Abstract
This systematic review aimed to identify and analyze in vitro studies on the marginal adaptation values of computer-aided-design/computer-aided-manufacturing (CAD/CAM) and heat-pressed lithium disilicate glass ceramics and zirconia-reinforced lithium silicates and endocrown restorations. A full literature search was conducted in Web of Science, PubMed/Medline, EMBASE, Scopus, Cochrane Library, Google Scholar, and ProQuest electronic databases. The following keywords: endocrown [(marginal adaption) or (marginal fit) or internal fitting)], endocrown [(molar(s)) or (premolar(s) or (posterior teeth) or (maxillary arch) or (mandibular arch)] and ceramic materials as [(lithium disilicate glass ceramic CAD/CAM) or (zirconia) or (heat-press)] were used. Articles were manually searched utilizing their reference lists. Study selection was restricted or limited to the time of publication but not to the type of tested teeth or ceramic material, endocrown design, system of endocrown construction, abutment scanning, and system of the marginal adaption measurement. A total of 17 in vitro studies published between 2016 and 2023 were included in this systemic review. Less than half of the studies were published during 2023. Most studies used lithium disilicate glass ceramic and zirconia-reinforced lithium silicate all-ceramic materials by CAD/CAM or heat-press systems. Marginal adaptation, or marginal gap, was almost equal in the 2 materials, while it was slightly or marginally higher in the heat-press than in the CAD/CAM system. All-ceramic lithium disilicate glass ceramic and/or zirconia endocrowns fabricated for posterior teeth in both arches using CAD/CAM or heat-press had recorded marginal adaptation values within an acceptable range.
Keywords: Dental Marginal Adaptation, Zirconium Oxide
Background
Endocrowns are monolithic conservative prostheses proposed as an alternative to the typical prosthodontic approach for rigorously compromised root canal treatment (RCT) teeth [1]. An endocrown consists of the crown and core in a single unit and is created with circumferential butt margin preparation and a retentive cavity inside the pulp chamber, without extending into it. While the pulp chamber is used for macromechanical retention, adhesive applications provide micromechanical retention [2,3]. Ceramic endocrown durability and success rates have been reported to be the same or better than that of a post-and-core and crown, with the advantages of conservative preparation, adhesive retention mechanism, fewer clinical and laboratory sessions, and possibility of use in teeth without ferrule [4]. Similarly, endocrowns have been suggested to restore RCT teeth with structurally variated bases or calcified or curved root canals that can prevent the insertion of a conventional post and core [5]. The main indications for endocrowns are lack of coronal dimension, inadequate interocclusal space, and considerable loss of tooth shape that results in insufficient ferrule extent [6].
Marginal adaptation is mostly evaluated by assessing the marginal gap, which is described as the distance between the internal surface of the restoration and the finish line of the preparation [7]. McLean and von Fraunhaufer concluded that 120 μm was the highest acceptable marginal opening [8]. Inadequate marginal adaptation can cause plaque accumulation, microleakage, caries, and endodontic inflammation, finally resulting in restoration failure [9]. Issues affecting marginal integrity are the extent of persisting enamel and dentin, form of scanning, cementation method, mode and bulk of materials, and preparation scheme [10,11]. Marginal bonding areas can be evaluated by different methods. Because it is a nondestructive and repeatable technique, stereomicroscope [12–18] followed by direct digital microscopic [19–21] examination of the marginal area is the most widely used method to measure the endocrown marginal adaption in different bonding areas, while micro-computed topography [22–25], scanning electron microscopy (SEM) [26,27], and other [28] systems can be used for endocrown marginal gap measurements.
Various ceramic systems are used for endocrown fabrications, such as feldspathic ceramics [26,27], lithium disilicate glass ceramics (LDGC) [13,15–19,22,23,25], and different types of zirconia [13,14,21], which have high mechanical strength and can be acid-etched. Zirconia and LDGC are considered the best choices owing to their mechanical and aesthetic features, including good anti-abrasion, anti-aging, and anti-corrosion properties, translucency, and biocompatibility with natural teeth. Other materials have been used for endocrown construction in laboratory studies [12,20].
