Titanium Meshes in Guided Bone Regeneration: A Systematic Review

coatings Systematic Review Titanium Meshes in Guided Bone Regeneration: A Systematic Review Ricard Aceves-Argemí1, Elisabet Roca-Millan 1, Beatriz González-Navarro 1,2 , Antonio Marí-Roig 2,3 , Eugenio Velasco-Ortega 4and JoséLópez-López 2,5,*   Citation: Aceves-Argemí, R.; Roca-Millan, E.; González-Navarro, B.; Marí-Roig, A.; Velasco-Ortega, E.; López-López, J. Titanium Meshes in Guided Bone Regeneration: A Systematic Review. Coatings 2021,11, 316. https://doi.org/10.3390/ coatings11030316 Academic Editor: Jun-Beom Park Received: 21 February 2021 Accepted: 8 March 2021 Published: 10 March 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Faculty of Medicine and Health Sciences, School of Dentistry, University of Barcelona, 08907 Barcelona, Spain; [email protected] (R.A.-A.); er[email protected] (E.R.-M.); [email protected] (B.G.-N.) 2Oral Health and Masticatory System Group-IDIBELL, Faculty of Medicine and Health Sciences, School of Dentistry, Odontological Hospital University of Barcelona, University of Barcelona, 08907 Barcelona, Spain; [email protected] 3Department of Maxillofacial Surgery, University Hospital of Bellvitge, 08907 Barcelona, Spain 4Department of Stomatology, Faculty of Dentistry, University of Seville, 41013 Seville, Spain; [email protected] 5Department of Odontostomatology, Faculty of Medicine and Health Sciences (Dentistry), Odontological Hospital University of Barcelona, University of Barcelona, 08907 Barcelona, Spain *Correspondence: [email protected] Abstract: The presence of satisfactory bone volume is fundamental for the achievement of osseointegration. This systematic review aims to analyse the use of titanium meshes in guided bone regeneration in terms of bone gain, survival and success rates of implants, and percentages of exposure. An electronic search was conducted Articles were selected from databases in MEDLINE (PubMed), SCOPUS, Scielo, and Cochrane Library databases to identify studies in which bone regeneration was performed through particulate bone and the use of titanium meshes. Twenty-one studies were included in the review. In total, 382 patients, 416 titanium meshes, and 709 implants were evaluated. The average bone gain was 4.3 mm in horizontal width and 4.11 mm in vertical height. The mesh exposure was highly prevalent (28%). The survival rate of 145 simultaneous implants was 99.5%; the survival rate of 507 delayed implants was 99%. The success rate of 105 simultaneous implants was 97%; the success rate of 285 delayed implants was 95.1%. The clinical studies currently available in the literature have shown the predictability of this technique. It has a high risk of soft tissue dehiscence and membrane exposure although the optimal management of membrane exposition permits obtaining a sufficient bone regeneration volume and prevents compromising the final treatment outcome. Keywords: titanium mesh; bone graft; guided bone regeneration; ridge augmentation 1. Introduction Satisfactory bone volume is the first condition for obtaining a predictable long-term prognosis in oral implantology. However, some patients may present inadequate bone, which frequently makes difficult the successful outcome of the correct implant placement. Different techniques have been developed to increase bone volume, but at the present time, guided bone regeneration (GBR) represents the gold standard in bone regeneration for implant placement [ 1 , 2 ]. The biological bases of this technique focus on the “PASS” principles: primary closure, angiogenesis, space maintenance, and blood clot stability [ 3 ], in other words, this technique focus on the mechanical protection of the blood clot and the isolating of the bone defect, by using a barrier, to facilitate the migration and proliferation of bone-forming cells and to prevent soft tissue colonization inside the bone defect [ 1 , 4 ]. In the last two decades, several membrane designs have been studied. They