Efficacy of biologics for alveolar ridge preservation/reconstruction and implant site development: An American Academy of Periodontology best evidence systematic review

Fernando Suárez-López Del Amo, Alberto Monje, Fernando Suárez-López Del Amo, Alberto Monje

Abstract

Background: The use of biologics may be indicated for alveolar ridge preservation (ARP) and reconstruction (ARR), and implant site development (ISD). The present systematic review aimed to analyze the effect of autologous blood-derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet-derived growth factor-BB (rhPDGF-BB), and recombinant human bone morphogenetic protein-2 (rhBMP-2), on the outcomes of ARP/ARR and ISD therapy (i.e., alveolar ridge augmentation [ARA] and maxillary sinus floor augmentation [MSFA]).

Methods: An electronic search for eligible articles published from January 2000 to October 2021 was conducted. Randomized clinical trials evaluating the efficacy of ABPs, EMD, rhBMP-2, and rhPDGF-BB for ARP/ARR and ISD were included according to pre-established eligibility criteria. Data on linear and volumetric dimensional changes, histomorphometric findings, and a variety of secondary outcomes (i.e., clinical, implant-related, digital imaging, safety, and patient-reported outcome measures [PROMs]) were extracted and critically analyzed. Risk of bias assessment of the selected investigations was also conducted.

Results: A total of 39 articles were included and analyzed qualitatively. Due to the high level of heterogeneity across studies, quantitative analyses were not feasible. Most studies in the topic of ARP/ARR revealed that the use of biologics rendered similar results compared with conventional protocols. However, when juxtaposed to unassisted healing or socket filling using collagen sponges, the application of biologics did contribute to attenuate post-extraction alveolar ridge atrophy in most investigations. Additionally, histomorphometric outcomes were positively influenced by the application of biologics. The use of biologics in ARA interventions did not yield superior clinical or radiographic outcomes compared with control therapies. Nevertheless, ABPs enhanced new bone formation and reduced the likelihood of early wound dehiscence. The use of biologics in MSFA interventions did not translate into superior clinical or radiographic outcomes. It was observed, though, that the use of some biologics may promote bone formation during earlier stages of healing. Only four clinical investigations evaluated PROMs and reported a modest beneficial impact of the use of biologics on pain and swelling. No severe adverse events in association with the use of the biologics evaluated in this systematic review were noted.

Conclusions: Outcomes of therapy after post-extraction ARP/ARR and ARA in edentulous ridges were comparable among different therapeutic modalities evaluated in this systematic review. Nevertheless, the use of biologics (i.e., PRF, EMD, rhPDGF-BB, and rhBMP-2) in combination with a bone graft material generally results into superior histomorphometric outcomes and faster wound healing compared with control groups.

Keywords: alveolar ridge augmentation; dental implants; jaw, edentulous; sinus floor augmentation.

Conflict of interest statement

The authors have no conflicts of interest related to this systematic review.

© 2021 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.

