Clinical evaluation of GEM 21S(®) and a collagen membrane with a coronally advanced flap as a root coverage procedure in the treatment of gingival recession defects: A comparative study.

AIM: Clinical evaluation of efficacy of rhPDGF-BB plus beta tricalcium phosphate (GEM 21S(®)) along with a collagen membrane in root coverage using a coronally advanced flap.
MATERIALS AND METHODS: This human case series evaluated the clinical outcome of rhPDGF-BB with beta-tricalcium phosphate (GEM 21S®) and a collagen membrane in the treatment of recession defects using a coronally advanced flap. Patients were followed postoperatively, and healing was evaluated at 1, 3, and 6 months, with recession depth as the primary outcome measure.
RESULTS: This pioneer case series revealed a favorable tissue response to GEM 21S® and collagen membrane from both clinical and esthetic point of view in regenerative periodontal surgery.

INTRODUCTION

The increasing interest in esthetics and the subsequent need to solve related problems such as hypersensitivity and root caries have favored the development of many surgical procedures that permit the coverage of exposed roots. Obtaining predictable and esthetic root coverage has become an important part of periodontal therapy. However, at times the reason for desiring the root coverage procedure may be simply to improve the esthetics of an area. Certainly, this increase in demand for root coverage procedures will fuel a need to develop new procedures involving latest periodontal regenerative techniques. Periodontal regeneration has become one of the primary objectives of periodontal therapy including root coverage procedures. The resulting scientific endeavors have elucidated modes of periodontal wound healing, the growth of periodontal cells and their association with the surrounding matrix, and growth-promoting factors. Growth factors such as platelet-derived growth factor (PDGF) and transforming growth factor (TGF), contained in the granules of blood platelets and released at sites of injury, have been shown to be important in the normal healing of bone, gingiva, and skin.[1]

The future of the periodontal regeneration may depend on the merging of various technologies and biological concepts, including the possible use of biological barriers, various bone and periodontal growth inducers, and artificial matrices that will attract or carry the cells necessary for regeneration.

The desire to increase the predictability of successful outcomes when using osteoconductive matrices has led to the development of regenerative treatments designed to stimulate the cells responsible for regeneration. The use of cell-stimulating proteins in combination with osteoconductive scaffolds and cells in periodontics is based on the principles of tissue engineering.[2] This approach combines three key elements to enhance regeneration: Conductive scaffolds, signaling molecules, and cells.

Thus, the ideal periodontal treatment should include recruitment of embryonic, pluripotential cells (i.e. periodontal progenitor cells) capable of differentiating into specialized cell types, which will form a functional syncytium connected by highly specialized and appropriately oriented collagen fibers.

A new and superior wound healing and bone regeneration technology termed growth-factor-enhanced matrix (GEM 21S®) has recently become available for clinical use. This graft material consists of a concentrated solution of pure recombinant human platelet-derived growth factor (rhPDGF-BB), the synthetic form of the body's key natural wound-healing stimulator PDGF-BB, and an osteoconductive (bone scaffold) matrix which is beta-tricalcium phosphate (β-TCP). This is the first available purified, recombinant (synthetic) growth factor product and is the result of over a decade of extensive research. Clinical and animal study results with this graft material demonstrate that it is capable of simultaneously promoting wound healing, regeneration of bone, and acceleration of gingival attachment gain in challenging periodontal and peri-implant defects.

This study was carried out to evaluate and compare the clinical efficacy of GEM 21S® (rhPDGF-BB and beta-tricalcium phosphate) along with a collagen membrane (Healiguide) to the use of only a collagen membrane for the treatment of recession defects using a coronally advanced flap in both the cases based on various clinical parameters.

AIMS AND OBJECTIVES

Clinical evaluation of efficacy of rhPDGF-BB plus beta-tricalcium phosphate (GEM 21S®) along with a collagen membrane in root coverage using a coronally advanced flap

Comparison of GEM 21S® plus collagen membrane versus collagen membrane alone in root coverage using a coronally advanced flap, on various clinical parameters.

