Effect of Exposure Rates With Customized Versus Conventional Titanium Mesh on Guided Bone Regeneration: Systematic Review and Meta-Analysis

The quality and quantity of the alveolar ridge is the key to the successful implantation and long-term stability of implants.¹  Based on reabsorption, alveolar ridge defects can be divided into horizontal, vertical, and combined complex defects.²  Horizontal-vertical bone defects have been considered to be the most difficult type to augment.³ 

Guided bone regeneration (GBR) is the gold standard for implant bone regeneration.^4,5  The success of GBR requires 4 main principles: initial closure, generation of blood vessels, maintenance of space, and implant stabilization.⁶ 

Some surgical augmentation methods are often used to address horizontal-vertical combined bone defects. Onlay bone augmentation and shell technology have high clinical complications and technical sensitivity.⁷  Titanium mesh combined with granular grafts is widely used in GBR of the alveolar ridge of the maxilla and mandible.^3,8,9  Autogenous bone and allogeneic bone mixed 1:1 or 1:2 have better osteogenic effects.^10,11  The titanium mesh has enough stiffness to maintain the form of the bone defect and maintain the space between the membrane and the defect. It has been widely used for all types of GBR defects.¹² 

Conventional titanium mesh needs to be pruned and bent in advance or during the operation according to individual defects or models. In some cases, the problems of constructing the ideal shape lead to increased operation time and an increased risk of infection due to mucosal rupture.¹³  Three-dimensional (3D) printing of customized titanium mesh collects data through cone beam computed tomography scanning, uses computer-aided design software to create more accurate and personalized titanium mesh for each patient to better fit the alveolar ridge, and prints molding directly to avoid the sharp edge formed by trimming. Its edge is round and blunt, which reduces the stimulation of mucosa and shortens the operation time.¹⁴ 

To date, no meta-analysis has focused on the impact of customized and conventional titanium mesh exposure rates. Therefore, the aim of this review is to ascertain the influence of the exposure rates of customized and conventional titanium mesh and the time point at which exposure occurred.

This systematic review follows the structural pattern in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The methods used in this systematic review were registered in the PROSPERO database (CRD42020175788).

The main question was as follows: Does GBR for ridge augmentation with customized titanium mesh have complication rates similar to those with conventional titanium mesh?

PICOS (Population, Intervention, Comparison, Outcome, Study)

• P:

  Healthy subjects with alveolar ridge atrophy and complete or partial edentulous jaws that required implant surgery to restore oral function.

• I:

  Use of titanium mesh in GBR for vertical and/or horizontal ridge augmentation for implant placement.

• C:

  Conventional titanium mesh vs customized titanium mesh with particulate bone graft (xenogeneic, allogeneic, and/or autogenous graft).

• O:

  (Primary outcome)—the exposure rate of customized titanium mesh is lower than that of conventional titanium mesh; (Secondary outcome)—mesh exposure time.

• S:

  Randomized clinical trials (RCTs), prospective studies (PSs), retrospective studies (RTSs), and clinical studies (CSs).

Two independent reviewers used 4 databases, including PubMed, EMBASE, Web of Science, and Cochrane Central Register Controlled Trials, to conduct electronic literature retrieval. Articles whose language was limited to English from January 2010 to March 2020 were included. When the first 2 authors had conflicting views, a third author who performed a careful analysis was consulted, and consensus was reached through discussion.

For the PubMed database, combinations of controlled terms ([mh] represents MeSH terms) and keywords ([all] represents full-text search) were used whenever possible. As such, the key terms used were (“guided bone regeneration”[all] OR “GBR”[all] OR “alveolar ridge augmentation”[mh]) AND “titanium”[all].

For the other databases, the key terms used were guided bone regeneration, alveolar ridge augmentation, and titanium.

Screening of these databases was confined to “clinical trial” AND “humans”.

• Studies conducted only in humans, including randomized and nonrandomized clinical trials, cohort studies, and case series, were included.

• Articles on regeneration through particulate bone (autogenous bone or a mixture of autogenous and xenogeneic bone) were included. It is shown that PRF has no effect on the results and can be included in this article.

• Articles including the use of customized titanium mesh or conventional titanium mesh were included.

• The shortest follow-up time was 6 months.

• The defects after treatment included the characteristic of no space.

