Alveolar Ridge Augmentation using Customized Zirconia Membranes: A Systematic Review

1. INTRODUCTION

Since the discovery of osseointegration and the development of intraosseous dental implants, the significance of alveolar bone in formulating treatment strategies for tooth replacement has become more prominent. The quantity of alveolar bone plays a crucial role, closely intertwined with the presence of teeth [1]. Research conducted over the years has consistently demonstrated inevitable bone resorption in both horizontal and vertical dimensions following tooth loss [2]. In addition to tooth loss, factors such as trauma, periodontal diseases, tumors, cysts, and other pathological conditions can also contribute to bone loss [2].

Researchers have made significant advancements in horizontal and vertical alveolar ridge augmentation techniques over the past few decades [3, 4]. These techniques are typically categorized into four main approaches: guided bone regeneration, bone block grafting, distraction osteogenesis, and osteoperiosteal flaps [5, 6]. Additionally, methods such as bone expansion and splitting are utilized for horizontal augmentation [7], while external and transalveolar sinus lift techniques are employed for vertical augmentation [8].

Guided bone regeneration is a widely used technique in oral and maxillofacial surgery clinics [9]. The fundamental principle involves creating a space between the host bone and soft tissues, which is then preserved using space-maintaining devices. Subsequently, the defect is filled with living bone [10]. An essential aspect of the success of guided bone regeneration is inhibiting the growth and proliferation of non-osseous cells in the targeted bone regeneration area. Barrier membranes are commonly utilized for this purpose [11].

The most frequently employed membranes in guided bone regeneration are resorbable collagen membranes and non-resorbable PTFE membranes [12]. These membranes possess excellent barrier properties that effectively prevent the infiltration of undesired cells into the bone defect. However, their space-maintaining capability is restricted, making them unsuitable for extensive bone augmentation procedures [13]. In such cases, titanium meshes and PTF titanium-reinforced membranes have been utilized as alternatives to the aforementioned membranes for comprehensive bone augmentation procedures [13-15]. Despite their established clinical success and predictability, these techniques have several drawbacks, such as the requirement for customization to fit the shape and size of the bone defect, extended surgical duration, relatively elevated exposure rates leading to procedural failure, limited barrier effectiveness of titanium meshes, and lastly, their considerable cost [13-15].

In recent times, 3D printing techniques have been integrated into the realm of bone regeneration through both additive and subtractive methodologies [16]. Initially, models were printed to replicate the patient's bone defect area, facilitating the pre-conditioning of titanium meshes, thereby streamlining the process. Subsequently, researchers utilized 3D printing or milling to create scaffolds from various materials ready for direct clinical implementation on the host site. Lastly, individualized container shells, often referred to as customized membranes, were fabricated using 3D printing or milling techniques [17].

Customized membranes can be described as space-maintaining devices tailored and produced to suit a specific bone defect aimed at rehabilitation of the area with dental implants. Initially, customized membranes were printed from titanium, the most extensively acknowledged and utilized metal in the domain of oral and maxillofacial surgery [18, 19].

Customized titanium meshes have demonstrated superior success rates compared to prefabricated meshes in terms of reducing complications, enhancing clinical outcomes, promoting bone gain, and streamlining the surgical process [16, 18]. Although titanium meshes have proven effective, their high cost has led researchers to explore zirconia as a potential alternative material for producing customized zirconia membranes to augment the alveolar ridge [20-26]. This systematic review seeks to assess the efficacy of customized zirconia membranes in alveolar bone augmentation.

The primary objective of this study is to offer a comprehensive review of various facets associated with the utilization of customized zirconia membranes, encompassing:

• Equipment and software employed for designing and fabricating customized zirconia membranes.
• Various design forms.
• Types of bone grafting materials utilized beneath these membranes.
• Assessment of bone gain, bone density, and histological analysis of newly formed bone.
• Identification of potential complications, their underlying causes, and strategies for prevention.

2. METHODS

The present systematic review is reported in accordance with the guidelines for the Transparent Reporting of Systematic Reviews and Meta-analyses [27, 28] following the 2020 Prisma Guidelines [29]. The study protocol was prospectively registered on PROSPERO (CRD42024588058).

