Abstract
Objectives
To investigate the effect of epithelial growth factor (EGF) with collagen matrix (CM) on the gain of KT for buccally positioned implants in dogs.
Materials and methods
In five dogs, four implants were placed buccally with the whole part of KT excision on the buccal side (two implants per each hemi-mandible). After one month, KT augmentation was performed: 1) free gingival grafts (FGG), 2) collagen matrix (CM) only, 3) CM soaked with 1 μg/g of EGF, and 4) CM soaked with 10 μg/g of EGF (n = 5 in each group). The experimental animals were sacrificed three months post-KT augmentation. Clinical, histologic, and histomorphometric analyses were performed.
Results
The clinical KT zone was the highest in group FGG (5.16 ± 1.63 mm). Histologically, all groups presented buccal bony dehiscence. Regarding newly formed KT, no specific difference was found among the groups, but robust rete pegs formation in some specimens in group FGG. Histomorphometric KT height (4.66 ± 1.81 mm) and length (5.56 ± 2.25 mm) were the highest in group FGG, whereas similar increases were noted in the rest. The buccal soft tissue thickness at the coronal part of the implant did not exceed 2 mm in all groups.
Conclusion
All groups presented increased KT zone, but FGG treatment was more favored. The addition of EGF to CM appeared not to enhance KT formation.
Clinical relevance
FGG treatment was more favorable to re-establish the KT zone than other treatment modalities.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Monje A, Insua A and Wang HL (2019) Understanding Peri-Implantitis as a Plaque-Associated and Site-Specific Entity: On the Local Predisposing Factors. J Clin Med 8:279. https://doi.org/10.3390/jcm8020279
Bouri A Jr, Bissada N, Al-Zahrani MS, Faddoul F, Nouneh I (2008) Width of keratinized gingiva and the health status of the supporting tissues around dental implants. Int J Oral Maxillofac Implants 23:323–326
Boynuegri D, Nemli SK, Kasko YA (2013) Significance of keratinized mucosa around dental implants: a prospective comparative study. Clin Oral Implants Res 24:928–933. https://doi.org/10.1111/j.1600-0501.2012.02475.x
Oh SL, Ji C, Azad S (2020) Free gingival grafts for implants exhibiting a lack of keratinized mucosa: Extended follow-up of a randomized controlled trial. J Clin Periodontol 47:777–785. https://doi.org/10.1111/jcpe.13272
Oh SL, Masri RM, Williams DA, Ji C, Romberg E (2017) Free gingival grafts for implants exhibiting lack of keratinized mucosa: a prospective controlled randomized clinical study. J Clin Periodontol 44:195–203. https://doi.org/10.1111/jcpe.12660
Park JS, Herr Y, Chung JH, Shin SI, Lim HC (2022) Retrospective analysis of keratinized tissue augmentation using a xenogeneic collagen matrix for resolving peri-implant mucositis and peri-implantitis. J Periodontal Implant Sci. https://doi.org/10.5051/jpis.2200700035
Roccuzzo M, Grasso G, Dalmasso P (2016) Keratinized mucosa around implants in partially edentulous posterior mandible: 10-year results of a prospective comparative study. Clin Oral Implants Res 27:491–496. https://doi.org/10.1111/clr.12563
Schrott AR, Jimenez M, Hwang JW, Fiorellini J, Weber HP (2009) Five-year evaluation of the influence of keratinized mucosa on peri-implant soft-tissue health and stability around implants supporting full-arch mandibular fixed prostheses. Clin Oral Implants Res 20:1170–1177. https://doi.org/10.1111/j.1600-0501.2009.01795.x
Souza AB, Tormena M, Matarazzo F, Araujo MG (2016) The influence of peri-implant keratinized mucosa on brushing discomfort and peri-implant tissue health. Clin Oral Implants Res 27:650–655. https://doi.org/10.1111/clr.12703
Thoma DS, Benic GI, Zwahlen M, Hammerle CH, Jung RE (2009) A systematic review assessing soft tissue augmentation techniques. Clin Oral Implants Res 20(Suppl 4):146–165. https://doi.org/10.1111/j.1600-0501.2009.01784.x
Lim HC, An SC, Lee DW (2018) A retrospective comparison of three modalities for vestibuloplasty in the posterior mandible: apically positioned flap only vs. free gingival graft vs. collagen matrix. Clin Oral Investig 22:2121–2128. https://doi.org/10.1007/s00784-017-2320-y
Lorenzo R, Garcia V, Orsini M, Martin C, Sanz M (2012) Clinical efficacy of a xenogeneic collagen matrix in augmenting keratinized mucosa around implants: a randomized controlled prospective clinical trial. Clin Oral Implants Res 23:316–324. https://doi.org/10.1111/j.1600-0501.2011.02260.x