Figures

FIGURE 1
FIGURE 1
PRISMA flowchart

References

    1. Chappuis V, Buser R, Bragger U, Bornstein MM, Salvi GE, Buser D. Long‐term outcomes of dental implants with a titanium plasma‐sprayed surface: a 20‐year prospective case series study in partially edentulous patients. Clin Implant Dent Relat Res 2013;15:780‐790.
    1. Moraschini V, Poubel LA, Ferreira VF, Barboza Edos S. Evaluation of survival and success rates of dental implants reported in longitudinal studies with a follow‐up period of at least 10 years: a systematic review. Int J Oral Maxillofac Surg 2015;44:377‐388.
    1. Araujo MG, da Silva JCC, de Mendonca AF, Lindhe J. Ridge alterations following grafting of fresh extraction sockets in man. A randomized clinical trial. Clin Oral Implants Res 2015;26:407‐412.
    1. Lee JS, Shin HK, Yun JH, Cho KS. Randomized clinical trial of maxillary sinus grafting using deproteinized porcine and bovine bone mineral. Clin Implant Dent Relat Res 2017;19:140‐150.
    1. Mendoza‐Azpur G, de la Fuente A, Chavez E, Valdivia E, Khouly I. Horizontal ridge augmentation with guided bone regeneration using particulate xenogenic bone substitutes with or without autogenous block grafts: a randomized controlled trial. Clin Implant Dent Relat Res 2019;21:521‐530.
    1. Urban IA, Lozada JL, Jovanovic SA, Nagursky H, Nagy K. Vertical ridge augmentation with titanium‐reinforced, dense‐PTFE membranes and a combination of particulated autogenous bone and anorganic bovine bone‐derived mineral: a prospective case series in 19 patients. Int J Oral Maxillofac Implants 2014;29:185‐193.
    1. Avila‐Ortiz G, Bartold PM, Giannobile W, et al. Biologics and cell therapy tissue engineering approaches for the management of the edentulous maxilla: a systematic review. Int J Oral Maxillofac Implants 2016;31(Suppl):s121‐164.
    1. Suarez‐Lopez Del Amo F, Monje A, Padial‐Molina M, Tang Z, Wang HL. Biologic agents for periodontal regeneration and implant site development. Biomed Res Int 2015;2015:957518.
    1. Mercado F, Vaquette C, Hamlet S, Ivanovski S. Enamel matrix derivative promotes new bone formation in xenograft assisted maxillary anterior ridge preservation‐A randomized controlled clinical trial. Clin Oral Implants Res 2021;32:732‐744.
    1. Eskan MA, Greenwell H, Hill M, et al. Platelet‐rich plasma‐assisted guided bone regeneration for ridge augmentation: a randomized, controlled clinical trial. J Periodontol 2014;85:661‐668.
    1. Lee JH, Kim DH, Jeong SN. Comparative assessment of anterior maxillary alveolar ridge preservation with and without adjunctive use of enamel matrix derivative: a randomized clinical trial. Clin Oral Implants Res 2020;31:1‐9.
    1. Torres J, Tamimi F, Alkhraisat MH, et al. Platelet‐rich plasma may prevent titanium‐mesh exposure in alveolar ridge augmentation with anorganic bovine bone. J Clin Periodontol 2010;37:943‐951.
    1. Higgins JPT, thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 62 (updated February 2021); 2021.
    1. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg 2021;88:105906.
    1. Ortega‐Mejia H, Estrugo‐Devesa A, Saka‐Herran C, Ayuso‐Montero R, Lopez‐Lopez J, Velasco‐Ortega E. Platelet‐rich plasma in maxillary sinus augmentation: systematic review. Materials (Basel) 2020;13.
    1. Liu R, Yan M, Chen S, Huang W, Wu D, Chen J. Effectiveness of platelet‐rich fibrin as an adjunctive material to bone graft in maxillary sinus augmentation: a meta‐analysis of randomized controlled trails. Biomed Res Int 2019;2019:7267062.
    1. Miron RJ, Fujioka‐Kobayashi M, Moraschini V, Zhang Y, Gruber R, Wang HL. Efficacy of platelet‐rich fibrin on bone formation, part 1: alveolar ridge preservation. Int J Oral Implantol (Berl) 2021;14:181‐194.
    1. Fujioka‐Kobayashi M, Miron RJ, Moraschini V, Zhang Y, Gruber R, Wang HL. Efficacy of platelet‐rich fibrin on bone formation, part 2: guided bone regeneration, sinus elevation and implant therapy. Int J Oral Implantol (Berl) 2021;14:285‐302.
    1. Tavelli L, Ravida A, Barootchi S, Chambrone L, Giannobile WV. Recombinant human platelet‐derived growth factor: a systematic review of clinical findings in oral regenerative procedures. JDR Clin Trans Res 2021;6:161‐173.