3. RESULTS

3.1. Inclusion and Exclusion of Articles

The electronic search initially yielded 539 articles. Following deduplication, 263 unique articles remained. Subsequent manual screening of titles and abstracts led to the exclusion of 250 articles, resulting in 13 remaining articles. After conducting a thorough full-text assessment of these 13 articles to verify adherence to the inclusion/exclusion criteria, 6 articles were further excluded, leaving a total of 7 articles included in this review [20-26]. A flow diagram reporting the screening and selection of studies is presented in Fig. (1).

Table 1.

Article No.	Authors/Refs	Year	Journal	Type
1	Malmstrom et al. [20]	2016	International Journal of Oral and Maxillofacial Surgery	Case series
2	Hofferber et al. [22]	2018	The Journal of Implant & Advanced Clinical Dentistry	Two case report
3	Heikal et al. [23]	2020	Al-Azhar Journal of Dental Science	Case series
4	Mandelli et al. [24]	2021	Journal of Dentistry	Case series
5	Souidan et al. [21]	2023	Alexandria Dental Journal	Case series
6	Joseph et al. [25]	2024	South Asian Research Journal of Oral and Dental Sciences	Case Report
7	Albash et al. [26]	2024	The Open Dentistry Journal	Case report

3.5. Description of Membranes

The membranes utilized in the included articles were predominantly designed similarly, albeit with distinct software and milling processes. They were custom-designed after importing the patient's Digital Imaging and Communications in Medicine (DICOM) files into the respective processing software. Through these software tools, the membrane was digitally crafted, milled, and then sintered using specialized equipment. Each membrane was uniquely dimensioned to precisely fit the specific area of the bone defect in each patient (Table 4).

Table 2.

Authors/Year	Type	A1	A2	A3	A4	A5	A6	A7	A8	A9	A10	Total of Yes
Malmstrom 2016 [20]	Case series	No	Yes	Yes	No	No	No	Yes	Yes	Yes	Yes	6/10
Hofferber 2018 [22]	Case report	No	Yes	Yes	Yes	Yes	Yes	No	Yes	-	-	6/8
Heikal 2020 [23]	Case series	Yes	Yes	Yes	No	No	No	Yes	Yes	Yes	Yes	7/10
Mandelli 2021 [24]	Case series	No	Yes	Yes	No	No	No	Yes	Yes	Yes	Yes	6/10
Souidan 2023 [21]	Case series	Yes	Yes	Yes	No	No	No	Yes	Yes	Yes	Yes	7/10
Joseph 2024 [25]	Case report	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	-	-	7/8
Albash 2024 [26]	Case report	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes	-	-	7/8

Table 3.

Article No.	Authors/Refs.	Number of Patients	Number of Procedures	Age	Gender
-					Male	Female
1	Malmstrom [20]	3	4	50.66 ±18.03	1	2
2	Hofferber [22]	2	2	37 ± 1.41	1	1
3	Heikal [23]	7	14	55.86±4.6	3	4
4	Mandelli [24]	7	9	63.1 ± 6.2	2	5
5	Souidan [21]	10	10	29.60 ± 6.83	4	6
6	Joseph [25]	1	1	25 ± 0	1	0
7	Albash [26]	1	1	20 ± 0	0	1
-	Total	31	41	45.83 ± 16.35	12	19

Table 4.

