Large 3-dimensional defects and a reduced vertical dimension still represent challenges in bone augmentation and require a complex reconstruction.1 Guided bone regeneration (GBR) is one of the most predictable methods, well established and documented since 1968 in the field of dentistry2 even with the use of titanium implants.3 GBR uses a barrier membrane to separate the grafted defect and the surrounding connective tissue for successful bone growth.4–8 Success and survival rates of implants placed in vertically augmented bone with the GBR technique are similar to implants placed in native bone.9
When using a customized titanium mesh for GBR purposes, satisfactory bone regeneration has already been evaluated.10 This technique, based on computer-aided design/computer-aided manufacturing (CAD/CAM) technology and 3-dimensional printing, creates a patient-specific nonresorbable titanium membrane to facilitate and shorten surgery time in advance of GBR.11 Soft-tissue dehiscence and graft and membrane exposure are well-known complications associated with GBR techniques, especially with nonresorbable membranes.12–15 Mucosal rupture and flap dehiscence may be caused by failure to achieve tension-free primary wound closure or by impairment of flap microcirculation due to traumatic flap incision and elevation.14 Extensive advancement of flaps, placement of releasing incisions, and remaining high-tension forces on flaps disturb perfusion and cause ischemia. Postsurgical necrosis will cause wound dehiscence, and this premature exposure of the bone substitute reduces new bone formation and may be a risk of inflammation.13,16 Complete failure of block grafts or even neurosensory alterations may be a result. On the contrary, other authors reported that even if a titanium mesh is exposed, the incidence of inflammation is low. Therefore, premature exposure does not necessarily compromise the final treatment outcome.17–19 Sumida et al investigated custom-made titanium devices for bone augmentation compared with conventional titanium meshes. They found less exposure and consecutively better, but not statistically significant, different results for customized meshes.20
An approach to avoid wound healing difficulties and to improve bone healing is to induce vascularization of various tissues using blood-derived growth factors. Various platelet-rich preparations have been investigated to improve and accelerate wound and bone healing such as platelet-rich plasma (PRP) and platelet-rich fibrin scaffolds (PRFs).21 In terms of GBR, covering the meshes with PRP preparations helped to avoid mesh exposure.22 PRF as a second-generation platelet concentrate may also help to achieve primary wound closure over the grafted site during the augmentation process and provides multiple growth factors and cytokines. New research targets such as Injectable-Platelet-Rich Fibrin (I-PRF) has proven to release a higher level of various growth factors and to induce an intense fibroblast migration.23,24
In general, large defects of the jaws exhibit both hard- and soft-tissue shortages. Therefore, rebuilding such a complex defect with nonresorbable meshes also requires a detailed focus on soft-tissue management, and further research is needed to improve surgical outcome. So far, the literature does not provide standardized diagnostic tools for evaluating soft- and hard-tissue healing deficiencies to foresee losses of grafted material.
This study presents a new surgical protocol for advanced GBR including customized patient-specific titanium meshes, Advanced (A-) and I-PRF, resorbable membranes, and bone grafting materials for reconstruction of lateral and vertical defects of the jaw bones. The aim of the study was to evaluate potential risk factors associated with this protocol concerning soft-tissue healing according to a new classification for mesh exposure.
Materials and Methods
This retrospective clinical noninterventional monocenter study was performed during the clinical routine without any further consequences for the patient. According to this and in accordance with the 1964 Declaration of Helsinki on medical protocol and ethics, no approval by the local ethics committee was necessary.
This study included 65 partially edentulous patients who underwent grafting procedures and dental implant placement in a Private Dental Practice, Bremen, Germany. All of them showed at least one highly atrophied segment of the jaws, which required further augmentation procedures to achieve implant placement with long-term bone stability. In total, 70 maxillary or mandibular alveolar sites had to be treated by the same trained surgeon (H.H.). All ridge augmentations were performed by using an individualized customized titanium mesh (Yxoss CBR; ReOss, Filderstadt, Germany).