MATERIALS AND METHODS

The subjects for the present study were selected from the Out Patient Department, Department of Periodontology and Oral Implantology, MM College of Dental Sciences and Research, Mullana, Distt. Ambala (Haryana). The subjects were clearly explained the study protocol and procedure and a duly signed written consent was taken from them.

A total of 14 sites from seven subjects were selected and divided into two groups – Group A and Group B according to treatment modalities by using the split-mouth design technique.

Group A: Seven sites were treated with GEM 21S® (rhPDGF-BB plus beta-tricalcium phosphate) and collagen membrane (Healiguide™) with a coronally advanced flap.

Group B: Seven sites were treated with a coronally advanced flap with only a collagen membrane (Healiguide™).

The clinical parameters assessed were:

Vertical gingival recession depth (from the most apical point of the acrylic stent to the most apical point of the facial gingival margin)

Clinical attachment level (from the most apical part of stent to the base of pocket)

Clinical probing depth

Width of keratinized tissue

Surgical procedure

(Group A)

After evaluation of pre-clinical records and obtaining adequate local anesthesia, two horizontal beveled incisions were given, mesial and distal, to the recession defect located at a distance from the tip of the anatomical papillae equal to the depth of the recession plus 1 mm. This was followed by two beveled oblique, slightly divergent, incisions starting at the end of the two horizontal incisions and extending to the alveolar mucosa. Surgical procedure as shown from Figures 1 to 13

Figure 1

Group A: Measuring recession with acrylic stent and UNC probe

Figure 13

Postoperative at 6 months (full root coverage)

The resulting trapezoidal-shaped flap was elevated with a split–full-split approach in the coronal-apical direction: The surgical papillae comprised between the horizontal incisions and the probable sulcular area apical to the root exposure were elevated split thickness keeping the blade almost parallel to the root, and the soft tissue apical to the root exposure was elevated full thickness inserting a small periosteal elevator into the probable sulcus and proceeding in the apical direction up to exposing 3 - 4 mm of bone apical to the bone dehiscence

The releasing vertical incisions were elevated split thickness keeping the blade parallel to the bone plane, thus leaving the periosteum to protect the underlying bone in the lateral areas of the flap. Apical to bone exposure flap elevation continued split thickness and finished when it was possible to move the flap passively in the coronal direction.

In order to permit the coronal advancement of the flap, all muscle insertions present in the thickness of the flap were eliminated. Coronal mobilization of the flap was considered ‘adequate’ when the marginal portion of the flap was able to passively reach a level coronal to the CEJ of the tooth with the recession defect.

The facial soft tissue of the anatomic inter-dental papillae coronal to the horizontal incisions was de-epithelialized to create connective tissue beds to which the surgical papillae of the coronally advanced flap were sutured. The exposed root surface, after thorough root planing , was conditioned with ethylenediamine-tetraacetic acid (EDTA 24%) for 2 min to remove the smear layer and thoroughly rinsed with sterile saline.

Any remaining PDL tissue coronal to the alveolar bone was preserved. The rhPDGF-BB solution was then applied to the exposed root surface and to the coronal ligament fibers. A small amount of β-TCP was saturated with the rhPDGF-BB solution and placed below the CEJ, over the denuded root surface and extending approximately 2 - 3 mm onto the adjacent bone.

The collagen membrane was also saturated with the PDGF solution prior to membrane placement. Once saturated, the membrane was placed over the beta-TCP according to standard GTR surgical procedure and sutured bilaterally to the de-epithelialized papilla region.

Subsequently, the membrane was covered with the coronally advanced flap. The tissue flap was then secured at the level of the CEJ by suturing the flap to the de-epithelialized papilla regions with 5-0 gut sutures. The vertical incisions were closed with 5-0 gut sutures. Any remaining rhPDGF-BB solution was dispensed onto the coronally advanced flap, followed by the placement of tin foil and periodontal dressing.