can be divided into two categories: absorbable and non-resorbable, with different physical and biomaterial properties between them, but all types must have some properties such as Coatings 2021,11, 316. https://doi.org/10.3390/coatings11030316 https://www.mdpi.com/journal/coatings Coatings 2021,11, 316 2 of 13 biocompatibility, tissue integration, space-making, cell selectivity, tissue integration, and clinical manageability [ 5 , 6 ]. The physical and biomaterial properties of the membranes will influence the development of their function, as well as the result of the treatment, therefore, it will be of great importance to know the advantages and disadvantages of each of them [5,6]. The non-resorbable barriers are expanded and dense forms of titanium-reinforced polytetrafluoroethylene membranes (e-PTFE and d-PTFE), the titanium foils, and perforated titanium meshes (preshaped or customized) (Figure 1). Coatings 2021, 11, x FOR PEER REVIEW 2 of 14 biomaterial properties between them, but all types must have some properties such as biocompatibility, tissue integration, space-making, cell selectivity, tissue integration, and clinical manageability [5,6]. The physical and biomaterial properties of the membranes will influence the development of their function, as well as the result of the treatment, therefore, it will be of great importance to know the advantages and disadvantages of each of them [5,6]. The non-resorbable barriers are expanded and dense forms of titanium-reinforced polytetrafluoroethylene membranes (e-PTFE and d-PTFE), the titanium foils, and perforated titanium meshes (preshaped or customized) (Figure 1). (a) (b) Figure 1. (a) Custom-made titanium mesh (AVINENT ®® Digital Health); (b) Use of Computer-Aided Design (CAD) and Computer-Aided manufacturing (CAM)to design custom-made devices for guided bone regeneration (GBR). The biggest disadvantage of these types of membranes is they need to be removed with a second-stage surgical procedure. Despite this, they offer several advantages such as, maintaining the space for a sufficient period of time, providing an effective barrier function in terms of biocompatibility, they are simple to manage and present a reduced risk of long-term complications [7]. In cases where vertical augmentation is desired, or in the presence of severe bone atrophy, the use of more resistant and stable membranes is required. To satisfy these requirements, the e-PTFE membranes were subjected to modifications such as titanium reinforcement that favoured their properties and predictability, or the use of screws in its fixation to improve stability [8]. Thus, the titanium mesh appeared to intend to obtain a balance between the ideal malleability and enough rigidity to accomplish reconstructions of wide bone defects [9]. In the last 8 years, only three reviews about this subject have been conducted [10–12], therefore, the main objective was to assess the use of titanium meshes during guided bone regeneration, the quantity of augmented bone, survival and success rates of implants, complications, and predictability of this surgical technique. 2. Materials and Methods The systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) scale [13]). 2.1. Focused Questions The following focused questions were formulated: 1. Is the use of titanium mesh in combination with a particulate bone graft (autologous and/or heterologous) a successful technique regarding the quantity of augmented bone? 2. What is the percentage of membrane exposures? Figure 1. ( a ) Custom-made titanium mesh (AVINENT ®® Digital Health); ( b ) Use of Computer-Aided Design (CAD) and Computer-Aided manufacturing (CAM)to design custom-made devices for guided bone regeneration (GBR). The biggest disadvantage of these types of membranes is they need to be removed with a second-stage surgical procedure. Despite this, they offer several advantages such as, maintaining the space for a sufficient period of time, providing an effective barrier function