Authors/Refs.	Thickness	Milling Machine	Milling Machine Trading Name	Zirconia Disc	Sintering Temperature	Software	Sterilization	Porosity	Screws Number
Malmstrom 2016 [20]	0.7	5-axis	Dechel-Maho, DMU 60, Deckel Maho, Pfronten, Germany	TZ3YSEB; Tosoh	1450°C	-	Autoclave 134°C	Non-porous	1
Hofferber 2018 [22]	-	5-axis	CORiTEC 350i, imesicore GmbH	Zenostar MO, Ivoclar Vivadent	-	Materialise, Leuven, Belgium	-	Porous	1
Heikal 2020 [23]	-	5-axis	Ceramill motion 2 5x, Amann Girrbach, Lichtenstein	-	-	-	-	Non-porous	Multiple
Mandelli 2021 [24]	0.4–0.5	5-axis	M1, Zirkonzahn, Gais, Italy	Prettau, Zirkonzahn, Gais, Italy	-	Exocad GmbH, Germany	Autoclave 134°C for 18 min	Non-porous	Multiple
Souidan 2023 [21]	0.7	5-axis	Roland DWX 50®, Japan	Dental Direct®, Germany	1500°C	Blueskybio, Illinois, US	Autoclave 134°C	Non-porous	Multiple
Joseph 2024 [25]	-	5-axis	PrograMill PM7, Ivoclar, Schaan, Liechtenstein	Ivoclar Vivadent	-	MeshMixer, Autodesk, San Rafael, CA	-	Non-porous	Multiple
Albash 2024 [26]	0.5 - 1	5-axis	Roland DWX 50®, Japan	Dental Direct®, Germany	1500°C	Exocad GmbH, Germany	-	Non-porous	1

Certain authors mentioned that they designed the dimensions and morphology of the virtual bone with consideration for future prosthetics (prosthetically designed guided), ensuring that subsequent dental implants could be placed to align appropriately with the future prosthesis. However, not all authors detailed this aspect in their reports.

In the design process, special holes were created for fixation screws. Some authors noted that a single fixation screw proved adequate to stabilize the membrane and prevent movement. Conversely, in cases of more extensive bone defects, other authors opted for multiple fixation screws (Fig. 3). While the thickness of the membranes varied across studies, it generally did not exceed one millimeter in most instances (Table 4).

Except for the membranes employed in the Hofferber et al. [22] study, which were porous, all other membranes used in the reviewed cases were nonporous (Fig. 4 and Table 4).

Across all studies, the CZMs were designed as a single continuous piece, except Joseph et al. [25] study, where the CZM was divided into two separate pieces—a buccal piece and a palatal piece (Fig. 5).

3.6. Bone Graft Material and Defect Features

This review encompassed three specific regions of the jaws: the anterior region of the maxilla, where 13 procedures were conducted; the posterior region of the maxilla, where 9 procedures took place; and the posterior region of the mandible, where 18 procedures were carried out (Table 4).

Various bone graft materials were employed across the studies included in this review. The most prevalent choice was xenogeneic (bovine) bone graft, utilized in 17 procedures, constituting 42.5% of the cases. A combi- nation of graft materials was employed in 10 procedures, accounting for 25% of the total. Additionally, two cases utilized allografts solely, while one case utilized an autograft harvested from the same recipient site. Notably, in 10 procedures (25%), no bone graft materials were utilized (Table 4).

Bone defects were categorized as either vertical only, horizontal only, or both vertical and horizontal. Out of the included studies, five reported the specific type of bone defect addressed, involving a total of 23 patients and 31 procedures. Only one study did not provide this information, encompassing 7 patients and 9 procedures. Upon review, the distribution of bone defects managed in the included studies was as follows: 4 cases of vertical defects only, 8 cases of horizontal defects only, and 19 cases involving both horizontal and vertical defects (Table 5).

Table 5.

Authors/Refs.	Region			Defect			Bone Graft
	Anterior Maxillary	Posterior Maxillary	Posterior Mandibular	Vertical	Horizontal	Horizontal & Vertical	Auto	Allo	Xeno	Mix	No Bone Graft
Malmstrom [20]	1	1	2	4	0	0	1	0	0	0	3
Hofferber [22]	1	0	1	0	1	1	0	1	0	1	0
Heikal [23]	0	0	14	0	0	14	0	0	7	0	7
Mandelli [24]	0	8	1	-	-	-	0	0	0	9	0
Souidan [21]	10	0	0	0	6	4	0	0	10	0	0
Joseph [25]	1	0	0	0	0	1	0	1	0	0	0
Albash [26]	1	0	0	0	1	0	0	1	0	0	0
Total	13	9	18	4	8	20	1	3	17	10	10

Table 6.