Requisite post-operative instructions and medications were advised to the patient. The patients were given amoxicillin and cloxacillin combination for antibiotic coverage and a combination of diclofenac sodium and paracetamol as an anti-inflammatory drug. Chlorohexidine mouthwash was also prescribed twice daily for 2 weeks to every patient.

Horizontal incision

Vertical incision

Cervicular incision

Flap elevation

Application of 24% EDTA to the root surface

Application of the rhPDGF solution

Beta-TCP soaked in the rhPDGF solution

Application of beta-TCP and rhPDGF mixture

Placement of collagen membrane

Suturing of collagen membrane

Coronal advancement of flap and sutured

Group B

A procedure identical to that used in sites of Group-A subjects

However, instead of PDGF and beta TCP (GEM21S®), sites of Group-B subjects received a collagen membrane (Healiguide) only over the denuded root surface followed by a coronally advanced flap.

Patients were called after 24 h for check up to evaluate any discomfort, swelling, pain, any bleeding, or displacement of periodontal pack. One week following surgery, the periodontal pack was removed and area irrigated with saline, and a repeat periodontal pack was placed in the case of uneventful healing.

Patients were recalled every 2 weeks following surgery for 1 month and subsequently every month for the next 6 months for examination of the treated surgical site. Clinical measurements recorded pre-operatively were repeated at 1, 3, and 6 months, postoperatively, and subjected to statistical analysis.

RESULTS AND DISCUSSION

Gingival recession depth

Group A

In this study, there was a statistically significant (P<0.05) reduction in the mean difference of gingival recession depth scores from baseline to 1, 3, and 6 months with the P value of 0.016, 0.016, and 0.016, respectively. The percentage gain in root coverage from baseline to 1 month was 57.14%, increased to 70.24% at 3 months and remained the same (70.24%) at 6 months. These results are in accordance with the clinical pilot study done by McGuire et al.[3] who compared GEM 21S® to the subepithelial connective tissue graft in root coverage [Table 1 and Figure 14].

Table 1

Mean differences in gingival recession, clinical attachment level and width of keratinised tissue between different intervals of group A and B

Figure 14

Percentage gain in root coverage, clinical attachment level and width of keratinized tissue of Group A and B at different intervals

Various studies using rh-PDGF-BB and β-TCP in periodontal defects such as done by Nevins[4] also report gain in root coverage. Nevins et al.[5] to their knowledge did the largest, prospective, randomized, triple-blinded clinical trial to date assessing a putative regenerative and wound-healing therapy using rhPDGF-BB and B-TCP and giving similar results such as reduced gingival recession.

Studies done by Nevins,[6] Camelo et al.,[7] and Nevins and Lynch[8] used rhPDGF-BB and allograft (demineralized freeze-dried bone allograft) in various periodontal defects has reported root coverage.

In this study, there was a statistically significant (P<0.05) decrease in the mean difference of gingival recession depth scores from baseline to 1, 3, and 6 months with the P value of 0.016, 0.024, and 0.024, respectively. The percentage gain in root coverage from baseline to 1 month was 45.95%, decreased to 34.76% at 3 months, and remained the same (34.76%) at 6 months. The results are in accordance with the study done by Kimble et al.[9] who reported 68.4% root coverage at 6 months using only collagen. These results also harmonize with bioabsorbable barrier studies as done by Muller et al.[10] Prato et al.,[11] Shieh et al.,[12] Borghetti et al.,[13] Harris and Romagna-Genon,[14] Tinti et al., Rachlin et al.,[1415] Trombelli et al.,[16] and Amarante et al.[17] which showed root coverage ranging from 55% to 75% [Table 1 and Figure 14].

Comparison between Group A and B

On comparison of Group A versus Group B, there was a statistically non-significant (P>0.05) decrease in the mean difference of gingival recession depth scores from baseline, 1, 3, and at 6 months with the P value of 0.362, 0.352, 0.056 and 0.056, respectively [Table 2 and Figure 14].