in terms of biocompatibility, they are simple to manage and present a reduced risk of long-term complications [7]. In cases where vertical augmentation is desired, or in the presence of severe bone atrophy, the use of more resistant and stable membranes is required. To satisfy these requirements, the e-PTFE membranes were subjected to modifications such as titanium reinforcement that favoured their properties and predictability, or the use of screws in its fixation to improve stability [ 8 ]. Thus, the titanium mesh appeared to intend to obtain a balance between the ideal malleability and enough rigidity to accomplish reconstructions of wide bone defects [9]. In the last 8 years, only three reviews about this subject have been conducted [ 10 – 12 ], therefore, the main objective was to assess the use of titanium meshes during guided bone regeneration, the quantity of augmented bone, survival and success rates of implants, complications, and predictability of this surgical technique. 2. Materials and Methods The systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) scale [13]). 2.1. Focused Questions The following focused questions were formulated: 1. Is the use of titanium mesh in combination with a particulate bone graft (autologous and/or heterologous) a successful technique regarding the quantity of augmented bone? 2. What is the percentage of membrane exposures? 3. What are the implant survival, success, and failure rate when performing this bone regeneration technique in simultaneous or delayed implant placement? Coatings 2021,11, 316 3 of 13 2.2. PICO Question Bulleted lists look like this: •P: Patients with partially o total edentulism candidates for GBR. • I: Bone regeneration through autologous and/or heterologous bone graft and the use of titanium meshes. •C: Different grafting materials and techniques. • O: The success rate of this technique regarding the quantity of augmented bone, complications, and predictability of this surgical technique. 2.3. Eligibility Criteria Inclusion criteria: (i) Studies in which a bone regeneration was performed using particulate bone graft (autologous and/or heterologous) and the use of titanium meshes; (ii) Clinical trials, cohort studies, and case series; (iii) Published in English or Spanish; (iv) Minimum 6 months follow-up period. Exclusion criteria: (i) Studies performed in vitro or on animals; (ii) Systematic reviews, case reports, and expert opinions; (iii) Studies published before January 2000. 2.4. Information Sources An electronic search was conducted in MEDLINE (PubMed), SCOPUS, Scielo, and Cochrane Library databases for articles published between 2000 and 2021. References of relevant studies selected were also searched to identify articles with potential inclusion. The last search was performed on 8th January 2021. 2.5. Search Strategy The following search terms were used: 1. (Titanium mesh [All Fields] AND bone graft [All Fields]). 2. ((Titanium mesh [All Fields] AND (guided bone regeneration [All Fields] OR GBR [All Fields])). 3. (Titanium mesh [All Fields] AND ridge augmentation [All Fields]). 2.6. Study Selection All articles were reviewed initially by three experts (R.A.-A., E.R.-M., and B.G.-N.). In the event of any discrepancies, these were resolved by J.L.-L. The first phase of the research consisted of the selection of titles, to eliminate those not concerning our research and eliminate the repeated ones. The second phase consisted of reading the abstract of each article to evaluate some parameters of inclusion. Finally, the full text of all studies selected was obtained. 2.7. Data Collection Process and Items One reviewer R.A.-A., extracted the data from the selected studies, including characteristics of the study (authors, year of publication, country, and design), sample characteristics (number of patients, mean ages, and number of sites), surgery characteristics (the type of defect, type of surgery performed and materials used) and finally, the post-operatory details and outcomes (follow-up period, percentage of membrane exposures, horizontal/vertical bone regeneration obtained and implant survival, success, and failure rate) which were synthesized in Table 1and Table 5. A second author (B.G.