Authors/Refs.	Bone Gain				Bone Density
	Vertical	N	Horizontal	N
Malmstrom [20]	2.9 ± 1.126	3	0	0	-
Hofferber [22]	3	1	3.5 ± 0.353	2	-
Heikal [23]	2.44 ± 0.92	14	1.76 ± 0.55	14	465.9 ± 367.9
Mandelli [24]	-	-	-	-	-
Souidan [21]	5.58 ± 1.26	4	2.18 ± 1.05	10	806.39 ± 206.76
Joseph [25]	-	-	-	-	-
Albash [26]	0	0	5.55	1	-

3.8. Histological Analysis

The authors of the majority of studies included in this review noted the presence of a soft tissue layer between the membrane and the newly formed bone (Fig. 6). Three of the studies conducted histological analysis on this soft tissue layer and observed it to be a connective tissue resembling the periosteum, with no signs of inflammatory response. Histological examination of bone biopsies revealed typical osteoblast and osteoclast activity, along with dilated vessels characterized by thin walls.

Table 7.

Authors/Refs.	Number of procedures	Premature membrane exposure	Week	Possible causes	Loss of bone graft materials	Augmentation failure
Malmstrom [20]	4	0	-	-	0	0
Hofferber [22]	2	0	-	-	0	0
Heikal [23]	14	0	-	-	0	0
Mandelli [24]	9	1	4	Suboptimal membrane design with sharp edges.	0	0
Souidan [21]	10	9	5.80 ± 5.53	Suboptimal membrane design. Absence of periosteal sutures. Palatally based incision line. Excessive palatal extension. Anterior maxillary region.	1	0
Joseph [25]	1	1	13	-	0	0
Albash [26]	1	0	-	-	0	0

4. DISCUSSION

This study aimed to conduct a systematic review of the literature on the use of customized zirconia membranes for alveolar ridge augmentation. The review specifically focused on case series and case reports, as no randomized clinical studies, cohort studies, or long-term clinical studies were found in the literature. The included articles in this review demonstrated a consistent approach in terms of design and surgical procedures, with only minor variations among them.

All authors of the articles included in this review utilized cone beam computed tomography (CBCT) scans for designing custom membranes. They employed special software to convert DICOM formats into STL formats understood by 3D printing machines. The fabrication of all membranes was carried out using CAD/CAM technology.

Except for two surgical case reports [22], the customized membrane designs were non-porous. The porosity of barrier membranes remains a topic of significant controversy among authors [30-32]. The non-porous nature of the barrier membranes offers two crucial conditions for guided bone regeneration: the ability to maintain space and effective barrier capacity [32]. The barrier capacity aims to prevent unwanted cells from infiltrating the bone defect area. Pores in porous membranes can allow these cells to penetrate, reducing the predictability of bone volume formation [32]. On the other hand, non-porous membranes block the blood supply from the tissues surrounding the defect area and limit the regenerative potential of the periosteum [31, 32]. The periosteum houses mesenchymal cells capable of osteoblast differentiation [30]. Porous membranes offer the advantage of preventing bacterial invasion of the defect area if the membrane becomes exposed [20, 24]. However, the presence of holes in the zirconia membrane may increase the risk of fracture, either during the milling stage or the fixation stage, due to its inherent brittleness [25].

All the membranes in the reviewed articles were designed as a single piece, except in Joseph's case report [25], where the customized zirconia membrane was designed as two pieces that could be bonded together (Fig. 5). Joseph et al. [25] rationalized this design, stating that it eases the insertion of bone graft material under the membrane, ensuring a complete seal and eliminating gaps. Joseph et al. [25] also mentioned another rationale for this design, stating that the two-piece membrane design makes it easier to remove in cases where there is an undercut area hindering the device's removal. Furthermore, this design could potentially facilitate the creation of larger membranes suitable for accommodating large bone defects [25].

All authors noted the snug fit of the membrane against the host bone, leading to improved primary stability of the membranes and a reduced need for screws during fixation. This close fit not only prevents the loss of bone graft material and bacterial invasion when the membrane is exposed but also streamlines the process by eliminating the time and effort needed for conditioning, as compared to prefabricated membranes and meshes [20, 25, 26].

