Abstract
Background
This case study documents the application of connective tissue graft (CTG) combined with biologics on treating challenging gingival recession cases of mandibular anterior teeth caused by orthodontic tooth movement.
Methods
Three patients presented for periodontal consultation due to gingival recession resulting from orthodontic treatment. The patients reported esthetic concerns and discomfort while brushing their teeth. The gingival defects were mainly localized to the mandibular incisors, with recession depths ranging from 1 to 5 mm and complicated by loss of papilla and a lack of keratinized tissue. RT2 gingival recession with thin gingival phenotype was confirmed. All gingival defects were managed using recombinant human fibroblast growth factor‐2 (rhFGF‐2) treated CTG. The recipient sites were prepared using tunnel or modified tunnel techniques. CTG harvested from the hard palate was treated with rhFGF‐2 for 3 min then inserted into the prepared tunnel space and secured with a sling suture technique for coronal advancement.
Results
The three patients were followed from 6 months to 6 years. Generally, initial wound healing was within normal limits during the first several weeks. The recession defects were successfully covered, achieving a nearly 100% root coverage rate. The combination of CTG+rhFGF‐2 resulted in satisfying recession depth reduction, papilla augmentation, and gain of keratinized tissue. Patients were satisfied with the improvement of esthetics and function.
Conclusions
This innovative approach demonstrates that rhFGF‐2 treated CTG significantly improves the mucogingival problems caused by orthodontic treatment. Successful phenotype modification provides functional and esthetic improvement as well as long‐term stability of periodontal health.
Plain Language Summary
Receding gums are a common complication after wearing dental braces, which sometimes can be severe if the initial gum tissue is thin. This complication could cause tooth sensitivity, discomfort when brushing, and compromised esthetics. To regenerate the lost tissue, a connective tissue graft (CTG) harvested from the roof of the oral cavity is very commonly used as a transplantation option with substantial supporting evidence. However, for cases of severe gum recession, CTGs still have limitations on treatment. Therefore, clinicians and researchers are dedicated to improving treatment outcomes by adding biomaterials to the graft to enhance clinical outcomes. A relatively new material, recombinant human fibroblast growth factor‐2 (rhFGF‐2), has proven to be effective in periodontal regenerative treatments and could potentially augment the soft tissue regenerative capacity of the graft. This case study documents the application of rhFGF‐2 in combination with CTGs for treating severe gum recession in three patients. The treatment results demonstrate significant improvements with follow‐up data ranging from 6 months to 6 years. These improvements include the coverage of exposed root surfaces, regeneration of tissue between teeth, and thickening of gum tissue. Patients were satisfied with the positive changes in function and esthetics resulting from this approach.
Keywords: biological products, cosmetic dentistry, fibroblast growth factors, gingival recession, phenotype
INTRODUCTION
Many etiological factors are associated with the development of gingival recession. Among these factors, orthodontic tooth movement caused a gingival recession in approximately 20%–25% of patients 2–5 years after orthodontic treatment. 1 Regarding treatment, connective tissue graft (CTG) based techniques are reported as the most predictable and effective approach for root coverage. 2 , 3 However, these techniques still have limitations when treating advanced gingival recession defects, such as RT2 or RT3 gingival defects. For these defects, root coverage using CTG alone resulted in a 57.2% mean root coverage rate and 0% complete root coverage 36 months postoperatively. 4 Therefore, some researchers attempted to add biomaterials to CTGs for treating RT2 gingival recession defects and evaluated the effectiveness of the selected combination in clinical studies. 5 , 6 , 7
Biologic agents, such as enamel matrix derivative (EMD), platelet‐rich fibrin (PRF), and recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB), have proven to be effective in periodontal hard and soft tissue regeneration. 8 In 2016, recombinant human fibroblast growth factor‐2 (rhFGF‐2) was approved for clinical usage in Japan and became the first commercially available rhFGF‐2‐based biomaterial in the world. 9 Early clinical trials demonstrated that the administration of 0.3% rhFGF‐2 to 2‐ or 3‐wall vertical bony defects resulted in significant periodontal tissue regeneration. 10 , 11 Animal studies revealed that FGF‐2 promoted effective angiogenesis and mesenchymal cell mitosis within the periodontal ligament. 12 , 13 Moreover, a recent animal study investigated the effect of FGF‐2 in adjunction to collagen matrix (CM) for covering gingival recession. At 4 weeks, the FGF‐2+CM group showed significantly more root coverage and new cementum formation compared to the CM group. 14 Additionally, preliminary data from a pilot study showed that rhFGF‐2+CM significantly reduced the depth of RT1 recession defects 6 months postoperatively. 15 However, the efficacy of rhFGF‐2 in root coverage is yet not well investigated in clinical trials.