-N.) verified all the information collected. The implant success rate was evaluated according to Albrektsson et al. criteria [ 14 ]: (i) Absence of subjective complaints such as pain, foreign body sensation, and/or dysesthesia; (ii) Absence of mobility; (iii) Absence of peri-implant radiolucency and infection with pus suppuration; (iv) Marginal bone resorption (MBR) not exceeding 1.5 mm after the first year of loading and up to 0.2 mm yearly thereafter. Coatings 2021,11, 316 4 of 13 2.8. Risk of Bias in Individual Studies The methodology of the included randomized clinical trials (RCT) was evaluated using the Cochrane Collaboration’s risk of bias (RoB 2) tool [ 15 ]. The risk of bias for the non-randomized clinical trials (NRCT), was determined using the non-randomized clinical trials of Interventions (ROBINS-I) assessment tool [ 16 ]. The risk of bias was classified as “low risk”, “unclear risk”, and “high risk”. Table 1. Characteristics of the included studies. Author/Country Type of Study “N” Mean Ages Number of Sites Type of Defects Graft Materials Second- Stage Surgery (m) Mesh Exposure (%) Bone Augmentation (mm) M F (y) Mx Md MHA MVA Miyamoto et al., 2001/Japan [17]Case series 16 25 46 29 21 C, V, S Autologous 6 36 4 8,9 Degidi et al., 2003/Italy [18]Case series 4 14 47.5 - - - Autologous 4Md 0- - 6Mx Proussaefs et al., 2006/USA [19]Case series 10 7 50.6 17 C Autologous + ABB 50:50 8.47 35.3 3.75 2.56 Pinho et al., 2006/Brazil [20]RCT 10 46.3 10 -V, H Test: Autologous 6 50 8.4 11.4 1 10 Control: None 8.8 11.4 1 Corinaldesi et al., 2007/Italy [21]NRCT 3 3 49.3 3 3 C Test: Autologous + BPBM 70:30 8−9-- 4 4 2 57.7 3 3 Control: Autologous - 4.16 Pieri et al., 2008/Italy [22] Prospective study 7 9 49.6 9 10 C Autologous + ABB 70:30 8−9 5.3 4.16 3.71 Corinaldesi et al., 2009/Italy [23]Case series 9 15 48.4 27 C Autologous 8−9 14.8 - 4.9 Torres et al., 2010/Spain [24]RCT 7 9 -27 16 V, H, C Test: ABB + PRP 60 3.4 4.1 6 8 Control: ABB 28.5 3.1 3.7 Her et al., 2012/South Korea [25] Case series 11 15 51 9 18 C, H Autologous + ABB Alloplastic Autologous+Alloplastic 5.7 26 - - Lizio et al., 2014/Italy [26]Case series 2 10 49.1 11 4 C, V Autologous + ABB 70:30 8−9 80 - - Poli et al., 2014/Italy [27]Case series 8 5 - 11 2 C Autologous + DBBM 50:50 6 7.68 - - Sumida et al., 2014/Japan [28]NRCT 3 10 47 - - - Autologous + CD 623.1 - - 4 9 48 Autologous + CMD 7.7 - - Uehara et al., 2015/Germany [29] Case series 7 14 47.5 11 12 C, V, S Autologous + Hydroxyapatite 50:50 3−7 70 - - Zita et al., 2016/ Portugal [30]Case series 15 10 54.3 - - H ABB 3−4 24 3.67 - Bassi et al., 2016/Italy [31]Case series 1 9 58 0 10 C, H, V TMAP 6.7 30 8.6 6.1 Ciocca et al., 2018/Italy [32] Prospective study 3 6 50.2 6 5 V Autologous + ABB 50:50 6−8 66.6 - 3.8 Md 3.9 Mx Cucchi et al., 2019/Italy [33]RCT 20 52 - - V Autologous + Allograft 50:50 9 21.1 - 4.1 Zhang et al., 2019/China [34]Case series 12 - 16 0 C ABB 4−8 6.25 3.1 3.61 Atef et al., 2020/Egypt [35]RCT 10 - - - H Autologous + ABB 50:50 6 40 3.7 - Coatings 2021,11, 316 5 of 13 Table 1. Cont. Author/Country Type of Study “N” Mean Ages Number of Sites Type of Defects Graft Materials Second- Stage Surgery (m) Mesh Exposure (%) Bone Augmentation (mm) M F (y) Mx Md MHA MVA Malik et al., 2020/India [36]Case series 12 8 48.7 0 20 V TMAP 6 20 - 4.82 Cucchi et al., 2020/Italy [37]Case series 5 5 52 5 5 V Autologous + ABB 50:50 6−9 10 - 4.5 Mx: Maxilla; Md: Mandible; MHA: Mean horizontal augmentation; MVA: Mean vertical augmentation C: Combined; H: Horizontal; V: Vertical; S: Socket; DBBM: Demineralized bovine bone mineral; ABB: Inorganic bovine bone; BPBM: Bovine porous bone protein; TMAP: Thermoplastic mouldable allograft paste. RCT: Randomized clinical trial; NRCT: Non-randomized clinical trial. 