    1. Avila‐Ortiz G, Chambrone L, Vignoletti F. Effect of alveolar ridge preservation interventions following tooth extraction: a systematic review and meta‐analysis. J Clin Periodontol 2019;46(Suppl 21):195‐223.
    1. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
    1. Chambrone L, Ramos UD, Reynolds MA. Infrared lasers for the treatment of moderate to severe periodontitis: an American Academy of Periodontology best evidence review. J Periodontol 2018;89:743‐765.
    1. ADA . American Dental Association (ADA) Clinical Practice Guidelines Handbook. ADA; 2013; Accessed May 1, 2021.
    1. Areewong K, Chantaramungkorn M, Khongkhunthian P. Platelet‐rich fibrin to preserve alveolar bone sockets following tooth extraction: a randomized controlled trial. Clin Implant Dent Relat Res 2019;21:1156‐1163.
    1. Canellas J, da Costa RC, Breves RC, et al. Tomographic and histomorphometric evaluation of socket healing after tooth extraction using leukocyte‐ and platelet‐rich fibrin: a randomized, single‐blind, controlled clinical trial. J Craniomaxillofac Surg 2020;48:24‐32.
    1. Clark D, Rajendran Y, Paydar S, et al. Advanced platelet‐rich fibrin and freeze‐dried bone allograft for ridge preservation: a randomized controlled clinical trial. J Periodontol 2018;89:379‐387.
    1. Girish Kumar N, Chaudhary R, Kumar I, Arora SS, Kumar N, Singh H. To assess the efficacy of socket plug technique using platelet rich fibrin with or without the use of bone substitute in alveolar ridge preservation: a prospective randomised controlled study. Oral Maxillofac Surg 2018;22:135‐142.
    1. Stumbras A, Galindo‐Moreno P, Januzis G, Juodzbalys G. Three‐dimensional analysis of dimensional changes after alveolar ridge preservation with bone substitutes or plasma rich in growth factors: Randomized and controlled clinical trial. Clin Implant Dent Relat Res 2021;23:96‐106.
    1. Stumbras A, Januzis G, Gervickas A, Kubilius R, Juodzbalys G. Randomized and controlled clinical trial of bone healing after alveolar ridge preservation using xenografts and allografts versus plasma rich in growth factors. J Oral Implantol 2020;46:515‐525.
    1. Lin SC, Li X, Liu H, et al. Clinical applications of concentrated growth factors combined with bone substitutes for alveolar ridge preservation in maxillary molar area: a randomized controlled trial. Int J Implant Dent 2021;7:115.
    1. Alzahrani AA, Murriky A, Shafik S. Influence of platelet rich fibrin on post‐extraction socket healing: A clinical and radiographic study. Saudi Dent J 2017;29:149‐155.
    1. Coomes AM, Mealey BL, Huynh‐Ba G, Barboza‐Arguello C, Moore WS, Cochran DL. Buccal bone formation after flapless extraction: a randomized, controlled clinical trial comparing recombinant human bone morphogenetic protein 2/absorbable collagen carrier and collagen sponge alone. J Periodontol 2014;85:525‐535.
    1. Kim YJ, Lee JY, Kim JE, Park JC, Shin SW, Cho KS. Ridge preservation using demineralized bone matrix gel with recombinant human bone morphogenetic protein‐2 after tooth extraction: a randomized controlled clinical trial. J Oral Maxillofac Surg 2014;72:1281‐1290.
    1. Fiorellini JP, Howell TH, Cochran D, et al. Randomized study evaluating recombinant human bone morphogenetic protein‐2 for extraction socket augmentation. J Periodontol 2005;76:605‐613.
    1. Huh JB, Lee HJ, Jang JW, et al. Randomized clinical trial on the efficacy of Escherichia coli‐derived rhBMP‐2 with beta‐TCP/HA in extraction socket. J Adv Prosthodont 2011;3:161‐165.
    1. Badakhshan S, Badakhshan A, Badakhshan S, et al. Clinical and radiographic assessments of tooth socket preservation using leukocyte platelet‐rich fibrin. J Long Term Eff Med Implants 2020;30:13‐19.
    1. Castro AB, Van Dessel J, Temmerman A, Jacobs R, Quirynen M. Effect of different platelet‐rich fibrin matrices for ridge preservation in multiple tooth extractions: A split‐mouth randomized controlled clinical trial. J Clin Periodontol 2021;48:984‐995.
    1. Suttapreyasri S, Leepong N. Influence of platelet‐rich fibrin on alveolar ridge preservation. J Craniofac Surg 2013;24:1088‐1094.
    1. Temmerman A, Vandessel J, Castro A, et al. The use of leucocyte and platelet‐rich fibrin in socket management and ridge preservation: a split‐mouth, randomized, controlled clinical trial. J Clin Periodontol 2016;43:990‐999.
