Identification of Gingival Crevicular Fluid Sampling, Analytical Methods, and Oral Biomarkers for the Diagnosis and Monitoring of Periodontal Diseases: A Systematic Review

Table 2

Summary of microcapillary techniques used in GCF collection.

Reference	Analysis	Markers	Aim	Main findings
[12]	ELISA	IL-1β	To find the difference in the IL-1β levels between healthy control and CP patients.; To find the relationship between clinical parameters and IL-1β levels.	The levels of IL-1β increased in accordance with progression of periodontal disease.
[13]	ELISA	Resistin	To measure and compare the levels of resistin in GCF in healthy subjects, chronic periodontitis, and diabetes mellitus type 2 (T2DM) patients.	The level of resistin increased in CP and T2DM patients. Hereafter, the level of resistin in GCF could be considered as a biomarker for periodontitis in T2DM patients.
[14]	ELISA	TNF-α	To measure TNF-α levels in GCF and in serum, and to find the effect of periodontal disease on TNF-α levels.	TNF-α level in GCF could be used as a biomarker for periodontal disease.
[15]	ELISA	Monocyte chemoattractant protein (MCP-1)	To determine MCP-1 levels in GCF, serum, and saliva, and to evaluate the effect of periodontal therapy on MCP-1 levels.	GCF and saliva MCP-1 levels could be used as biomarkers to indicate the severity of periodontal disease.
[16]	ELISA	Prostaglandin E2 (PGE2)	To evaluate PGE2 levels in GCF in healthy subjects and patients with periodontal disease, before and after treatment.	The levels of PGE2 positively correlated to the severity of periodontal disease.
[17]	SPM	Alkaline phosphatase (ALP)	To compare GCF ALP levels in patients with CP before and after nonsurgical periodontal treatment.	GCF ALP levels could monitor the periodontal disease status and effect of nonsurgical periodontal treatment.
[18]	SPM	ALP	To measure the GCF ALP levels in different periodontal disease stages.	ALP levels increased with periodontal disease progression. Thus it could be considered a good biomarker for periodontal disease progression.
[19]	ELISA	Oncostatin M (OSM)	To determine the level of OSM in GCF of gingivitis and CP patients and to evaluate the effect of periodontal treatment on level of OSM.	Levels of OSM correlated to the clinical periodontal parameters (PD and CAL) and could be used as a biomarker for periodontal disease.
[20]	ELISA	Cortisol	To measure the levels of salivary and GCF cortisol in anxious and nonanxious patients with CP.	Anxiety had a positive effect on periodontal disease and the levels of cortisol in GCF can be considered a biomarker for CP.
[21]	ELISA	Plasma glutathione peroxidase (eGPx)	To determine the eGPx levels in GCF to clarify the effect of oxidants and antioxidants on periodontal disease.	There was a positive correlation between the levels of eGPx in GCF and periodontal diseases. eGPx could be considered as a marker of oxidative stress in periodontal diseases.
[22]	ELISA	MCP-1	To evaluate the MCP-1 role during the development of periodontal disease and to evaluate the outcome of periodontal treatment on the levels of MCP-1.	The levels of MCP-1 elevated in accordance with the severity of periodontal disease. Periodontal treatment reduced the MCP-1 levels in GCF.
[23]	ELISA	MCP-1, IL-18	To examine MCP-1 and IL-18 GCF levels in control and periodontally diseased patients.	IL-18 and MCP-1 levels positively correlated to periodontal disease status.
[24]	ELISA	Pentraxin-3 (PTX3)	To evaluate PTX3 levels in Plasma and GCF in subjects with and without periodontal disease.	PTX3 levels in GCF could be considered as a biomarker for periodontal disease.
[25]	EIA	Neopterin	To determine if neopterin levels in GCF correlated with periodontal clinical parameters.	Neopterin increased proportionally with the severity of periodontal disease and it could be considered as a biomarker of periodontal disease.
[26]	ELISA	C-reactive protein (CRP)	To measure the levels of CRP in different periodontal disease stages.	Levels of GCF CRP and serum CRP elevated proportionately to periodontal disease severity.
[27]	EIA	Leukotriene B4 (LTB4)	To evaluate the relationship between periodontal clinical parameters and GCF LTB4 levels from diseased sites, previous to and after treatment of periodontitis.	GCF LTB4 levels increased with the severity of periodontal disease and reduced after nonsurgical periodontal treatment.
[28]	Sandwich enzyme immunoassay kit	Vascular endothelial growth factor (VEGF)	To find the correlation between GCF VEGF levels and the periodontal clinical parameters.; To find if there was a correlation between the levels of VEGF in GCF and serum.	There was a positive correlation between the levels of VEGF in GCF and the periodontal clinical parameters. The same correlation was observed between the levels of VEGF in GCF and serum.
[29]	ELISA	Visfatin	To determine the concentrations of visfatin in GCF and serum in control and periodontally diseased patients in the presence and absence of T2DM.	Positive associations were observed between the levels of visfatin and periodontal disease in all study groups.
[30]	ELISA	IL-17, IL-18	To discover the role of IL-18, IL-17 in different periodontal disease stages before and after treatment.	IL-18 levels in GCF were found to correlate with periodontal disease severity, and periodontal treatments caused a decline in its concentration. IL-17 was not detected in the GCF.
[31]	ELISA	VEGF	To determine the level of VEGF in different periodontal disease stages and to explore the effect of treatment on VEGF levels in GCF.	Levels of VEGF in GCF elevated in relation to periodontal disease severity. Periodontal therapy led to a decrease in their levels.
[32]	ELISA	Visfatin	To measure the serum and GCF visfatin levels.; To explain the role of scaling and root planning on visfatin levels.	Visfatin levels increased in accordance with disease progression and could be used as biomarkers during the treatment of periodontal disease.
[33]	Enzyme assay	ALP	To determine the existence and ALP levels activity in GCF in different stages of periodontal disease.	There was a relationship between periodontal disease and ALP level.
[34]	ELISA	Cystatin C	To measure the level of cystatin C in serum and GCF in different periodontal disease stages.	Cystatin C levels in serum and GCF correlated to the severity of periodontal disease and reduced after treatment.
[35]	ELISA	Osteopontin (OPN)	To measure the relation between clinical parameters and osteopontin (OPN) levels in GCF.; To evaluate the effect of periodontal treatment on OPN levels.	GCF OPN levels increased with the severity of periodontal disease and the treatment resulted in a decrease in OPN levels.