1 : Referred to vertical and horizontal bone fill of sockets after tooth extraction; CD: Conventional device; CMD: Custom made device. 3. Results 3.1. Study Selection A total of 572 articles were identified in the first phase of the research. During the second phase, 94 articles were considered, and after full-text evaluation 16 studies were included in the review. Finally, five articles of interest were obtained through manual research obtaining a total of 21 articles were included in this review [17–37] (Figure 2). Coatings 2021, 11, x FOR PEER REVIEW 5 of 14 Zita et al. 2016/Portugal [30] Case series 15 10 54.3 - - H ABB 3−4 24 3.67 - Bassi et al. 2016/Italy [31] Case series 1 9 58 0 10 C, H, V TMAP 6.7 30 8.6 6.1 Ciocca et al. 2018/Italy [32] Prospective study 3 6 50.2 6 5 V Autologous + ABB 50:50 6−8 66.6 - 3.8 Md 3.9 Mx Cucchi et al. 2019/Italy [33] RCT 20 52 - - V Autologous + Allograft 50:50 9 21.1 - 4.1 Zhang et al. 2019/China [34] Case series 12 - 16 0 C ABB 4−8 6.25 3.1 3.61 Atef et al. 2020/Egypt [35] RCT 10 - - - H Autologous + ABB 50:50 6 40 3.7 - Malik et al. 2020/India [36] Case series 12 8 48.7 0 20 V TMAP 6 20 - 4.82 Cucchi et al. 2020/Italy [37] Case series 5 5 52 5 5 V Autologous + ABB 50:50 6−9 10 - 4.5 Mx: Maxilla; Md: Mandible; MHA: Mean horizontal augmentation; MVA: Mean vertical augmentation C: Combined; H: Horizontal; V: Vertical; S: Socket; DBBM: Demineralized bovine bone mineral; ABB: Inorganic bovine bone; BPBM: Bovine porous bone protein; TMAP: Thermoplastic mouldable allograft paste. RCT: Randomized clinical trial; NRCT: Non-randomized clinical trial.1: Referred to vertical and horizontal bone fill of sockets after tooth extraction; CD: Conventional device; CMD: Custom made device. 3. Results 3.1. Study Selection A total of 572 articles were identified in the first phase of the research. During the second phase, 94 articles were considered, and after full-text evaluation 16 studies were included in the review. Finally, five articles of interest were obtained through manual research obtaining a total of 21 articles were included in this review [17–37] (Figure 2). Figure 2. Flow diagram of study inclusion. Figure 2. Flow diagram of study inclusion. 3.2. Study Methods and Characteristics Four studies were RCT [ 20 , 24 , 33 , 35 ], 2 were NRCT [ 21 , 28 ], 2 were prospective studies [ 22 , 32 ] and 13 were case series [ 17 – 19 , 23 , 25 – 27 , 29 – 31 , 34 , 36 , 37 ] and all of them were published between 2001 and 2021 (Table 1). The studies were conducted in nine different countries, the total number of patients included was 382 (137 males, 193 females, and 52 non-specified) and a total of 416 titanium meshes. There were four articles in which the gender was not specified [ 20 , 33 – 35 ]. The study with a higher number of patients was Miyamoto et al. (N = 41) [ 17 ] while the one with fewer patients was Ciocca et al. [ 29 ] with a total of nine patients. The mean age was 53.4 and four articles did not specify the mean age [24,27,34,35]. Coatings 2021,11, 316 6 of 13 Regarding the characteristics of the surgeries performed, it was quantified the number of sites, and whether if it was in mandible or maxilla. In five studies, the number of sites was not specified [18,28,30,34,35], of which 164 sites belong to the maxilla and 129 to the mandible. In 16 studies the graft material used was autologous bone; in six of them it was the only material used [ 17 , 18 , 20 , 21 , 23 , 28 ] (N = 120), and in the other 10 articles, autologous bone was associated with other graft materials such as inorganic bovine bone (ABB) [19,22,25,26,32,35,37] (N = 91), thermoplastic mouldable allograft paste (TMAP) [ 33 ] (N = 28), bovine porous bone protein (BPBM) [ 21 ] (N = 3), demineralized bovine bone mineral (DBBM) [ 27 ] (N = 13) or Hydroxyapatite [ 29 ] (N = 21). There were five studies in which autologous bone was not used and the regeneration was performed only with the use of ABB [24,30,34] (N = 67) or TMAP (36,31) (N = 39). The removal of the mesh and the quantification of bone gains was performed during the second-stage surgery or also called in most studies as healing period, which was performed on average at 6.5 months. 