The adhesive endocrown restoration option has been widely used recently as a successful alternative for the coronal seal restoration of RCT teeth. Conservatism, aesthetics, and minimum clinical and laboratory methods give this system its uniqueness compared with conventional post-and-core and crown procedures [12–28]. Most endocrowns are fabricated by computer-aided-design/computer-aided-manufacturing (CAD/CAM) or heat-press techniques [19,25,26] using various ceramic systems, such as LDGC and zirconia-reinforced lithium silicates, which are the most common all-ceramic materials used for endocrown constructions [29,30].
Endocrown ceramic material and adhesive system are used to obtain the monoblock concept, while some studies mentioned that there are various factors manipulating the prosthesis fitting, containment of preparation configuration, restriction location, and cement layer thickness and form [11,31]. The CAD/CAM system is vital, specifically for the marginal area. Defective prostheses milling makes the prostheses unable to seat correctly and can cause an installation with occlusal inconsistency. Moreover, additional milled material around the marginal contacts, microleakage, will result [25,26,32].
The general clinical steps of endocrown treatment and construction are shown in Figure 1, with the following images: (Figure 1A) a preoperative view of right mandibular first molar, (Figure 1B) view after RCT and intra-pulpal extension, (Figure 1C) view with cemented endocrown, and (Figure 1D) postoperative bite-wing radiograph showing the adaptation between the endocrown and tooth structure with a butt-joint preparation. In this systematic review, we aimed to identify and analyze in vitro studies on the marginal adaptation values of lithium disilicate glass ceramics and zirconia-reinforced lithium silicates in endocrown restorations.
Figure 1.
(A) Preoperative view of right mandibular first molar, (B) view after RCT and intra-pulpal extension, (C) view with cemented endocrown, and (D) postoperative bite-wing radiograph.
Material and Methods
Review Question
The present review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review (PRISMA; www.prisma-statement.org) statement [33,34]. The Population, Intervention, Comparison, Outcome (PICO) format was used to formulate the focused question according to Methley et al [35]: “Whether CAD/CAM or heat-press LDGC all-ceramic endocrowns (Intervention) used to restore RCT teeth (Population) exhibit superior marginal adaptation or minimum leakage (Outcome) compared with CAD/CAM or heat-press zirconia all-ceramic endocrowns (Comparison).”
Selection Criteria
The inclusion and eligibility criteria were as follows: (i) in vitro investigations assessing the fitting of all-ceramic endocrowns for RCT teeth, (ii) investigations assessing the marginal adaptation and marginal and axial discrepancy of RCT teeth, typodont, or natural teeth expressed as mean±the standard deviation and measured in micrometers (μm), and (iii) studies published in English. Studies involving RCT teeth treated for bovine teeth or using finite element analysis were excluded. Reviews, case reports, pilot studies, case series, editorials, clinical trials, and studies published in languages other than English were also excluded from the present systematic review.
Literature Search
The search strategy was performed using combinations of Medical Subject Headings (MeSH) terms and free keywords together with Boolean operators (ie, AND, OR, and NOT) with respect to the PICO question. An electronic literature search was performed on January 15, 2023, by 3 operators, which included a senior librarian specializing in health sciences database searches utilizing the following databases: Clarivate Analytics’ Web of Science, Elsevier’s Scopus, and PubMed (MEDLINE), without a restriction to studies after 2015 publication year. A manual search was then conducted by checking the bibliographies of all initially selected studies to identify articles that may have been missed during the electronic search.
Study Selection
The article selection process went through 3 stages: (i) selection based on title relevance, (ii) selection based on abstract relevance, and (iii) full-text analysis. All articles retrieved by manual and electronic searches were gathered and assessed for inclusion according to the eligibility criteria.