Exclusion criteria were previous orofacial pain issues, previous squamous cell carcinoma of the oral cavity or oropharynx or other known tumor entities, and previous irradiation of the neck and face. Patients with other systemic diseases influencing the surgery protocol and local irritations were excluded. Patients who required implant placement without augmentation procedures or ridge expansion were also excluded from this study.
Patients and augmentation sites were evaluated focusing on defect regions, defect and mesh sizes, healing difficulties, and possible risk factors such as smoking, periodontitis, tissue phenotype (“A” = thin and fragile phenotype, “B” = thick phenotype), additional sinus floor augmentation procedures, and diabetes. Special focus was set to healing disorders of the soft tissue and grafting potential judged according to the developed dehiscence classification. A punctual exposure of the titanium mesh was classified as “A,” an exposure according to one tooth width (premolar) as “B,” and a complete exposure as “C.” No exposure of the meshes was stated as “D.” Subtypes documented loss of augmentation material with necessary regrafting (1 = partial and 2 = complete) and infection parameters such as 3 = swelling, 4 = pus, and 5 = fistula (Fig. 1).
Small dehiscences (“A”) were treated with anti-infectious agents such as topical application of chlorhexidine gel and rinsed at the office. More distinct dehiscences (“B”) were treated the same way for minimum 4 months, and in terms of “C,” a premature removal of the mesh and consequent soft-tissue healing was performed.
Loss of augmentation material was evaluated after the healing period in cases in which the outcome did not reflect the computer simulation performed at the beginning (Fig. 2). In addition, it was clinically determined by loosening of some grafting particles and an obvious volume deficit under the mesh, although a compact graft was established in the first surgery. After recognizing a partial or complete loss of grafting material (“1” or “2”), a regrafting was performed with an additional bone graft using GBR techniques (Bio-Oss particles; Geistlich, Wolhusen, Switzerland). If the recipient site was infected or too huge, no additional bone graft was applied.
Workflow and Surgery
The customized meshes were designed by generating a 3D model of the bony defect after acquisition of cone-beam computed tomography. They were manufactured in accordance with the desired augmentation volume by subtracting the bone from the model and correcting the developed design in three-dimensional projections by using CAD/CAM—procedures and rapid prototyping (Fig. 3). Final design of the lattice structures was confirmed interactively by the surgeon (H.H.).
All surgical treatments were performed under local anesthesia and followed the same protocol. Flap design was performed according to the principles of Kleinheinz et al.25 Full-thickness flaps were elevated to expose the bone, and scared tissue was removed. To enhance vascularization, perforations by means of small surgical burs were performed into the local bone. The meshes were installed by using a mixture of autogenous bone graft and Bio-Oss (Geistlich) particles in a 1:1 ratio (Fig. 4). Autogenous bone was harvested either from local bone or from the ramus by using a Safescraper (Biomet 3i, Munich, Germany). Each mesh was secured by means of one or more 1.5-mm titanium osteosynthesis screws (KLS Martin, Tuttlingen, Germany) on local bone to exclude micromovements.
Following the in vitro protocol of Choukroun,23 A-PRF was manufactured by the manufacturers' protocol, enriched with I-PRF and placed on the surface of the meshes (Fig. 5). In a double layer technique, a collagen membrane (Bio-Gide; Geistlich) was placed on top. Soft-tissue closure and sutures were performed without tension by using PTFE-Cytoplast 4.0 (American Dental Systems, Vaterstetten, Germany). Sutures were removed after 2 weeks.
Implant placement (Camlog Screw Line; Camlog, Wimsheim, Germany) was performed either simultaneously with mesh insertion or after a healing period of 4 to 6 months combined with the removal of Yxoss CBR (Fig. 6).
Patients were instructed to correct dental care and to avoid tooth brushing and trauma in the site of surgery. They were not allowed to wear removable dentures to avoid pressure on the soft tissue for the whole time of the grafting procedure. All patients underwent an oral antibiotic therapy (Amoxicillin STADA 1000 mg; STADAPHARM GmbH, Bad Vilbel, Germany 1-1-1 or Clindamycin; Aristo GmbH, Berlin, Germany 600 mg 1-1-1) for 5 to 7 days starting at the time of the surgery in combination with Solu-DecortinH 5 mg (Merck Pharma GmbH, Darmstadt, Germany). An antiseptic oral rinse (0.2% Chlorhexamed FORTE without alcohol, GlaxoSmithKline Consumer Healthcare GmbH & Co. KG—OTC Medicines, München, Germany) was recommended for application 3 times per day for 1 week.
