Gingival recession treatment with concentrated growth factor membrane: a comparative clinical trial

Abstract Objective This clinical trial sought to evaluate the clinical effectiveness of concentrated growth factor (CGF) and compare it with connective tissue graft (CTG) with coronally advanced flap (CAF) in the treatment of Miller Class I gingival recessions (GR). Methodology This split-mouth study included 74 Miller Class I isolated (24 teeth) or multiple (50 teeth) GRs in 23 jaws of 19 patients. GRs were randomly treated using CGF (test group: 37 teeth; 12 teeth in isolated GRs, 25 teeth in multiple GRs) or CTG with CAF (control group: 37 teeth;12 teeth isolated GRs, 25 teeth in multiple GRs). Clinical variables, plaque index (PI), gingival index (GI), probing depth (PD), recession depth (RD), recession width (RW), clinical attachment level (CAL), keratinized tissue thickness (KTT), keratinized tissue width (KTW), and root coverage (RC) were assessed at the baseline as well as at three and six months post-surgery. Healing index (HI) were obtained in the second and third weeks post-surgery. Postoperative pain was assessed for the first seven days using a horizontal visual analog scale (VAS). Results No significant change was observed in PI, GI, or PD values in either the intergroup or the intragroup comparisons. A statistically significant decrease was observed in CAL, RD, and RW, and KTT increased in all groups at three and six months compared with the baseline. The control group had greater increases in KTW, KTT, and RC at three and six months. No significant difference was found in CAL or RD at the third and sixth months between the two groups. Healing was found to be similar for both groups in the second and third weeks post-surgery. The VAS values in the control group were higher than in the test group, especially at the second, fourth, fifth, and seventh days postoperatively. Conclusions CTG is superior to CGF with CAF for increasing KTT, KTW, and RC. CGF may be preferable due to decreased postoperative pain.

Therefore, alternative methods are used to treat GRs. 3,4 Platelet concentrates (PCs) are used in the field of periodontology to provide key cells and growth factors to advance healing and promote regeneration. 5,6 Platelet-rich fibrin (PRF) has shown to exhibit slow dissolution and a long-lasting fibrin network structure.
This structure provides a matrix that contains high amounts of growth factors, thrombocytes, and leukocytes. 7 Concentrated growth factor (CGF) is identified as a new approach to produce PRF or a nextgeneration PC. 8,9 When producing CGF, the rotational speed of the centrifuge machine varies between 2400 and 3000 rpm. 8 The variability of the rotation speed during centrifugation results in a fibrin matrix that is larger, more intensive, and includes more growth factors than PRF. [8][9][10][11] Some studies have reported that CGF induces osteogenic differentiation in periodontal ligament stem cells 9 and new bone formation for sinus augmentation, 10 results in a defect fill that was found to be similar to collagen membranes in the surgical treatment of peri-implantitis, 12 and has chemical and mechanical properties similar to those of advanced PRF (A-PRF). 13 In the literature, only one clinical study has examined the treatment of multiple GRs with CGF.
That study showed CGF with CAF surgery increased the keratinized tissue width (KTW) and keratinized tissue thickness (KTT) and may prevent postoperative relapse after the CAF procedure. 14  Plaque index (PI) and gingival index (GI) were recorded regarding the mean mesial, distal, and mid-facial surface measurement of a tooth. 16 A periodontal probe was used at the mid-facial surface to obtain PD, CAL, RD, and KTW measurements; these measurements were rounded to the nearest millimeter.

CGF preparation
Immediately before the surgery test site, intravenous blood was drawn into two tubes without anticoagulant (Vacuette tubes, Greiner Bio-One North America Inc., USA). The blood was then centrifuged with a special centrifuge machine (Medifuge, Silfradent S.r.l., Sofia, Italy). 8 The CGF was removed from the tube and separated from the red blood cell layer with a scissor; a special compressor was then used to obtain a CGF membrane of about 1 mm in thickness, as shown in Figure 1. Two CGF membranes were immediately placed into the recession area above the CEJ, in opposite directions.

Surgical procedures
All surgical procedures were performed in two either CTG or CGF was placed over the exposed root surface and fixed using suspension and simple, resorbable 5.0 sutures (Pegelak, Doğsan, İstanbul, Turkey). The flap was advanced 1 mm coronally from the CEJ to completely cover the CGF or CTG and was sutured with non-resorbable monofilament 5.0 sutures (Polyamid sutures, Seralon, Seragwiessner KG, Naila, Germany). This protocol was applied to both the test and the control groups, as shown in Figures 2 and 3.     Table 1). The CAL median values significantly decreased in both study groups at the third and sixth months when compared with the baseline (p<0.05; Table 1), and the control group had higher baseline CAL median values than the test group.
The CAL values did not differ significantly between the groups (p>0.05; Table 1).
Regarding KTW and KTT, significant increases in the CTG group were observed between the baseline and other follow-up times (p<0.05; Table 1). The changes in the CGF group were statistically significant only for KTT; no significant difference was found for KTW. In the intergroup comparisons, statistically significant differences were observed at the third and sixth months in favor of the control group (p<0.05; Table 2).
The median RD and RW values decreased significantly between the baseline and other followup periods for both groups (p<0.05; Table 1), but  Table 2). The CTG group had higher median RC values than the CGF group for all follow-up periods (p<0.05; Table 2). The increase  in RC in the sixth month when compared with the third month was significant only in the control group (p<0.05; Table 2).

The median HI values significantly increased
in both groups in the third week when compared with the second week (p<0.05; Table 3). In the intergroup comparisons, the median HI values were similar between the groups; without differences (p<0.05; Table 3). In the intragroup comparisons, the increase in the VAS median values seen in the following days was statistically significant in both groups when compared with the baseline (p<0.05; Table 3). The VAS median values of days 2, 4, 5, and 7 were significantly higher after CTG than after CGF (p<0.01; Table 3   the CAF (modified) with CGF group after six months.
Doğan, et al. 14 (2015) reported that CGF treatment did not show any additive effect on the RC results of the CAF procedure. The authors 14 suggested CGF application with CAF might increase the long-term stability of RC due to increasing KTW (0.58 mm) and KTT (0.32 mm), which caused a better attachment gain. Increases of 0.14 mm/0.28 mm, respectively, were observed in the KTW/KTT at the sixth month for the CGF group. Some results of this study showed increased KTT and attachment gains, which agrees with Doğan, et al. 14 (2015). However, CGF had no effect on KTW and showed a lower RC percentage. The    37,38 In this study, the CTG was standardized to be 1.5-2 mm thick, and the graft horizontal and vertical dimensions were adjusted to exceed 2 mm of the exposed root surface.
Despite the attempt to establish a similar recipient bed environment, differences in recipient bed width and graft sizes for isolated and multiple GRs may be considered limitations for RC, healing, and pain assessments.
This study had a split-mouth design with both single and multiple defects. Split-mouth design was more objective than parallel design for clinical studies.