Data Extraction and Analysis
A standardized spreadsheet (Microsoft Office Excel software) was used to extract data of interest from the included articles. These data included (i) researchers and publication years, (ii) abutment type, arch, and tooth type, (iii) endocrown material and fabrication system used, (iv) endocrown preparation details, (v) method of preparation, impression type, use and thickness of die spacers, (vi) type of testing system and magnification size, (vii) mean values of marginal adaptation, marginal and axial discrepancy, or gap in different areas between the endocrown and materials used before and after cementation, expressed as mean±standard deviation in micrometers.
Quality Assessment
The methodological quality of the incorporated studies was evaluated using the parameters of previously published relevant systematic reviews involving in vitro investigations [36–38]. The risk of bias was judged according to the following variables: (i) sample randomization, (ii) single-operator protocol application, (iii) existence of a control group, (iv) blinding of the testing machine operator, (v) standardization of the specimen preparation, (vi) assessment of the failure mode, (vii) use of all materials in accordance with the manufacturer’s recommendations, and (viii) sample size calculation. A “yes” classification was assigned to an assessed variable if it was present in an article. If the information was not reported in the article, a “no” classification was assigned to the variable. The risk of bias of each individual article was categorized based on the total number of “yes” classifications received as follows: 1–3 (low quality/high risk of bias); 4–6 (medium quality/moderate risk of bias); and 7–8 (high quality/low risk of bias).
Results
Literature Search and Study Selection
The primary search resulted in 428 items. After removing 355 irrelevant and duplicate items and titles, we read the abstracts of 73 studies to exclude ineligible studies. A total of 56 studies were excluded, and 17 studies were selected for full-text retrieval. Finally, 17 studies were included in the present review [12–28]. Those studies measured the marginal adaptation or gap of endocrowns made by LDGC or zirconia ceramic materials measured in micrometers. The flowchart of the literature search process is illustrated in Figure 2.
Figure 2.
PRISMA flowchart of the study selection process.
Characteristics of the Studies
All included studies were in vitro studies [12–28]. The highest number of publications, 7 studies (41%), was from the year 2023 [12–15,19,20,22], followed by years between 2020 and 2022, with 6 studies (35%) [20,21,25–28]. Fourteen (76%) studies reported using natural teeth [12–15,17–23,25–27], 12 studies (71%) were for mandibular arches [13–17,19–20,22–25,27], and 11 studies (65%) were for molars [13–16,19,22–25,27,28]. LDGC and zirconia were the most common all-ceramic materials used for endocrown constructions, with 35% and 30%, respectively, and either alone or in comparisons with other all-ceramic materials. The manual abutment preparation for endocrowns was used in approximately 75% of studies [13–16,18,21–28], scanning was used in 90% of studies of endocrown preparation, while the stereomicroscope system was used in 40% of the total studies to record and assess the marginal adaptation in micrometers [12–18]. The information regarding the involved in vitro studies is presented, along with other characteristics, in Table 1. Figure 3 shows the detailed data of the included papers.
Table 1.
Summary of in vitro studies using lithium disilicate glass ceramic and zirconia all-ceramic materials.