Data are presented as mean ± SD. For statistic comparison of collected data, the Mann-Whitney test and t test were used. Statistical assessment was performed using IBM SPSS Statistics version 23.0 for Windows. Relevant differences in results were considered in cases P > 0.05. For presentation of data, JMP 10.0 statistical software (SAS Institute, Cary, NC) was used.
This study evaluated 70 customized lattice structures in 65 patients. Thirty-six patients (55.4%) were women and 29 men (44.6%), with a mean age of 60.55 years (range of age 23–82 years with SD = ±11.3 years). Tobacco abuses were documented in 11 (16.9%) and a periodontal disease in 35 patients (53.8%). Four patients (6.2%) suffered from stable diabetes mellitus (HbA1c <5%). A thin tissue phenotype “A” was documented in 38 cases (54.3%) and a thick phenotype “B” in 32 cases (45.7%).
Bone loss geometry was horizontal in 1 case (1.4%), 4 cases showed a vertical deficit (5.7%), and 3-dimensional loss occurred in 65 cases (92.9%). Sixty-two patients underwent surgery with one mesh (95.4%), 2 patients received 2 (3.2%), and 1 patient received 3 meshes (1.5%). In 8 cases (11.4%), implant placement was performed simultaneously, and in 62 cases (88.6%), the augmentation procedure was first and implant placement was performed in sense of second-stage surgery. The augmentation site was in the upper jaw (47.1%) and in the lower jaw (52.9%). Twenty-one customized lattice structures were placed in the anterior region (30%), 46 in the posterior region of the jaws (65.7%), and in 3 cases (4.3%), the augmentation site was in the anterior and posterior region. Size of lattice structure was designed to replace 1 to 2 teeth (46 cases, 65.7%), 3 to 4 teeth (21 cases, 30%), and >5 teeth (3 cases, 4.3%). Simultaneous maxillary sinus floor augmentation was performed in 9 cases (12.9%).
In total, 37.1% exposures of the meshes occurred. According to classification, 13 meshes (18.6%) were group “A,” “B” was found in 7 cases (10%), and group “C” consisted of 6 cases (8.6%). No exposure (“D”) was seen in 44 cases (62.9%; Fig. 7).
Loss of augmentation material (0–2)
Subtypes revealed a partial loss of augmentation material (“1”) in 23 cases (32.9%), 5 cases (7.1%) of complete loss (“2”), and a stable and profound augmentation site (“0”) in 42 cases (60%; Fig. 8). After regrafting procedures and the respective healing time, implant placement was not possible in 2 cases (2.9%).
Infection in sense of swelling (“3”) was documented in 2 cases (2.9%) and pus (“4”) in 9 cases (12.86%). Fifty-nine cases (84.3%) showed no sign of infection (Fig. 9). Fistula (“5”) was not documented.
Risk Factors for Dehiscences
Age (P = 0.67), gender (P = 0.8), tobacco abuse (P = 0.178), diabetes (P = 0.636), periodontitis (P = 0.313), and tissue phenotype (P = 0.14) had no influence on dehiscence probability. Other potential risk factors such as amount of meshes in one patient (P = 1), localization (upper/lower jaw [P = 1]), anterior/posterior/combination (P = 0.389), sizes of meshes (P = 0.248), or simultaneous sinus floor elevation (P = 0.292) were not relevant for the occurrence of dehiscence. Simultaneous placement of implants did not show a correlation with exposure of the mesh (P = 0.472) and the number of implants (P = 0.372). Potential infection did not influence the development of dehiscences (P = 0.157). Defect geometry did not correlate with dehiscence probability (P = 0.204). Exposure of the mesh was significantly associated with implant loss (P < 0.001).