This case study documents the clinical application of rhFGF‐2‐treated CTG in root coverage for gingival defects caused by orthodontic treatments. The successful treatment outcome with rhFGF‐2 treated CTG may encourage researchers to further evaluate the efficacy of rhFGF‐2 in treating gingival recession in clinical trials.
MATERIALS AND METHODS
This case study consists of three cases of gingival recession on mandibular anterior teeth managed using rhFGF‐2 treated CTG by an experienced periodontist (Satoru Urano) in a private practice setting (Osaka, Japan). Patients’ information and treatment sequences are described in the Results section. All three patients signed written consents for the surgical treatment.
RESULTS
Case 1
A 27‐year‐old, systemically healthy Asian female was referred by her orthodontist in 2016. Her chief complaint was the gingival recession on tooth #25, which caused significant discomfort when brushing this area. Her orthodontic treatment started in 2014, however, the gingival recession on #25 became evident around 6 months before her visit for periodontal consultation. The initial periodontal examination revealed probing depth (PD) mostly ≤3 mm, whereas 4–5 mm PD was detected on the distal of #23 and #27. The recession depth on the buccal of #25 was 3 mm with papilla loss between #23 and #26 (Figure 1). Generalized bleeding on probing (BOP) and gingival swelling were noted due to the difficulty of plaque control induced by the existence of orthodontic appliances. Cone beam computed tomography (CBCT) imaging revealed varying amounts of buccal bone dehiscence on her mandibular anterior teeth. The cross‐section view of #25 indicated that the buccal bone loss extended almost to the root apex (Figure 2). Her periodontal diagnosis was generalized stage III grade B periodontitis, with RT2 gingival recession on #23–25. 16 Non‐surgical periodontal treatment and oral hygiene instructions were performed initially. Her periodontal condition was re‐evaluated 6 months later when her orthodontic treatment was completed. Full mouth PD was equal to or under 3 mm with minimal BOP (<10%). However, gingival recession became more evident on #23–25, ranging from 1 to 3 mm. Meanwhile, no keratinized tissue was detected on the buccal of #25. For this challenging condition, rhFGF‐2 treated CTG for root coverage via tunneling technique was treatment planned.
FIGURE 1.
Case 1: Initial presentation and re‐evaluation. (A) frontal view before the completion of orthodontic treatment (initial presentation) and (B) buccal view of mandibular anterior teeth after the completion of orthodontic treatment. (Re‐evaluation 6 months after non‐surgical treatment).
FIGURE 2.
Case 1: Initial radiographic assessment. (A) Frontal view of cone beam computed tomography (CBCT) and (B) the cross‐sectional view of #25.