    1. Hartlev J, Spin‐Neto R, Schou S, Isidor F, Norholt SE. Cone beam computed tomography evaluation of staged lateral ridge augmentation using platelet‐rich fibrin or resorbable collagen membranes in a randomized controlled clinical trial. Clin Oral Implants Res 2019;30:277‐284.
    1. Isik G, Ozden Yuce M, Kocak‐Topbas N, Gunbay T. Guided bone regeneration simultaneous with implant placement using bovine‐derived xenograft with and without liquid platelet‐rich fibrin: a randomized controlled clinical trial. Clin Oral Investig 2021;25:5563‐5575.
    1. Santana RB, Santana CM. A clinical comparison of guided bone regeneration with platelet‐derived growth factor‐enhanced bone ceramic versus autogenous bone block grafting. Int J Oral Maxillofac Implants 2015;30:700‐706.
    1. Thoma DS, Payer M, Jakse N, et al. Randomized, controlled clinical two‐centre study using xenogeneic block grafts loaded with recombinant human bone morphogenetic protein‐2 or autogenous bone blocks for lateral ridge augmentation. J Clin Periodontol 2018;45:265‐276.
    1. Nam JW, Khureltogtokh S, Choi HM, Lee AR, Park YB, Kim HJ. Randomised controlled clinical trial of augmentation of the alveolar ridge using recombinant human bone morphogenetic protein 2 with hydroxyapatite and bovine‐derived xenografts: comparison of changes in volume. Br J Oral Maxillofac Surg 2017;55:822‐829.
    1. Jung RE, Windisch SI, Eggenschwiler AM, Thoma DS, Weber FE, Hammerle CH. A randomized‐controlled clinical trial evaluating clinical and radiological outcomes after 3 and 5 years of dental implants placed in bone regenerated by means of GBR techniques with or without the addition of BMP‐2. Clin Oral Implants Res 2009;20:660‐666.
    1. de Freitas RM, Susin C, Spin‐Neto R, et al. Horizontal ridge augmentation of the atrophic anterior maxilla using rhBMP‐2/ACS or autogenous bone grafts: a proof‐of‐concept randomized clinical trial. J Clin Periodontol 2013;40:968‐975.
    1. de Almeida Barros Mourao CF, Lourenco ES, Nascimento JRB, et al. Does the association of blood‐derived growth factors to nanostructured carbonated hydroxyapatite contributes to the maxillary sinus floor elevation? A randomized clinical trial. Clin Oral Investig 2019;23:369‐379.
    1. Bettega G, Brun JP, Boutonnat J, et al. Autologous platelet concentrates for bone graft enhancement in sinus lift procedure. Transfusion 2009;49:779‐785.
    1. Froum SJ, Wallace S, Cho SC, et al. A histomorphometric comparison of Bio‐Oss alone versus Bio‐Oss and platelet‐derived growth factor for sinus augmentation: a postsurgical assessment. Int J Periodontics Restorative Dent 2013;33:269‐279.
    1. Nizam N, Eren G, Akcali A, Donos N. Maxillary sinus augmentation with leukocyte and platelet‐rich fibrin and deproteinized bovine bone mineral: a split‐mouth histological and histomorphometric study. Clin Oral Implants Res 2018;29:67‐75.
    1. Pichotano EC, de Molon RS, de Souza RV, Austin RS, Marcantonio E, Zandim‐Barcelos DL. Evaluation of L‐PRF combined with deproteinized bovine bone mineral for early implant placement after maxillary sinus augmentation: a randomized clinical trial. Clin Implant Dent Relat Res 2019;21:253‐262.
    1. Froum SJ, Wallace S, Cho SC, et al. Histomorphometric comparison of different concentrations of recombinant human bone morphogenetic protein with allogeneic bone compared to the use of 100% mineralized cancellous bone allograft in maxillary sinus grafting. Int J Periodontics Restorative Dent 2013;33:721‐730.
    1. Cho YS, Hwang KG, Jun SH, Tallarico M, Kwon AM, Park CJ. Radiologic comparative analysis between saline and platelet‐rich fibrin filling after hydraulic transcrestal sinus lifting without adjunctive bone graft: a randomized controlled trial. Clin Oral Implants Res 2020;31:1087‐1093.
    1. Zhang Y, Tangl S, Huber CD, Lin Y, Qiu L, Rausch‐Fan X. Effects of Choukroun's platelet‐rich fibrin on bone regeneration in combination with deproteinized bovine bone mineral in maxillary sinus augmentation: a histological and histomorphometric study. J Craniomaxillofac Surg 2012;40:321‐328.