Evaluation of Loss of Grafting Material (0–2) in Cases With Exposure (A–D)
Age (P = 0.67), gender (P = 0.66), periodontitis (P = 0.092), tissue phenotype (P = 1), and diabetes (P = 1) had no influence on graft loss in cases of exposure. When the meshes were exposed, tobacco abuse proved to be associated with a significantly higher amount of loss of the grafting material (P = 0.032). The amount of meshes in one patient (P = 0.606), localization (upper/lower jaw P = 0.058 and anterior/posterior/combination P = 0.627), and size of mesh (P = 0.195) did not influence bone loss in cases of premature exposure. When dehiscences occurred, mesh augmentation procedures associated with sinus floor elevation techniques showed significantly more loss of the grafting material (P = 0.001). When the meshes were exposed, the numbers of implants did not show a correlation with bone loss (P = 0.607) and defect geometry (P = 0.087). In total, exposure (“A–C”) was significantly associated with more loss of grafting material (0 < 0.001).
Correlation Between Classification Parameters and Bone Loss
Evaluating the classification parameters (A–D) regarding potential loss of the grafting material, “A” showed significantly more partial loss than “B,” “C,” and “D” (A > B > C > D; P < 0.001). Group A was associated with partial loss of the grafted material (“1”) in 10 of 13 cases but never associated with total loss (“2”). There was significantly more loss of grafting material when pus was seen (0.007).
The use of titanium mesh in terms of GBR techniques is a well-known procedure for 3-dimensional bone reconstruction. New customized products intend to offer the opportunity for predictable bone grafting in complex cases. Reduced surgery time by avoiding a challenging and time-consuming intraoperative manual shaping of the titanium mesh will be one of these benefits.11,20,26–28 Soft-tissue management remains one of the most challenging issues in terms of these techniques.29 The original contribution of this study was to evaluate soft tissue, risk and predictive parameters for success in customized bone regeneration according to a new classification. A retrospective study design was used to analyze 70 cases treated with patient-specific titanium meshes and to identify factors that might be associated with postoperative complications such as exposure of the mesh or graft failure.
The results show that tobacco abuse had no influence on dehiscence probability, but smokers had significant more loss of the grafting material in cases of dehiscences. This is in accordance with Lindfors et al,18 who reported statistically significant (P = 0.031) differences in the success rates regarding augmentation outcome between smokers (62.5% success rate) and nonsmokers (94.7% success rate). They also stated no correlation between smoking and the development of exposures. In general, smoking is well known to affect healing processes in terms of GBR because it is known to hinder bone revascularization and to increase soft-tissue inflammation.18 Its vasoconstrictive function and its negative influence on regenerative effectors such as fibroblasts30 and polymorphonuclear leukocytes31 inhibit sufficient tissue recovery. It is tempting to speculate that increasing tobacco consumption leads to an increasing regeneration deficit. However, this has to be assessed in further studies.
Diabetes was not found to have an influence on developing dehiscences or grafting failure. All patients with diabetes included in this study are well-controlled type 2 diabetic patients indicating staged GBR as a feasible augmentation procedure in many cases as reported by Erdogan et al.32 However, studies also reveal that severe, uncontrolled diabetes negatively influences the wound healing in sense of a higher number of infectious complications,33 implicating the need for a correct adjustment of the diabetic metabolism before initiating surgery in the oral area.
According to general clinical experience, a thin tissue phenotype might lead to an earlier mucosal rupture with consecutive loss of augmentation material. In the study by Lindfors et al,18 50% of the exposure rate was associated with a thin phenotype. On the contrary, the findings of this study at hand indicate that a thin phenotype (“A”) poses no increasing risk of the development of dehiscences and loss of grafting material. Therefore, clinical experience should be reconsidered. The same applies to factors of age, gender, and periodontitis, which did not influence the rate of dehiscence and loss of bone graft. Neither the amount of meshes placed in the individual patient nor localization or sizes of meshes were relevant for the occurrence of dehiscences and grafting failure. This is in accordance with Her et al,19 who reported no significant difference in the exposure rate between the maxilla and mandible. Louis et al34 concluded that a porous titanium mesh is a reliable containment system for reconstruction of the maxilla and the mandible. Evaluating the exposure of titanium mesh retrospectively, Uehara et al35 found a significant correlation between the success rate and the extension of the augmentation site. These findings are contrary to our results but might be due to different techniques in flap management as well. Simultaneous implant placement and number of implants did not reveal a correlation with the development of dehiscences and loss of grafting material.