After administration of local anesthesia,* the exposed root surface was thoroughly planed again. Classic tunnel preparation was initiated with intrasulcular incisions from #22 to #27. 17 The buccal gingiva was carefully elevated in a partial thickness fashion by sharp dissection extending apically beyond the mucogingival junction (Figure 3A,B). The interdental papillae were also elevated from the crestal bone. Thereafter, a CTG was harvested from the right side hard palate around the first molar and premolar area using a single‐incision technique. 18 The harvested CTG (20 × 7 × 1.5 mm) (Figure 3C) was soaked in rhFGF‐2 gel† in a dappen dish for 3 min and then inserted into the prepared tunnel. The buccal gingival tissue was coronally advanced to fully cover the CTG with a 6‐0 polypropylene suture‡ using a sling suture technique (Figure 3D). The standard postoperative protocol included analgesic§ and antimicrobial rinse∥ prescription and instructions of no mechanical plaque control at surgical sites until suture removal, typically 2–3 weeks postoperatively. The postoperative healing was uneventful, and sutures were removed from the site at 2 weeks after the surgery. The patient returned for postoperative examination and regular cleaning every 6 months up to 6 years. Figure 4 demonstrates the clinical outcome from 1 week to 6 years. The intraoral images of 3‐ and 6‐month follow‐ups revealed the gradual maturation of soft tissue healing with a detectable increase in tissue thickness. At the 6‐year follow‐up, significant gingival phenotype modification with complete root coverage was observed (Table 1). The interdental papilla between #25 and #26 was augmented as well. Meanwhile, the follow‐up CBCT (Figure 5) showed a stable buccal bone contour. The patient was able to brush her teeth without any discomfort and was satisfied with the aesthetic improvement.
FIGURE 3.
Case 1: Surgical management. (A) and (B) Tunnel preparation from #23 mesial side to #27 mesial side with interdental papilla reflection; (C) recombinant human fibroblast growth factor‐2 (rhFGF‐2) gel treated connective tissue graft (CTG) (20 × 7 × 1.5 mm); and (D) CTG recipient site wound closure using sling suture.
FIGURE 4.
Case 1: Postoperative clinical images of connective tissue graft (CTG) recipient site. (A) 1‐week, (B) 3‐month, (C) 6‐month, and (D) 6‐year follow‐ups.
TABLE 1.
Case 1: Initial and postoperative measurements of recession depth and keratinized tissue width (in mm).
| Tooth | 26 | 25 | 24 | 23 |
|---|---|---|---|---|
| RD (Buccal) | ||||
| Initial | 0 | 4 | 2 | 1 |
| 6 years | 0 | 1 | 0 | 0 |
| KTW (Buccal) | ||||
| Initial | 3 | 0 | 1 | 3 |
| 6 years | 3 | 4 | 4 | 4 |
Abbreviations: KTW, keratinized tissue width; RD, recession depth.
FIGURE 5.
Case 1: 6‐year postoperative radiographic assessment. (A) Frontal view of cone beam computed tomography (CBCT) and (B) the cross‐sectional view of #25.
Case 2
A 51‐year‐old Asian female presented in 2017 with a chief complaint of compromised esthetics after orthodontic treatment. Her medical history was significant for anxiety disorder, which was under medical control. She went through orthodontic treatment from 2013 to 2017 with extraction of #4, #13, #21, and #28. Progressive gingival recession was noted on the buccal and lingual sides of the mandibular anterior teeth. Full mouth periodontal charting showed all PDs were ≤3 mm. However, buccal and lingual gingival recession from #23 to #26 with interdental papilla loss was evident. The recession depth ranged from 2 to 3 mm. The gingival phenotype was thin with keratinized tissue width (KTW) of 1–2 mm and prominent bony exostoses (Figure 6). The diagnosis was periodontal health on a reduced periodontium with RT2 gingival recession. 16 CTG treated with rhFGF‐2 was planned for root coverage on both buccal and lingual sides. Lingual side root coverage was performed first using a classic tunneling technique, as described in the previous paragraph. The CTG was harvested using a single‐incision technique. 18 The harvested CTG was 20 × 7 × 1.5 mm in dimension and treated with rhFGF‐2 gel for 3 min before insertion into the tunnel. The wound was closed with a 6‐0 suture‡ (Figure 7A). Three months after the lingual procedure, buccal side root coverage was conducted using a modified coronally advanced tunnel (MCAT) 19 technique with rhFGF‐2 treated CTG. Briefly, after administration of local anesthesia and preoperative regional root planing, intrasulcular incisions were done from #22 to #27 buccally. A tunnel elevator was used to create a soft tissue tunnel with the extension beyond MGJ and underneath each interdental papilla for achieving tension‐free soft tissue mobility in a coronal direction (Figure 8A,B). The rhFGF‐2 treated CTG (20 × 7 × 1.5 mm) was inserted into the tunnel (Figure 8C). The wound was closed using a sling technique with a 6‐0 suture‡ (Figure 8D). The patient went through standard postoperative protocol uneventfully and was followed up to 2.5 years (Figure 9). The root coverage rate was nearly 100% on the lingual side 3 months postoperatively, and the outcome appeared stable for up to 2.5 years. Significant improvement was also noted on the buccal side of #23–26, with near‐complete root coverage achieved and successful gingival phenotype modification (Table 2). The patient returned for regular cleaning and examination every 6 months to maintain the treatment outcome.