All authors employing non-porous membranes observed the development of a soft tissue layer, termed pseudoperiosteum, between the membrane and the newly formed bone [20, 21, 23-26]. Although the specific mechanism underlying the formation of this layer remains unclear, authors conducting histological analyses of this layer noted its absence of adverse effects or inflammatory responses, showcasing the excellent biocompatibility of zirconia [33]. An additional benefit of this layer is the ease of membrane removal [24, 25]. It is notable in all cases that the membranes lack integration and adhesion to soft and hard tissues, a phenomenon that remains unclear but aids in the straightforward removal of the membrane. This stands in contrast to other materials used in membrane production, which may necessitate significant time and effort for membrane removal [24].

Space maintenance is a crucial aspect of bone augmentation procedures, particularly in vertical bone defects [34-36]. Zirconia membranes have demonstrated effective space maintenance, which is attributed to their strength, which withstands soft tissue stress and prevents space collapse [20-26]. This phenomenon is often attributed to the thorough filling of the designated space with living bone, as emphasized by the majority of authors [20, 21, 24]. While hardness and toughness are crucial for space maintenance, zirconia exhibits brittleness, fragility, and inflexibility, rendering it intolerant to design or manufacturing errors and susceptible to breakage during milling or fixation [20, 22-24]. In a study conducted by Albash et al. [26], they opted to fabricate two identical membranes as a precaution. Mandeli et al. [24] highlighted the importance of careful screw tightening during fixation to prevent over-tightening and potential breakage.

In our review, it was noted that authors utilized various types of bone grafting materials, including autologous, allogeneic, and xenogeneic, except for alloplastic, and in some cases, no bone grafts were placed beneath the membranes. Heikal et al. [23], in their study comparing the use of zirconia membranes with and without grafts, highlighted a statistically significant difference in the volume and density of bone formation, favoring the group that received grafts [23]. The studies did not include follow-up periods exceeding 7 months, prompting consideration regarding the feasibility of employing bone grafts necessitating extended healing durations [20]. Malmstrom et al. [20], in their study involving three cases, reported a follow-up period of approximately 7 months, noting no adverse reactions to the presence of the membranes within the tissues [20]. Consequently, they proposed the potential use of zirconia membranes in conjunction with bone grafts requiring extended healing periods, such as alloplastic grafts [20].

Concerning premature membrane exposure, the majority of authors observed excellent soft tissue responses to zirconia membranes, with minimal instances of premature exposure reported during the follow-up period. In our review, the membrane exposure rate was found to be 26%, predominantly in the study by Souidan et al. (90% of cases) [21]. When excluding the Souidan et al. study from this review, the exposure rate decreased significantly to only 6.5%, which is notably lower than the exposure rates associated with prefabricated [37] or customized titanium meshes [38]. Souidan et al. [21] attributed the high rate of premature membrane exposure to factors such as design errors (suboptimal membrane design or excessive palatal extension), surgical errors (absence of periosteal sutures or palatally based incision line), or the specific location of the bone defect (anterior area of the maxilla characterized by strong muscle pull due to lip movement) [21].

CONCLUSION

While all studies included in this review were case series or case reports, customized zirconia membranes are highly effective in both localized and generalized bone augmentation procedures. These membranes exhibit high biocompatibility, superior space-maintenance capacity, excellent barrier capacity (non-porosity), ease of removal, and a close fit with the host bone.

Compared to custom or prefabricated titanium membranes, zirconia membranes display a relatively low rate of exposure. Their snug fit and excellent primary stability serve to safeguard the bone graft material from potential loss or bacterial contamination in case of membrane exposure. Nonetheless, caution is advised during usage due to their brittleness and vulnerability to fracture under high force, particularly during screw tightening.

We recommend conducting long-term randomized clinical trials to provide a more thorough evaluation of their efficacy. Additionally, we suggest comparing porous membranes with non-porous membranes in clinical trials, as well as exploring the use of alloplastic bone grafts beneath these membranes.

REFERENCES