Table 2

Mean differences in gingival recession, clinical attachment level, probing depth and width of keratinised tissue between group A and B at different intervals

Clinical attachment level

In this study, there was a statistically significant (P<0.05) increase in the mean difference of clinical attachment level scores from baseline to 3 and 6 months for P value 0.016 and 0.017, respectively. The percentage gain in clinical attachment levels at 3 months was 52.86% and increased to 58.10% at 6 months [Table 1 and Figure 14].

In this study, there was a statistically significant (P<0.05) increase in the mean difference of clinical attachment level scores from baseline to 3 and 6 months with the P value of 0.015 and 0.026, respectively. The percentage gain in clinical attachment levels at 3 months was 31.97% and decreased to 29.59% at 6 months. The results are in accordance with the study done by Kimble et al.,[9] Christine,[17] and Wang et al.[18] who also reported gain in clinical attachment levels from baseline to 6 months [Table 1 and Figure 14].

On comparison, there was a statistically non-significant (P>0.05) difference in clinical attachment level scores between the groups at baseline and 3 months with the P value of 0.833 and 0.075, respectively, but at 6 months, there was a statistically significant (P<0.05) difference with the P value of 0.049 which showed higher gain in the clinical attachment level of Group A [Table 3 and Figure 14].

Table 3

Mean differences in probing depth between different intervals of group A and B

Probing depth

In this study, there was a statistically significant (P<0.05) reduction in the mean difference of probing depth scores from baseline to 3 and 6 months with the P value of 0.025 and 0.020, respectively. The percentage reduction in probing depth at 3 months was 30.95% and increased to 42.86% at 6 months [Table 2 and Figure 15].

Figure 15

Percentage reduction in probing depth of Group A and B at different intervals

In this study, there was a statistically significant (P<0.05) reduction in the mean difference of probing depth scores from baseline to 3 month, P value 0.046, and a statistically non-significant (P>0.05) decrease from baseline to 6 months with the P value of 0.083. The percentage reduction in probing depth at 3 months was 28.57% and decreased to 21.43% at 6 months.

On comparison of Group A versus Group B, there was a statistically non-significant (P>0.05) difference of probing depth scores at baseline, 3, and 6 months for P value of 0.141, 0.606, and 0.298, respectively. However, there was more reduction in probing depth observed for the Group A sites [Table 3 and Figure 15].

Width of keratinized tissue

In this study, there was a statistically significant (P<0.05) decrease in the mean difference of the width of keratinized scores from baseline to 1, 3, and 6 months with the P value of 0.016, 0.016, and 0.016, respectively, which is suggestive of the increase in the width of keratinized tissue at the site. The percentage gain in the width of keratinized tissue at 1 month was 46.19%, which increased to 58.10% at 3 months, and remained the same (58.10%) at 6 months [Table 1 and Figure 14].

In this study, there was a statistically significant (P<0.05) decrease in the mean difference of width of keratinized scores from baseline to 1, 3, and 6 months with the P value of 0.016, 0.024, and 0.024 , respectively which is suggestive of the increase in width of the keratinized tissue at the site. The percentage gain in the width of keratinized tissue at 1 month was 45.48% , decreased to 35.00% at 3 months, and remained the same (35.00%) at 6 months [Table 1 and Figure 14].

On comparison, there was a statistically non-significant (P>0.05) increase in the mean difference of the width of keratinized tissue scores from baseline, 1, 3, and 6 months with the P value of 1.000, 0.731, 0.061, and 0.061, respectively [Table 3 and Figure 14].

CONCLUSION

On observing the clinical parameters, the present study showed better results in both the groups of GEM 21S® and collagen (Healiguide) and only collagen-treated sites with a statistically significant difference in clinical parameters at various intervals. On comparison, there was no statistically significant difference observed, these suggestive of the fact that both GEM 21S® along with collagen and only collagen (Healiguide) can be used effectively in root coverage procedures. However, Group A sites showed better results in root coverage than Group B sites.

Limitations and future directions

This study was a short-term clinical study with a small sample size and no histological evaluation. Studies should be designed with large sample sizes and histological evaluation to further compare the predictability of the above said procedures and also in other periodontal defects requiring regenerative therapy.