    1. Wiltfang J, Schlegel KA, Schultze‐Mosgau S, Nkenke E, Zimmermann R, Kessler P. Sinus floor augmentation with beta‐tricalciumphosphate (beta‐TCP): does platelet‐rich plasma promote its osseous integration and degradation? Clin Oral Implants Res 2003;14:213‐218.
    1. Boyne PJ, Lilly LC, Marx RE, et al. De novo bone induction by recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in maxillary sinus floor augmentation. J Oral Maxillofac Surg 2005;63:1693‐1707.
    1. Kim HJ, Chung JH, Shin SY, et al. Efficacy of rhBMP‐2/hydroxyapatite on sinus floor augmentation: a multicenter, randomized controlled clinical trial. J Dent Res 2015;94:158S‐165S.
    1. Triplett RG, Nevins M, Marx RE, et al. Pivotal, randomized, parallel evaluation of recombinant human bone morphogenetic protein‐2/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation. J Oral Maxillofac Surg 2009;67:1947‐1960.
    1. Comert Kilic S, Gungormus M, Parlak SN. Histologic and histomorphometric assessment of sinus‐floor augmentation with beta‐tricalcium phosphate alone or in combination with pure‐platelet‐rich plasma or platelet‐rich fibrin: a randomized clinical trial. Clin Implant Dent Relat Res 2017;19:959‐967.
    1. Boyne PJ, James RA. Grafting of the maxillary sinus floor with autogenous marrow and bone. J Oral Surg 1980;38:613‐616.
    1. Strauss FJ, Stahli A, Gruber R. The use of platelet‐rich fibrin to enhance the outcomes of implant therapy: a systematic review. Clin Oral Implants Res 2018;29(Suppl 18):6‐19.
    1. Miron RJ, Fujioka‐Kobayashi M, Bishara M, Zhang Y, Hernandez M, Choukroun J. Platelet‐rich fibrin and soft tissue wound healing: a systematic review. Tissue Eng Part B Rev 2017;23:83‐99.
    1. Alarcon MA, Diaz KT, Aranda L, Cafferata EA, Faggion CM, Jr. , Monje A. Use of biologic agents to promote bone formation in implant dentistry: a critical assessment of systematic reviews. Int J Oral Maxillofac Implants 2017;32:271‐281.
    1. Lynch SE, Wisner‐Lynch L, Nevins M, Nevins ML. A new era in periodontal and periimplant regeneration: use of growth‐factor enhanced matrices incorporating rhPDGF. Compend Contin Educ Dent 2006;27:672‐678.
    1. Ronnstrand L, Heldin CH. Mechanisms of platelet‐derived growth factor‐induced chemotaxis. Int J Cancer 2001;91:757‐762.
    1. Boyapati L, Wang HL. The role of platelet‐rich plasma in sinus augmentation: a critical review. Implant Dent 2006;15:160‐170.
    1. Nasirzade J, Kargarpour Z, Hasannia S, Strauss FJ, Gruber R. Platelet‐rich fibrin elicits an anti‐inflammatory response in macrophages in vitro. J Periodontol 2020;91:244‐252.
    1. Kargarpour Z, Nasirzade J, Panahipour L, Miron RJ, Gruber R. Liquid PRF reduces the inflammatory response and osteoclastogenesis in murine macrophages. Front Immunol 2021;12:636427.
    1. Wu SM, Chiu HC, Chin YT, et al. Effects of enamel matrix derivative on the proliferation and osteogenic differentiation of human gingival mesenchymal stem cells. Stem Cell Res Ther 2014;5:52.
    1. Schwartz Z, Carnes DL, Jr. , Pulliam R, et al. Porcine fetal enamel matrix derivative stimulates proliferation but not differentiation of pre‐osteoblastic 2T9 cells, inhibits proliferation and stimulates differentiation of osteoblast‐like MG63 cells, and increases proliferation and differentiation of normal human osteoblast NHOst cells. J Periodontol 2000;71:1287‐1296.
    1. Kirkbride KC, Townsend TA, Bruinsma MW, Barnett JV, Blobe GC. Bone morphogenetic proteins signal through the transforming growth factor‐beta type III receptor. J Biol Chem 2008;283:7628‐7637.
    1. Bartold M, Gronthos S, Haynes D, Ivanovski S. Mesenchymal stem cells and biologic factors leading to bone formation. J Clin Periodontol 2019;46(Suppl 21):12‐32.
    1. Al‐Hamed FS, Abu‐Nada L, Rodan R, et al. Differences in platelet‐rich plasma composition influence bone healing. J Clin Periodontol 2021;48:1613‐1623.
    1. Tomasi C, Donati M, Cecchinato D, Szathvary I, Corra E, Lindhe J. Effect of socket grafting with deproteinized bone mineral: An RCT on dimensional alterations after 6 months. Clin Oral Implants Res 2018;29:435‐442.
    1. Chappuis V, Engel O, Reyes M, Shahim K, Nolte LP, Buser D. Ridge alterations post‐extraction in the esthetic zone: a 3D analysis with CBCT. J Dent Res 2013;92:195S‐201S.

Source: PubMed

3
Prenumerera