FIGURE 6.
Case 2: Initial presentation. (A) Frontal and (B) lingual views of #23–26.
FIGURE 7.
Case 2: Surgical management of #23–26 lingual gingival recession. (A) Wound closure and (B) 3‐month postoperative follow‐up.
FIGURE 8.
Case 2: Surgical management of #23–26 buccal gingival recession. (A) Immediate pre‐operative buccal view of #23–26; (B) tunnel preparation from #23 to #26 with interdental papilla reflection; (C) recombinant human fibroblast growth factor‐2 (rhFGF‐2) treated connective tissue graft (CTG) (20 × 7 × 1.5 mm); and (D) CTG recipient site wound closure using sling suture.
FIGURE 9.
Case 2: Postoperative follow‐up after 2.5 years. (A) Frontal and (B) lingual views of #23–26.
TABLE 2.
Case 2: Initial and postoperative measurements of recession depth and keratinized tissue width (in mm).
| KTW (Lingual) | ||||
| Initial | 1 | 2 | 1 | 3 |
| 2.5 years | 2 | 2 | 2 | 3 |
| RD (Lingual) | ||||
| Initial | 2 | 2 | 3 | 0 |
| 2.5 years | 0 | 0 | 0 | 0 |
| Tooth | 26 | 25 | 24 | 23 |
|---|---|---|---|---|
| RD (Buccal) | ||||
| Initial | 2 | 3 | 2 | 0 |
| 2.5 years | 0 | 1 | 1 | 0 |
| KTW (Buccal) | ||||
| Initial | 1 | 0 | 0 | 2 |
| 2.5 years | 4 | 3 | 3 | 5 |
Abbreviations: KTW, keratinized tissue width; RD, recession depth.
Case 3
In 2023, a 32‐year‐old, systematically healthy Asian female presented with a chief complaint of gingival recession. Regarding the dental history, her orthodontic treatment was initiated in 2019. However, the patient stated that severe gingival recession on her mandibular anterior teeth was noted approximately 1 month prior to her periodontal consultation. Clinical examination revealed a healthy periodontium with all PDs ≤3 mm. Significant buccal gingival recession was noticed on #23–26. The recession depth of #25 and #26 was 5 and 3 mm respectively. Moreover, no keratinized tissue was detectable in this area (Figure 10A). The CBCT cross‐section views illustrated that #25 and 26 were mostly outside of the bone housing with significant apical root resorption (Figure 10B). The periodontal diagnosis was periodontal health on a reduced periodontium with RT2 gingival recession. 16 The treatment plan for these gingival defects was root coverage using rhFGF‐2 treated de‐epithelialized CTG via MCAT technique. The tunnel preparation was carried out in the same manner as that of Case 2. Two pieces of de‐epithelialized CTGs were harvested bilaterally from the hard palate and sutured together to form a long strip (Figure 10C). The joint graft was soaked in rhFGF‐2 gel for 3 min and then inserted into the tunnel space. The wound was closed using a sling technique (6‐0 polypropylene) to coronally advance the gingival margin (Figure 10D). The patient went through standard postoperative protocol uneventfully. Figure 11 demonstrates the clinical outcome at 3 and 6 months. The procedure resulted in complete root coverage on #23–26 with a gain of KTW and thickness (Table 3). The patient proceeded to continue her orthodontic treatment with mandibular first premolars extracted in April 2024. She was satisfied with the improvement and closely monitored every 3 months to assess the soft tissue condition while orthodontic tooth movement was underway.