3.3. Quality Assessment and Risk of Bias within Studies The risk of bias of the RCT is presented in Table 2. Three RTCs were considered as having a low risk of bias even though there were some concerns about the blinding of participants and researchers [ 24 , 33 , 35 ] and Atef et al. did not report the blinding of outcome assessment and selective outcome reporting, potentially introducing selection bias [ 35 ]. One study was considered as having a high risk of bias since there were some concerns about the random sequence generation, the allocation concealment, and the blinding of participants and researchers [20]. Table 2. Risk of Bias of included randomized clinical trials. Author Random Sequence Generation Allocation Concealment Blinding of Participants and Researchers Blinding of Outcome Assessment Incomplete Outcome Data Selective Outcome Reporting Other Sources of Bias Pinho et al., 2006 [20]? ? ? L L ? L Torres et al., 2010 [21–24]L L ? L L L L Cucchi et al., 2019 [33]L L ? L L L L Atef et al., 2020 [35]L L ? ? L ? L L: Low; (?): Unclear; H: High. Two non-randomized clinical trials were included, and the risk of bias is represented in Table 3. These two articles were considered as having a low risk of bias but there were some concerns about potential bias in the classification of interventions [ 21 , 28 ] and also due to deviations from intended interventions [21]. Table 3. Risk of Bias of included non-randomized clinical trials. Author Bias Due to Confounding Bias in Selection of Participants into the Study Bias in Classification of Interventions Bias due to Deviations from Intended Interventions Bias due to Missing data Bias in Measurement of Outcomes Overall Bias Corinaldesi et al., 2007 [21]L L ? ? L L L Sumida et al., 2015 [28]L L ? L L L L L: Low; (?): Unclear; H: High. Coatings 2021,11, 316 7 of 13 (The systematic review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) scale [13]) with 21 items. 3.4. Characteristics of the Mesh Different types of meshes were used in the studies, all of them are summarized in Table 4. Table 4. Characteristics of the meshes used. Authors Characteristics of the Mesh Used Thickness Miyamoto et al., 2001 [17]Preshaped titanium mesh (M-TAM, Stryker Leinger GmbH & Co., KG, Freiburg ASTM F-67 Jeil Medical Corp., Seoul, Korea) 0.1 and 0.2 mm thick Degidi et al., 2003 [18] Preshaped micromesh (Cortical Mesh, Micronova, Bologna, Italy) NE Proussaefs et al., 2006 [19] Preshaped titanium mesh (Osteo-Tram; OsteoMed) 0.2 mm thick Pinho et al., 2006 [20] Preshaped titanium mesh (Frios Boneshield; DENTSPLY Friadent) NE Corinaldesi et al., 2007 [21] Preshaped and trimmed titanium micromesh (ACE surgical supply, Straumann) 0.2 mm thick Pieri et al., 2008 [22]Preshaped titanium mesh (Modus 1.5 Mesh, Straumann, Waldenburg, Switzerland) NE Corinaldesi et al., 2009 [23]Preshaped and trimmed titanium mesh (ACE Titanium Micro Mesh, ACE Surgical Supply Company; Modus 0.9 Mesh, Medartis) 0.2 mm thick Torres et al., 2010 [24] Preshaped and trimmed titanium mesh NE Her et al., 2012 [25]Preshaped and trimmed titanium mesh (Jeil Medical, Seoul, South Korea) 0.1 mm thick Lizio et al., 2014 [26] Titanium mesh (ridge-form; OsteoMed) 0.2 mm thick Poli et al., 2014 [27]Preshaped and trimmed titanium mesh (ridge-form; (KLS Martin, Tuttlingen, Germany) 0.2 mm thick Sumida et al., 2014 [28]Custom-made titanium mesh (Ace Surgical SupplyCo., Inc. Brockton, MA, USA) 0.5 mm thick Uehara et al., 2015 [29]Preshaped and trimmed microtitanium mesh (Striker-Leibinger, Freiburg, Germany) 0.1 mm thick Zita et al., 2016 [30] Titanium mesh (i–Gen, MegaGen, Gyeongbuk, Republic of Korea) NE Bassi et al., 2016 [31] Titanium foil (grade 4) 0.2 mm thick Ciocca et al., 2018 [32]Custom-made titanium mesh (Electro Optical Systems, Munich, Germany) 0.1 mm Cucchi et al., 2019 [33] Preshaped titaium mesh (Trinon Titanium; Karlsruhe, Germany) NE Zhang et al., 2019 [34] L-Shaped titanium mesh; Preshaped and trimmed 0.2 mm thick Atef et al., 2020 [35] Preshaped titanium mesh (Bioinnovation, Brazil) NE Malik et al., 2020 [36] Preshaped and trimmed titanium mesh NE Cucchi et al., 2020 [37]Custom-made titanium mesh (3D-Mesh®®, Biotec Srl, Dueville, Vicenza, Italy) >0.5 mm thick NE: Not evaluated. 