Sanz M, Lorenzo R, Aranda JJ, Martin C, Orsini M (2009) Clinical evaluation of a new collagen matrix (Mucograft prototype) to enhance the width of keratinized tissue in patients with fixed prosthetic restorations: a randomized prospective clinical trial. J Clin Periodontol 36:868–876. https://doi.org/10.1111/j.1600-051X.2009.01460.x
Tarasenko S, Ashurko I, Taschieri S, Repina S, Esaya NA, Corbella S (2020) Comparative analysis of methods to increase the amount of keratinized mucosa before stage-two surgery: a randomized controlled study. Quintessence Int 51:374–387. https://doi.org/10.3290/j.qi.a44216
Thoma DS, Alshihri A, Fontolliet A, Hammerle CHF, Jung RE, Benic GI (2018) Clinical and histologic evaluation of different approaches to gain keratinized tissue prior to implant placement in fully edentulous patients. Clin Oral Investig 22:2111–2119. https://doi.org/10.1007/s00784-017-2319-4
Ben Amara H, Thoma DS, Schwarz F, Song HY, Capetillo J, Koo KT (2019) Healing kinetics of oral soft tissue wounds treated with recombinant epidermal growth factor: Translation from a canine model. J Clin Periodontol 46:105–117. https://doi.org/10.1111/jcpe.13035
Kim JM, Bak EJ, Chang JY, Kim ST, Park WS, Yoo YJ, Cha JH (2011) Effects of HB-EGF and epiregulin on wound healing of gingival cells in vitro. Oral Dis 17:785–793. https://doi.org/10.1111/j.1601-0825.2011.01836.x
Pansani TN, Basso FG, Turrioni AP, Soares DG, Hebling J, de Souza Costa CA (2017) Effects of low-level laser therapy and epidermal growth factor on the activities of gingival fibroblasts obtained from young or elderly individuals. Lasers Med Sci 32:45–52. https://doi.org/10.1007/s10103-016-2081-x
Park JW, Hwang SR and Yoon IS (2017) Advanced growth factor delivery systems in wound management and skin regeneration. Molecules 22:1259. https://doi.org/10.3390/molecules22081259
Bui TQ, Bui QVP, Nemeth D, Hegyi P, Szakacs Z, Rumbus Z, Toth B, Emri G, Parniczky A, Sarlos P and Varga O (2019) Epidermal growth factor is effective in the treatment of diabetic foot ulcers: meta-analysis and systematic review. Int J Environ Res Public Health 16:2584. https://doi.org/10.3390/ijerph16142584
Kaya O, Orhan E, Sapmaz-Metin M, Topcu-Tarladacalisir Y, Gunduz O, Aydin B (2020) The effects of epidermal growth factor on early burn-wound progression in rats. Dermatol Ther 33:e13196. https://doi.org/10.1111/dth.13196
Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, Wu FZ, Cheng Y, Xiang LJ, Guo DJ, Luo X, Zhang GY, Fu XB, Bellusci S, Li XK, Xiao J (2013) The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS ONE 8:e59966. https://doi.org/10.1371/journal.pone.0059966
Zhao Z, Lv D, Zhang B, Yong L, Zhang R, Wang X (2022) Efficacy of Human-Recombinant Epidermal Growth Factor Combined with Povidone-Iodine for Pressure Ulcers and Its Influence on Inflammatory Cytokines. Mediators Inflamm 2022:3878320. https://doi.org/10.1155/2022/3878320
Kim JW, Kim MG, Lee HJ, Koh Y, Kwon JH, Kim I, Park S, Kim BK, Oh JM, Kim KI, Yoon SS (2017) Topical Recombinant Human Epidermal Growth Factor for Oral Mucositis Induced by Intensive Chemotherapy with Hematopoietic Stem Cell Transplantation: Final Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial. PLoS ONE 12:e0168854. https://doi.org/10.1371/journal.pone.0168854
Kim KI, Kim JW, Lee HJ, Kim BS, Bang SM, Kim I, Oh JM, Yoon SS, Lee JS, Park S, Kim BK (2013) Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation. Am J Hematol 88:107–112. https://doi.org/10.1002/ajh.23359
Wu HG, Song SY, Kim YS, Oh YT, Lee CG, Keum KC, Ahn YC, Lee SW (2009) Therapeutic effect of recombinant human epidermal growth factor (RhEGF) on mucositis in patients undergoing radiotherapy, with or without chemotherapy, for head and neck cancer: a double-blind placebo-controlled prospective phase 2 multi-institutional clinical trial. Cancer 115:3699–3708. https://doi.org/10.1002/cncr.24414
Stefanini M, Rendon A, Zucchelli A (2000) Sangiorgi M and Zucchelli G (2023) Avoiding errors and complications related to immediate implant placement in the esthetic area with a mucogingival approach. Periodontol 92:362–372. https://doi.org/10.1111/prd.12491
Stefanini M, Marzadori M, Sangiorgi M, Rendon A (2000) Testori T and Zucchelli G (2023) Complications and treatment errors in peri-implant soft tissue management. Periodontol 92:263–277. https://doi.org/10.1111/prd.12470