According to our data, sinus floor elevation was not relevant for the occurrence of dehiscence. However, statistically significant more graft failures associated with sinus floor elevation in cases of dehiscences were seen. Representing a failure of therapy, 2 cases with additional sinus grafting with no exposure got infected and led to a complete loss of grafting material by developing an acute sinusitis. A regrafting was not possible yet. Although a consequent preselection of the patients was routine excluding cysts and chronic maxillary sinusitis,36 implants, titanium mesh, and grafting material had to be removed. Maxillary sinus floor elevation using a lateral approach has been proven to be the most successful bone augmentation procedure in terms of implant placement.37 Consequently, it is to assume that the grafting area including the lateral window approach and mesh insertion was too huge and promoted infection. A possible solution might be the splitting of the 2 grafting procedures. The new protocol should include initial grafting with titanium meshes and a second-step surgery including sinus floor elevation with removal of the mesh.
In the study at hand, mesh exposure (A–C) was found in 37.1% of cases. When comparing with the literature, heterogenous data of exposure rates are reported. In a study conducted by von Arx et al,17 even 50% of cases presented membrane exposures. Fifty-nine percent of complications occurred because of soft-tissue dehiscences in another study.38 Others described uneventful postoperative healing and found no dehiscences,39–41 as well as 14.8%,42 15%,18 35.3%,43 or even 52.27%34 of membrane exposure. In general, exposure of meshes was found to be the most frequent complication in GBR techniques using titanium meshes with a mean exposure rate of 16.1%.29 The different results may be due to various titanium mesh techniques used in these studies, possible improvement of the surgical procedures, various surgical skills, and diverse soft-tissue management or grafting procedures. Owing to the missing control group with a conventional titanium mesh, it is not possible to draw a conclusion to the superiority of individualized mesh regarding exposure or outcome rates in previous studies, although Sumida et al20 evaluated less exposure rates for customized meshes.
Concerning grafting material as a possible influencing parameter, Her et al19 found no differences between various materials. This is in contrast to Carini et al, who reported the use of autologous bone being associated with an increased gain of bone. Compared with other materials, they also evaluated a lower exposure of the mesh and a lower bone resorption.44 In most of the studies, there is no description of defect dimension. Interpreting the results from this study, all patients presented large defects, which would have made a conventional GBR technique with resorbable membranes impossible and would have required block augmentation from other intraoral or extraoral donor sites.
The results indicate that exposure (A–C) was significantly associated with more loss of grafting material,1,2 although this did not lead to a failure of therapy. A regrafting was possible, and implant placement could be performed except in the 2 cases without exposure as mentioned above. This is in accordance with other studies, which revealed that exposure during the healing period does not necessarily comprise the final treatment outcome.18,19,45 Although exposure of the titanium mesh had no negative impact,35 infection of the grafted material led to a lower success rate of the augmentation process. Other studies found a significant negative correlation between the amount of reconstructed bone and area of mesh exposed,46 which is similar to the data at hand.
Evaluating the single classification parameters (A–D) regarding potential loss of the grafting material, A showed significantly more partial bone loss when compared with B, C, and D (A > B > C > D). A possible explanation could be that mesh exposure may be accompanied by hosting food remnants and consecutively bacterial accumulation. To avoid infections, topical application of chlorhexidine gel on larger exposure sites (“B” and “C”) can help to prevent superinfection29 with a consecutive loss of grafting material. Only small mucosal perforations (A) may not be consequently treated according to this protocol, and a loss of some material may be a result. Obviously, it seems to be difficult for the patients to remove these remnants properly in terms of punctual exposure too. In these cases, it is necessary to have regular appointments with the surgeon to rinse and clean the mesh surface.