• In vitro studies, animal studies, clinical cases, and literature reviews were excluded.

• No case reports were included. In addition, studies with fewer than 8 study sites were excluded.

• Patients with previous major systemic diseases (such as tumors or congenital malformations) were excluded. In addition, studies with concomitant interventions (eg, simultaneous elevation of the sinus floor) were excluded.

Data were extracted independently from the selected articles. The data from each study recorded included the type of study design, number of participants, bone graft materials used, selection of mesh type, operation method, initial bone width and height, incidence of mesh exposure, time of complications, success rate of transplantation, and follow-up time after regeneration surgery.

Statistical software R version 4.0 was used in this meta-analysis (package “meta” version 4.11-0). The analysis method was “meta-analytical,” and the inverse variance method (inverse variance method for random effect model calculation) was used to merge the statistics. DerSimonian-Laird was used to estimate tau^2 (DerSimonian-Laird estimator was used to calculate the combined value of the random effect model), Jackson method was used to estimate the confidence interval of tau^2 and tau, and data were transformed by Arcsine transformation. The I²  test was used for the heterogeneity test, and bias analysis was conducted using funnel plots, Egger test, and the Begg method. The combined effect size in this paper is the exposure rate.

In the first stage of the screening process, we retrieved 705 potentially relevant articles from electronic databases and manual searches. We did not retrieve any articles from the open database search. A total of 575 articles were recorded after duplicates were removed. A total of 515 articles were excluded after reviewing the title/abstract, and 60 were selected for full-text assessment and included in the qualitative evaluation. After assessing the full text, 57 articles were excluded, including 3 case reports, 7 nontitanium mesh, 2 not English, 10 no data, 2 abstracts, 7 no full text, 3 reviews, and 7 not clinical. At last, 9 studies were included in the meta-analysis (Figure 1).

The selected articles were as follows: 1 CS,¹⁵  6 RTSs,^10,16–20  1 PS,²¹  and 1 RCT.²²  The included studies reported an age range of 17–88 years. A total of 218 patients were included, with slightly more female patients than male patients (156 and 62, respectively). There were a total of 247 titanium meshes, including 99 customized titanium meshes and 148 conventional titanium meshes. In addition, studies reported the treatment time range of titanium mesh (4–11 months) and the follow-up time after implant implantation (6–48 months). All studies excluded patients with systemic contraindications to oral surgery; 3 studies excluded patients with uncontrolled diabetes and pregnancy; 2 studies excluded patients with a history of head and neck radiotherapy, current antitumor therapy, liver, blood or kidney diseases, treatment with corticosteroid immunosuppressants, oral inflammation, autoimmune disease, poor oral hygiene and a lack of motivation; and 1 study excluded patients with mental illness. Seven studies reported the selection criterion of smoking. Among them, 3 studies required patients to smoke fewer than 10 cigarettes per day,^10,16,21  2 studies required patients to smoke fewer than 20 cigarettes per day,^19,20  and 2 studies showed that there were 5 and 6 smokers (Table).^17,18 

Three studies used customized titanium mesh,^17,18,21  5 studies used conventional titanium mesh,^{10,15,16,19,20}  and 1 study used both customized and conventional titanium mesh.²²  The most commonly used thicknesses of titanium mesh were 0.1 mm,^19,21,22  0.2 mm,^3,15  and 0.3 mm.²²  A total of 494 implants were implanted. Success rates for implants in several studies were 82.90%¹⁵  and 77%,¹⁰  and other studies reported implant success rates of 100%.^16–22 

The most common complication after implantation was exposure to titanium mesh, and there were 107 cases of titanium mesh exposure in the selected studies. In addition, the complications also included infection and bone resorption. Two studies reported titanium mesh exposure for 2–4 weeks,^19,21,23  in which 1 patient with obvious purulent exudation needed to have the titanium mesh removed before 3 months, and treatment for other cases of exposure did not require the removal of the mesh. Six studies reported early exposure before 4–6 weeks,^10,15,16,19  in which 4 cases of superimposed infection with the graft needed removal of the titanium mesh, and delayed exposure after 4–6 weeks,^{10,15–17,19,21}  did not require removal of the mesh after local scraping and washing with chlorhexidine. Lizio et al¹⁶  reported a positive correlation between the volume of bone defects and the exposed area.

