE1 /ethanol	RvE1/ethanol	RvE1/vehicle (not specified)	RvD2/ 2% carboxymethylcellulose (CMC) solution
Subject distribution	Experimental (n=6); Placebo (n=6); Systemic metronidazole (n=3); Ligature alone (n=3); No treatment (n=3)	Disease (n=5); Ethanol (n=10); RvE1 treatment (n=14)	No treatment (n=5); 4 μg RvE1‐treated (n=5); 0.4 μg RvE1‐treated; (n=5) Ethanol‐treated (n=5)	Prevention: No ligature (n=4); Ligature only (n=4); Ligature + RvE1 (n=4); Ligature + vehicle (n=4); Treatment : No ligature (n=6); Ligature only (n=6); Ligature + vehicle (n=3); Ligature+RvE1 (n=3)	Control; P. gingivalis +RvD2; P. gingivalis
Study duration	12 weeks	12 weeks	12 weeks	Prevention: 4 weeks; Treatment: 6 weeks	8 weeks
Resolvins application and concentration	Topical, 4 μg per tooth in ethanol on alternate days for six weeks	Topical, 4 μg per tooth in ethanol on alternate days for six weeks	Topical, 4 μg in 5% ethanol in saline/site or 0.4 μg in 5% ethanol in saline/site on alternate days for six weeks	Topical, 0.1 μg/μl on alternate days for four weeks in prevention group 4 ml of a 0.25 mg/ml solution on alternate days for six weeks in the treatment group	Intraperitoneally, Three doses of 0.5 μg RvD2 in 150 μl of the sterile saline solution followed by six doses of 0.1 μg of RvD2 over the next two weeks
Periodontal parameters evaluated	Alveolar bone loss	Alveolar bone loss + pocket depth + infrabony pocket depth + tooth mobility	Alveolar bone loss + pocket depth + infrabony pocket depth + tooth mobility	Alveolar bone loss	Alveolar bone loss
Outcome	Compared to other groups, topical RvE1 therapy at the ligature site reduced periodontal tissue and bone damage by >95%.	RvE1 treatment showed a statistically significant decrease in pocket depth and infrabony defect depth compared to baseline periodontitis and all other treatment groups (p 0.05). In contrast, those treated with vehicle alone resulted in 13% bone loss.	RvE1 (0.4 g/site) applied orally and topically showed a dose/response reduction of periodontal deterioration. RvE1-treated samples (4 g/site) showed good histological architecture and intact bone.	Prevention: When compared to control, RvE1 at low (0.1 g/l) and high (0.5 g/l) doses reduced alveolar bone loss by 1.51 and 1.73 mm2 (30%–40%), respectively. Treatment: The bone loss was reduced by 30–40% in the RvE1 group compared to the control.	The P. gingivalis-infected group had significantly lower residual bone volume compared to the other groups.
Conclusion	In rabbits with periodontitis, topical treatment of RvE1 provided significant protection against inflammation-induced tissue and bone loss.	RvE1 modifies the inflammatory response, causing it to resolve more quickly and effectively prevent the chronic phase. Tissue regeneration is aided by the removal of inflammation in the healing lesion.	RvE1, when applied as a topical nanotherapeutic drug, reduced atherosclerotic alterations and periodontal bone loss caused by periodontitis in an animal model of periodontitis and atherogenesis.	In the rat ligature-induced periodontitis paradigm, prophylactic RvE1 therapy dramatically reduces alveolar bone loss.	RvD2 therapy inhibits destructive inflammation and alveolar bone loss in mice with experimental periodontitis.