FIGURE 10.
Case 3: Root coverage using recombinant human fibroblast growth factor‐2 (rhFGF‐2) treated connective tissue graft (CTG) for recession defects on #23–26. (A) Initial presentation for periodontal consultation 4 years after orthodontic treatment; (B) pre‐operative cone beam computed tomography (CBCT) cross‐sectional views on #26 (left) and #25 (right); (C) two pieces of CTG harvested from the right and left sides of the hard palate were sutured together; and (D) CTG recipient site wound closure using sling suture.
FIGURE 11.
Case 3: Postoperative clinical images of connective tissue graft (CTG) recipient site. (A) 3‐month and (B) 6‐month follow‐ups.
TABLE 3.
Case 3: Initial and postoperative measurements of recession depth and keratinized tissue width (in mm).
| Tooth | 26 | 25 | 24 | 23 |
|---|---|---|---|---|
| RD (Buccal) | ||||
| Initial | 4 | 5 | 1 | 3 |
| 6 months | 0 | 0 | 0 | 0 |
| KTW (Buccal) | ||||
| Initial | 0 | 0 | 2 | 0 |
| 6 months | 3 | 3 | 2 | 3 |
Abbreviations: KTW, keratinized tissue width; RD, recession depth.
DISCUSSION
This case study documents the application of rhFGF‐2‐treated CTG in root coverage for RT2 gingival defects caused by orthodontic tooth movement. These RT2 gingival defects, also classified as Miller Class III, were successfully managed with rhFGF‐2‐treated CTG via tunnel‐style techniques. Patients were satisfied with the improvements in esthetics and function. The treatment outcome seems to support that rhFGF‐2 could enhance the capability of soft tissue augmentation of CTG. This may also encourage more research to further evaluate the efficacy of this combination for treating relatively severe gingival recession in clinical trials.
Orthodontic tooth movement could be the primary etiology of these gingival defects since the three patients mentioned their gingival recession happened during or after their orthodontic treatment. Though their periodontal condition before orthodontic treatment was not provided by the referral, a thin periodontal phenotype could be a secondary etiology. For thin phenotype patients, phenotype modification therapy (PhMT) may create a more favorable environment for disease prevention, periodontal health maintenance, and resistance against gingival recession. Besides, PhMT via surgically facilitated orthodontic therapy may benefit patients by increasing the stability of orthodontic treatment outcomes, shortening the entire treatment time, expanding the boundary of tooth movement, and reducing the need for orthodontic camouflage. 20 , 21 This case study demonstrates that phenotype modification can be achieved with rhFGF‐2‐treated CTG after orthodontic treatment. Nevertheless, early PhMT should be considered if a thin periodontal phenotype can be identified during the pre‐orthodontic treatment evaluation.