3.5. Bone Gain The bone gains were quantified using cone-beam computed tomography (CBCT) images. In two studies, width bone gain was quantified [ 30 , 35 ], five studies quantified height bone gain [ 21 , 23 , 33 , 36 , 37 ], six studied both width and height bone gains [17,22,24,29,31,34] and finally 5 works did not quantify any bone gains after the surgery [ 18 , 22 , 26 , 27 , 29 ]. The average bone gains were 4.3 mm in horizontal width (range 3.1 mm performed with ABB to 8.6 mm performed with TMAP) and 4.11 mm in vertical height (range 2.56 mm performed with autologous and ABB 50:50 to 8.9 mm performed only with autologous). Coatings 2021,11, 316 8 of 13 One study performed GBR after tooth removal, to evaluate the prevention of alveolar collapse after tooth extraction, using titanium membrane [20]. Four studies evaluated the histologic and histomorphometric outcomes of GBR from biopsies of the newly regenerated bone [ 19 , 21 , 31 , 33 ]. According to Bassi et al. [ 31 ], the histological and histomorphometric analysis of the samples demonstrates the effectiveness of GBR employing titanium mesh, as a barrier membrane. Cucchi et al. [ 33 ] concluded that the regenerated bone differed from the native bone in terms of trabecular organization, as well as newly formed bone remained immature and very different from the native bone. Proussaefs et al. [ 19 ] demonstrated 36.47% of bone formation when the titanium mesh was used in combination with autogenous bone and ABB. Corinaldesi et al. [ 21 ] concluded that BPBM (30%) in combination with the autologous bone (70%) yielded similar bone formation patterns as autologous bone alone. 3.6. Mesh Exposure Except for Corinaldesi et al. [ 21 ] all the included studies evaluated the mesh exposure (N = 404), and it proved to be a highly prevalent complication, appearing in 115 cases out of 404 meshes (28%) (range 0% to 80%). Of these 115 exposed meshes, 25 were removed due to more severe complications, and 75 were stabilized and controlled through local hygiene measures. According to the studies in which the implant was placed simultaneously [ 18 , 23 , 30 , 33 , 34 ] the mesh exposure rate was 14% (13 out of 87). In contrast, in the cases of guide bone regeneration (GBR) and delayed implant placement [ 17 , 19 , 21 – 25 , 27 , 29 , 31 , 32 , 37 ] the mean mesh exposure rate was 30% (58 out of 187). 3.7. Implant Placement Apart from performing the alveolar ridge augmentation, there were 16 studies in which dental implants were placed [ 18 , 19 , 21 – 25 , 27 , 29 – 34 , 37 ] (Table 4). The other five studies focused on the bone regeneration process without involving implant placement. The outcomes were studied and summarized in Table 5. In total, 709 implants were placed and the total prevalence of implant failure in this review was 0.5% (4 implants were lost). The follow-up time after the implant placement was on average of 32 months (range 6 to 96). In five studies, bone augmentation was performed simultaneously with implant placement (N = 145) [ 18 , 23 , 30 , 33 , 34 ], in the other studies, the implant placement was delayed after 7,1 months on average (N = 564) (range 3 to 10 months) [17,19,21–25,27,29,31,32,37]. The implant success rate was assessed considering at least 6 months from the prosthetic load. The survival rate of 145 simultaneous implants was 99.5%; the survival rate of 507 delayed implants was 99%. The success rate of 105 simultaneous implants was 97%; the success rate of 285 delayed implants was 95.1%. Proussaefs et al. [ 