Revealing infection parameters, pus was accompanied by significantly more loss of grafting material. It is necessary to emphasize a perfect oral hygiene protocol at home and direct rinsing of the defect at the visits. Groups B and C with large mucosal perforations may lose the possibility to retract and mechanically stabilize the grafting material. Therefore, total loss of grafting material may take place. Interpreting the results from this study, mesh exposure should be avoided, and a focus on soft-tissue management should be set. Preoperative assessment should include planning of the flap, comparing different techniques and the necessity to mobilize the flaps to obtain a tension-free primary wound closure.29
In the literature, there is a lack of precise description on soft-tissue dehiscences concerning size and possible infection signs. Most of the studies only evaluate the fact of exposure appearance, and only some of them described the size in millimeter. It is necessary to distinguish between a partial and complete loss of augmentation material, possible regrafting as well as to include infection signs. According to our best knowledge, this is the first study that offers the possibility of a clinically relevant and reproducible classification including these factors. The classification proved to be a valid, clinical orientated method to specify dehiscences, and a precise description of the complications was possible.
Future protocols should aim to support soft-tissue healing. A promising solution may be the enhancement of soft-tissue wound healing by PRF as shown in a systematic review.47 PRF as a biodegradable scaffold consisting of stem cells, fibrin, platelets, and leukocytes and boosts microvascularization and epithelial cell migration. This may prevent mesh exposure by using it to cover conventional meshes as applied in this study. Comparing a PRP and control group, Torres et al22 reported 28.5% of the cases in the control group suffering from mesh exposure, whereas in the PRP group, no exposures were registered. Within the limitations of this study being retrospective and having no control group, we detected mesh exposure in individualized meshes (A–C) in 37.1% in a larger population. In addition, other resorbable membranes are discussed to favor the creeping attachment and to protect the graft from cell infiltration. But even in patients treated with titanium mesh, resorbable collagen membrane, and recombinant human platelet-derived growth factor BB (rhPDGF-BB), Funato et al48 experienced postoperative flap dehiscence. Kaner et al created more soft tissue to cover the grafted area by using self-inflating soft-tissue expanders. They draw a conclusion that this results in a decreased incidence of wound dehiscences in dogs.14,49 Kablan and Laster50 enhanced primary soft-tissue closure and prevented dehiscences with a free fat graft from the buccal fat pad. Nevertheless, these procedures may increase morbidity and need additional surgical skills.
The new surgical protocol including patient-specific titanium meshes Advanced- and Injectable-Platelet-Rich Fibrin (A- and I-PRF), resorbable membranes, and bone grafting materials was proven to be a promising technique in complex bone and soft-tissue reconstruction. This study applied a new exposure classification to describe soft tissue and grafting outcome. Soft-tissue management remains one of the most critical steps using an individualized CAD/CAM titanium mesh. Potential risk factors associated with this protocol were smoking and mesh insertion simultaneous with sinus floor elevation procedures. An adequate preselection of patients should be mandatory, and a splitting of the surgical procedures in terms of sinus floor elevation is mandatory.
As clinical recommendations, small dehiscences (“A”) might be treated with anti-infectious agents and rinsed professionally. The same procedure is advised for larger dehiscences (“B”), and in terms of “C,” a premature removal of the mesh and soft-tissue healing might facilitate further treatment. Loss of the grafting material might be compensated by regrafting if no infection is present.
The authors claim to have no financial interest, either directly or indirectly, in the products or information listed in the article.
This retrospective clinical noninterventional monocenter study was performed during the clinical routine without any further consequences for the patient. According to this and in accordance with the 1964 Declaration of Helsinki on medical protocol and ethics, no approval by the local ethics committee was necessary.
Roles/Contributions by Authors
A. Hartmann: Concept/design of the study, data collection, and drafting the article. H. Hildebrandt: Concept/design of the study, data collection, and drafting the article. J. Schmohl: Data analysis/interpretation, statistics, and critical revision of the article. P. W. Kämmerer: Data analysis/interpretation, statistics, and approval of the article.
The authors thank patients, nurses, and physicians for their support with patients' material and reports. Moreover, the authors thank all their colleagues for helpful discussions.
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