Romandini M, Pedrinaci I, Lima C, Soldini MC, Araoz A, Sanz M (2021) Prevalence and risk/protective indicators of buccal soft tissue dehiscence around dental implants. J Clin Periodontol 48:455–463. https://doi.org/10.1111/jcpe.13417
Herrera D, Berglundh T, Schwarz F, Chapple I, Jepsen S, SculeanKebschull AM, Papapanou PN, Tonetti MS, Sanz M, participants EFPw and methodological c (2023) Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline. J Clin Periodontol 50(Suppl 26):4–76. https://doi.org/10.1111/jcpe.13823
Thoma DS, Lim HC, Paeng KW, Kim MJ, Jung RE, Hammerle CHF, Jung UW (2020) Augmentation of keratinized tissue at tooth and implant sites by using autogenous grafts and collagen-based soft-tissue substitutes. J Clin Periodontol 47:64–71. https://doi.org/10.1111/jcpe.13194
Monje A, Chappuis V, Monje F, Munoz F, Wang HL, Urban IA, Buser D (2019) The Critical Peri-implant Buccal Bone Wall Thickness Revisited: An Experimental Study in the Beagle Dog. Int J Oral Maxillofac Implants 34:1328–1336. https://doi.org/10.11607/jomi.7657
Imber JC, Roccuzzo A, Stahli A, Bosshardt DD, Munoz F, Ramseier CA, Lang NP, Sculean A (2023) Spontaneous regeneration of keratinized tissue at implants and teeth. J Clin Periodontol 50:1064–1074. https://doi.org/10.1111/jcpe.13820
Karring T, Lang NP, Loe H (1975) The role of gingival connective tissue in determining epithelial differentiation. J Periodontal Res 10:1–11. https://doi.org/10.1111/j.1600-0765.1975.tb00001.x
Pereira Neto AR, Passoni BB, de Souza JM, de Souza JGO, Benfatti CA, MaginiRde S, Bianchini MA (2014) Creeping attachment involving dental implants: two case reports with a two-year follow-up from an ongoing clinical study. Case Rep Dent 2014:756908. https://doi.org/10.1155/2014/756908
Oh SL, Chung MK (2020) Creeping attachment following free gingival grafts around dental implants exhibiting mucosal recession with a lack of keratinised mucosa: A case series. Int J Oral Implantol (Berl) 13:401–409
Yildirim S, Ozener HO, Dogan B, Kuru B (2018) Effect of topically applied hyaluronic acid on pain and palatal epithelial wound healing: An examiner-masked, randomized, controlled clinical trial. J Periodontol 89:36–45. https://doi.org/10.1902/jop.2017.170105
Noguchi S, Ohba Y, Oka T (1991) Effect of salivary epidermal growth factor on wound healing of tongue in mice. Am J Physiol 260:E620–E625. https://doi.org/10.1152/ajpendo.1991.260.4.E620
Sonis ST, Costa JW Jr, Evitts SM, Lindquist LE, Nicolson M (1992) Effect of epidermal growth factor on ulcerative mucositis in hamsters that receive cancer chemotherapy. Oral Surg Oral Med Oral Pathol 74:749–755. https://doi.org/10.1016/0030-4220(92)90402-c
Avila-Ortiz G, Gonzalez-Martin O, Couso-Queiruga E, Wang HL (2020) The peri-implant phenotype. J Periodontol 91:283–288. https://doi.org/10.1002/JPER.19-0566
Jung RE, Holderegger C, Sailer I, Khraisat A, Suter A, Hammerle CH (2008) The effect of all-ceramic and porcelain-fused-to-metal restorations on marginal peri-implant soft tissue color: a randomized controlled clinical trial. Int J Periodontics Restorative Dent 28:357–365
Galarraga-Vinueza ME, Tavelli L (2023) Soft tissue features of peri-implant diseases and related treatment. Clin Implant Dent Relat Res 25:661–681. https://doi.org/10.1111/cid.13156
Thoma DS, Gil A (2000) Hammerle CHF and Jung RE (2022) Management and prevention of soft tissue complications in implant dentistry. Periodontol 88:116–129. https://doi.org/10.1111/prd.12415
Acknowledgements
DAEWOONG, Seoul, Korea, kindly provided epidermal growth factor. Genoss, Suwon, Korea, kindly provided dental implants and collagen matrix.
Funding
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2020R1C1C1008201).
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Conceptualization: Hyun-Chang Lim, Jong-Hyuk Chung; Methodology: Seung-Yun Shin, Hyun-Chang Lim; Formal analysis and investigation: Chang-Hoon Kim, Heejun Yoon, Sunmin Lee; Writing - original draft preparation: Chang-Hoon Kim, Heejun Yoon; Writing - review and editing: Hyun-Chang Lim, Jong-Hyuk Chung; Supervision: Seung-Yun Shin.
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Lim, HC., Kim, CH., Yoon, H. et al. Keratinized tissue augmentation using collagen-based soft tissue substitute with/without epidermal growth factor on buccally positioned implants: a pilot preclinical study. Clin Oral Invest 27, 7899–7908 (2023). https://doi.org/10.1007/s00784-023-05382-8
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DOI: https://doi.org/10.1007/s00784-023-05382-8