19 ] did not specify the survival and success rates and Corinaldesi et al. [ 21 ], Torres et al. [ 24 ], Zita et al. [ 30 ], and Ciocca et al. [32] did not specify the success rate. The marginal bone resorption (MBR) was evaluated in 6 studies and it was on average of 0.75 mm [ 19 , 22 – 24 , 30 , 31 , 37 ] (N = 234). There were no statistically significant differences between de MBR observed in the simultaneous implants and delayed implants. Coatings 2021,11, 316 9 of 13 Table 5. Evaluation of characteristics of implant placement. Author/Country Implant Placement Implants Implant Lost Bone Loss (mm) Success Rate (%) Survival Rate (%) Follow-up (m) Mx Md Miyamoto et al., 2001/Japan [17] After 6 months 89 1 - 94 92.8 47.5 Degidi et al., 2003/Italy [18] Simultaneously 50 0 - 100 100 84 Proussaefs et al., 2006/USA [19]After 9−10 months 36 5 - 0 MBR - - 6 Corinaldesi et al., 2007/Italy [21] After 8−9 months 20 15 0 - - 100 12 Pieri et al., 2008/Italy [22] After 8−9 months 21 23 0 1.36 MBR 93.2 100 12 Corinaldesi et al., 2009/Italy [23]Simultaneously After 8−9 months 20 36 0 0 1.22 MBR 1.26 MBR 96.4 100 36−96 Torres et al., 2010/Spain [24] After 6 months 97 3 - - 98.6 24 Her et al., 2012/South Korea [25] After 5−7 months 27 41 0 - 100 100 6−24 Poli et al., 2014/Italy [27] After 6 months 16 4 0 1.74 M, 1.91 D 100 100 88 Uehara et al., 2015/Germany [29] After 6 months 64 1 - - 98.4 40 Zita et al., 2016/Portugal [30] Simultaneously 32 8 1 0.43 MBR - 97.5 12 Bassi et al., 2016/Italy [31] After 6−7 months 0 18 0 1.17 MBR 88.2 100 12 Ciocca et al., 2018/Italy [32] After 6−8 months 14 12 0 - - 100 24 Cucchi et al., 2019/Italy [33] Simultaneously 0 19 0 0 MBR 100 100 12 Zhang et al., 2019/China [34] Simultaneously 16 0 0 0.81 V 0.13 H 93.75 100 24 Cucchi et al., 2020/Italy [37] After 6−9 months 14 12 0 0 MBR 100 100 12 M: Mesial; D: Distal; MBR: Marginal bone resorption; V: Vertical; H: Horizontal. 4. Discussion From the analysis of the recent published articles, few studies concerning GBR using titanium mesh were published. The present systematic review aimed to evaluate the results reported in the literature evaluating the following aspects: (a) the success rate of this technique regarding the quantity of augmented bone; (b) the complications rate by means of exposure; (c) the implants survival and success rate. The topic was focused on the presence of the titanium meshes used as a physical barrier for ridge reconstruction in partial or total edentulism, preventing soft tissue colonization and allowing osteoprogenitor cells to reach the site and form new bone. 4.1. Bone Gain The use of non-resorbable titanium meshes allows maintaining the shape between the barrier and the bone defect. Furthermore, the pores allow to maintain vascularization both to the soft tissue and to the bone during the regeneration process and facilitates tissue nutrition [ 12 , 38 ]. Generally, the literature showed that the use of non-resorbable titanium meshes in GBR represent a safe and predictable technique to gain vertical and/or horizontal bone augmentation, in the treatment of small and medium-sized defects around dental implants and prevention of alveolar ridge after tooth extraction [ 9 , 20 , 30 , 35 ]. The analysis of the studies included in the present systematic review corroborates this statement, although only six included studies quantified both width and height bone gains [ 17 , 19 , 22 , 24 , 31 , 34 ]. The histological and histomorphometric analysis also demonstrates the effectiveness of GBR using the titanium mesh, and good capacity of the method to increase bone volume in the distal mandibular atrophies [ 19 , 21 , 31 , 33 ]. On the other hand, other authors like Uehara et al. [ 29 ] appear more doubtful about the success of this technique. According to their success criteria, only 13 sites were judged as successful with a success rate of 56.6%, emphasizing that, the greatest success rate was obtained at the sites with a shorter span of augmentation.