The innovation of this case study stems from the root coverage material selection applied to challenging clinical cases. The gingival defects presented in this case study are classified RT2, with common features of papilla loss (interproximal attachment loss), buccal gingival recession, and minimal to no keratinized tissue. These gingival defects are considered challenging due to the combination of many unfavorable factors. A meta‐analysis reported that complete root coverage using various approaches for RT2 gingival defects could be achieved; however, the stability decreased significantly after 1 year. 22 Besides, there is still insufficient evidence to support which surgical modality is predictable for papilla augmentation. 23 Moreover, due to the patients’ history of orthodontic treatment, the buccal aspect of the roots was outside of alveolar bone housing with significant bone dehiscence. To improve treatment outcomes for these challenging gingival defects, the material selection for root coverage could be a decisive factor. Generally, CTG is considered the gold standard for treating RT1 recession defects. 8 , 24 However, for RT2 gingival defects, adding biologics to CTG could enhance the treatment result. Mercado et al. 4 reported that the addition of EMD to CTG improved the root coverage rate and the amount of KTW 36 months postoperatively for RT3 gingival defects. A recent study indicated that, compared to CTG alone, adding rhPDGF‐BB to CTG for treating RT2 gingival recession via MCAT achieved significantly higher mean root coverage and superior complete coverage rate. 25 FGF‐2 was tested in a clinical pilot study to evaluate the capability of root coverage. 15 In that study, rhFGF‐2 impregnated collagen membrane was used to treat RT1 gingival recession, and the researchers reported significant KTW gain and recession reduction after 6 months. To our knowledge, this case study is also one of the earliest clinical applications of rhFGF‐2 in root coverage, especially for RT2 defects. Due to the severity of gingival defects, rhFGF‐2‐treated CTG was selected instead of using collagen membrane as a carrier. This innovative modification seemed to enhance the capacity of CTG in soft tissue augmentation, which could be supported by the clinical findings including the significant recession reduction, KTW gain, and concomitant papilla augmentation from RT2 gingival defects.
The satisfactory treatment outcome could be attributed to the addition of rhFGF‐2 to CTG. It has been demonstrated that FGF‐2 can promote the proliferation and migration of periodontal ligament (PDL) cells, fibroblasts, and osteoblasts. FGF‐2 also facilitates angiogenesis and production of extracellular matrix, such as heparan sulfate, osteopontin, and macromolecular hyaluronan from PDL cells. These activities are important to wound healing since angiogenesis increases the regional blood supply, and the extracellular matrix offers mechanical support and anchorage for cells. 26 Thus, rhFGF‐2 could create a local environment suitable for CTG survival and further induce the reactions related to cell attachment and soft tissue regeneration.
The primary limitation of this study is the small number of patients with varying periods of follow‐up. More clinical trials are needed to validate the predictability of this approach. Moreover, there was neither standardized radiological assessment for all cases nor evidence‐based guidelines applied for esthetic evaluation. Due to its retrospective nature, surgical techniques applied in this case study were not unified, and some measurements, such as papilla height and gingival thickness, were not quantitatively recorded.
CONCLUSION
Root coverage for challenging RT2 gingival recession defects using rhFGF‐2 treated CTG resulted in satisfactory esthetics, functional improvements, and successful gingival phenotype modification for long‐term stability of periodontal health.
AUTHOR CONTRIBUTIONS
Guo‐Liang Cheng: Conceptualization; writing—original draft; writing—review & editing, and visualization. Satoru Urano: Conceptualization; resources; writing—original draft, and writing—review & editing. Yu‐Chang Wu: Conceptualization and writing—review & editing. Rami Alsabbagh: Writing—review & editing. Hsun‐Liang Chan: Conceptualization and writing—review & editing.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Cheng G‐L, Urano S, Wu Y‐C, Alsabbagh R, Chan H‐L. Root coverage using recombinant human fibroblast growth factor‐2 treated connective tissue graft: Case studies. Clin Adv Periodontics. 2025;15:354–363. 10.1002/cap.10323
Footnotes
ORA Injection Dental Cartridge, GC Showayakuhinn Corporation, Tokyo, Japan.
REGROTH, KAKEN Pharmaceutical Co., Ltd., Tokyo, Japan.
PROLENE, ETHICON, Johnson & Johnson, New Brunswick, NJ.
Loxoprofen Sodium Hydrate, DAICHI SANKYO COMPANY, Tokyo, Japan.
Systema SP‐T Medical gargle, Lion Dental Products Co., Ltd., Tokyo, Japan.
DATA AVAILABILITY STATEMENT
The data in support of the findings in this case study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data in support of the findings in this case study are available from the corresponding author upon reasonable request.