In studies of bone increments using customized titanium mesh, Sagheb et al¹⁷  obtained that the mean vertical augmentation was 6.5 mm, and the mean horizontal augmentation was 5.5 mm. El Chaar et al²⁰  obtained that the mean vertical augmentation of conventional titanium mesh was 5.91–6.91 mm, and the mean horizontal augmentation was 5.76–6.99 mm. Two studies reported marginal bone loss, and the mean marginal bone loss was 0.6 mm¹⁵ and 1.7 ± 0.7 mm.¹⁰ 

As shown in the forest plot (Figure 2), the heterogeneity test results overall (I² = 77%, P < .01) and for the customized titanium mesh subgroup (I² = 69%, P = .02) and conventional titanium mesh subgroup (I² = 80%, P < .01) showed that the I²  were all above 50%, which suggests that there was heterogeneity among the studies. A random effects model was used to combine the statistics, and the results showed that the combined weighted exposure rate of customized titanium mesh and conventional titanium mesh was 0.44 (44%, 95% CI = 0.30∼0.58). The results in the subgroups showed that the combined exposure rate of customized titanium mesh was 0.31 (31%, 95% CI = 0.15∼0.51) and that of noncustomized titanium mesh was 0.51 (51%, 95% CI = 0.33∼0.69).

From the funnel plot in Figure 3, the Egger test results in Figure 4 (t = 0.26596, P value t = 0.797) and the test results of the Begg rank correlation method (0.17961, P value t = 0.8575), the symmetry of the funnel plot was good, and all of them were greater than 0.05. There was no obvious bias in this study.

From the analysis of the literature, few studies comparing the exposure of customized titanium mesh with that of conventional titanium mesh have been published; above all, no systematic reviews or meta-analyses have been found. Therefore, the purpose of this systematic review is to standardize the results reported in the literature. According to the results of the present meta-analysis, customized titanium mesh is less exposed than conventional titanium mesh. In addition, compared with late exposure, early exposure has a negative effect on bone regeneration.

The negative effect of titanium mesh exposure on GBR depends on exposure time and infection. Compared with the late exposure at 4 weeks after operation, the osteogenesis of the early exposure site decreased significantly, and the possibility of being removed was higher; titanium mesh is usually exposed for 2–3 weeks after placement and partially osteogenic.¹⁵  However, exposure 4 weeks after the operation had little effect on the clinical effect of bone augmentation and the success rate of the implant.^15,24,25  It has been suggested that in the early stage of wound healing, the “pseudoperiosteum,” which protects the graft material from infection has not been formed.^3,12,26  The success of bone regeneration can also be achieved by timely treatment of an early exposure. The exposure site was washed with chlorhexidine and treated with antibiotics; the sharp edges and angles of the exposed mesh were removed and observed continuously. When the graft materials are infected, the titanium mesh should be removed.^15,19 

The relationship between the occurrence of exposure and the type of mesh suggests that customized titanium mesh is the preferred method for GBR. In addition, it has many clinical advantages. It avoids bending and trimming, and its edge is round and blunt, reducing exposure caused by mucosa stimulation and operation time.¹⁷  Sumida et al²²  reported that the operation time of customized mesh was reduced by approximately 30 minutes, and the number of retaining screws could be reduced to 1–2. Ciocca et al²¹  observed similar finding. In addition, using the 3D printing selective laser melting method to make titanium mesh has strong mechanical properties, and the surface is polished to make it smooth.²⁷  However, it is not without complications.

The risk of mucosal rupture and infection still needs attention. Tension-free closure of the wound and management of the soft tissue help stabilize the graft material and increase the success of bone augmentation surgery.²⁸  Altiparmak et al²⁹  found that soft tissue dehiscence and graft failure were significantly less common in patients undergoing the tunnel technique. Releasing incisions of the periosteum along the buccal flap permitted extension of the flap coronally over the mesh to provide tension-free sutures and thus avoiding tissue necrosis and premature exposure.^10,16,19,20  The edge of the wound is located in the vestibule because it is the most important survival nutrient structure and the basis for wound healing. The preparation of small round holes on the defect cortex causes hemorrhage and infiltration of osteoblasts, and it is also a nutrient hole in the marrow cavity.¹⁹  In addition, different anatomic sites also affect soft tissue dehiscence. The thin mucosa from the mandibular central incisor to the first premolar will compromise tension-free closure and soft tissue healing of the wound.^30,31 

Normal soft tissue healing can not only protect bone substitute materials in the required position but also provide blood supply and nutrition. However, there are many potential factors affecting soft tissue healing. Two studies have shown that males are at higher risk of developing soft tissue dehiscence during bone regeneration.^18,32  Dao and Kazin³³  reported the differences in skin regeneration between men and women. The drop in testosterone levels in males leads to a change in the immune process that increases the risk of ruptured wounds. Hartmann and Seiler¹⁸  demonstrated that smoking did not affect the exposure rate, which may be related to the reduction or avoidance of smoking after surgery. However, smokers are at a higher risk of losing more grafts when exposed.³⁴  Additionally, the operation skill of the clinician is also a potential factor affecting the success of the operation. The complications also showed postoperative edema, pain, or discomfort; however, they were minor in nature, as they could be easily managed with anti-inflammatory drugs, resolving during the first week.²⁴ 

Proper thickness, porosity, and shape of titanium mesh contribute to osteogenesis and reduce exposure. It was verified that 0.1 mm^19,22 and 0.2 mm^15,16 titanium mesh had good osteogenic effects. The thicker the titanium mesh is, the stronger the ability to maintain space, but the mucosa is easily stimulated by exposure. Therefore, it is very important to choose the right thickness. Studies have demonstrated that mesh with a 0.5-mm pore diameter has the most cell attachment, which is effective in guiding the early bone healing of bone regeneration.^35,36  The porosity of titanium mesh is controlled between 65% ∼ 80%, and the compressive strength and osteogenesis effect are good.^37,38  The mesh shapes used in the study are round,^19–22  square,^15,16  hexagonal,^10,20  and irregular.^17,18  It remains to be studied which pore type has a greater promoting effect on cells. The advantage of customized titanium mesh is that it can be designed to fit the thickness, aperture, and shape according to the patient's condition, improving the success rate and enhancing the effect of precise implantation.

Some scholars have shown that the exposure rate of conventional titanium mesh is as high as 28.5%–55%,³⁹  and the exposure rate of the traditional titanium mesh included in the paper was calculated to be 51%. It has been proven that exposure is a factor affecting bone regeneration. Chan et al³⁰  reported that the graft material absorption rate was 28.2% ± 20.4% after exposure.

To optimize the success rate of the operation and provide sufficient alveolar bone for the implant: (i) the minimum distance from the periodontium of the neighboring teeth was 1.5 mm to prevent possible infiltrations through the gingival sulcus⁴⁰  and (ii) cover membranes with concentrated growth factors to promote soft tissue healing.

There are some limitations to be considered in this study. Of the 9 articles reviewed systematically, only 1 was an RCT, and most of the articles were CSs or RTSs. Other factors, such as different study designs, types of bone substitute materials, and clinical literature, were not adjusted uniformly in the included studies. The focus of future clinical research is still on reducing the occurrence of soft tissue complications.

Based on the findings of the present study, the exposure rate of customized titanium mesh is lower than that of conventional titanium mesh, which has more advantages in the treatment of complex bone defects. The design of 3D printing customized titanium mesh (i) avoids nerves and blood vessels, which is of great significance to improve the reconstruction accuracy of GBR, (ii) provides enough space for implantation, (iii) reduces the exposure rate, and (iv) improves surgical success rates. Soft tissue management (ie, technique sensitivity) is also an important factor to avoid the dehiscence of soft tissue. Experienced clinicians can help better manage and avoid the risk of complications.

The current findings should be cautiously interpreted because there may be uncontrolled confounding factors in the included studies. Further studies (preferably RCTs) with longer follow-up periods are recommended to determine their likely effects.

Abbreviations

3D:

three-dimensional

CS:

clinical study

GBR:

guided bone regeneration

PS:

prospective study

RCT:

randomized clinical trial

RTS:

retrospective study

This project is supported by University Nursing Program for Young Scholars with Creative Talents in Jiamusi University (Project Number: JMSUQP2020020) and University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Project Number: UNPYSCT-2020057).

The authors declare no conflicts of interest related to this study.