| Researchers/Year | Abutment type/ arch/tooth type | EC material – fabrication system | Preparation details | |
|---|---|---|---|---|
| Nagi et al/ 2023 [22] | Human/ mandibular/molars | PEEK- CAD | Ferrule, but joint, partial coverage | |
| Ferrule, but joint, full coverage | ||||
| LDGC- CAD | Ferrule, but joint, partial coverage | |||
| Ferrule, but joint, full coverage | ||||
| Mertsöz et al/ 2023 [12] | Typodont/ maxillary/premolars | Ambarino High Class (RMC) - CAD | Ferrule, but joint, chamfer or shoulder finish line | |
| Voco Grandio (RMC)- CAD | ||||
| Brilliant Crios (RMC)- CAD | ||||
| Shofu (RMC)- CAD | ||||
| Attar et al/ 2023 [13] | Human/ mandibular/molars | VITA Suprinity- CAD | Butt-joint and 3 mm ferrule and 2 mm thickness | |
| LDGC- CAD | ||||
| Vita Enamic- CAD | ||||
| Jalali et al/ 2023 [14] | Human/ mandibular/molars | Celtra Duo- CAD | Butt-joint & 1.5 mm width. All walls were 3 mm height | |
| Only buccal wall reduced until 3 mm height | ||||
| Only lingual and one proximal wall reduced until 3 mm height | ||||
| Suliman and Rayyan al/ 2023 [15] | Human/ mandibular/molars | LDGC- CAD | Ferrule and butt joint margins with 3 mm intra-pulpal depth | |
| Elsayed et al/ 2023 [19] | Human/ mandibular/molars | LDGC- Press | Ferrule and cavity wall thickness 2.0 and intra-pulpal 5.0 mm | |
| Celtra Duo- Press | ||||
| LDGC- CAD | ||||
| Celtra Duo- CAD | ||||
| Arafa et al/ 2023 [20] | Human/ mandibular/premolars | 3D Printed- CAD | 2 mm ferrule, butt joint, 2 mm axial wall thickness | |
| Brilliant Crios (RMC)- CAD | ||||
| PEEK- CAD | ||||
| Soliman et al/ 2022 [21] | Human/ maxillary/premolars | Celtra Duo- CAD | No intra-radicular extension | |
| 3 mm intra-radicular extension | ||||
| Vita Enamic- CAD | No intra-radicular extension | |||
| 3 mm intra-radicular extension | ||||
| Abduljawad & Rayyan et al/ 2022 [25] | Human/ mandibular/molars | LDGC- CAD | 1.5 mm ferrule and butt-joints margins | |
| LDGC- Press | ||||
| Godil et al/ 2021 [16] | Typodont/ mandibular/molars | PEEK- CAD | 2 mm ferrule, butt joint and 3 mm intra-pulpal extension | |
| LDGC- CAD | ||||
| Sağlam et al/ 2021 [27] | Human/ mandibular/molars | LDGC- Press | 2 mm ferrule, 2 mm axial wall and 4 mm intra-pulpal | |
| Cerec Blocs- CAD | ||||
| Vita Enamic- CAD | ||||
| LDGC- CAD | ||||
| VITA Suprinity- | ||||
| Hassanzadeh et al/2021 [28] | Typodont/ maxillary/molars | Vita Enamic- CAD | Presence of ferrule, 3 mm axial wall and extension of 2 mm intra-pulpal | |
| LDGC- CAD | ||||
| VITA Suprinity- CAD | ||||
| Sağlam et al/ 2020 [26] | Human/ maxillary/premolars | Cerec Blocs- CAD | 2 mm ferrule, 2 mm axial wall and 4 mm intra-pulpal | |
| Vita Enamic- CAD | ||||
| Taha et al/ 2018 [17] | Human/ mandibular/premolars | LDGC- CAD | 2 mm ferrule, butt-joint, and 6mm intra-pulpal | |
| Vita Enamic- CAD | ||||
| Celtra Duo- CAD | ||||
| Cerasmart- CAD | ||||
| Rocca et al/ 2018 [18] | Human/ maxillary/premolars | LDGC- CAD | No ferrule and butt joint | |
| No ferrule, butt joint and 2 mm intra-pulpal | ||||
| No ferrule, butt joint and 4 mm intra-pulpal | ||||
| Ferrule, 5 mm intra-pulpal, 1mm chamfer | ||||
| Shin et al/ 2017 [23] | Human/ mandibular/molars | LDGC- CAD | Ferrule with 2.0 mm Preparation Depth | |
| Ferrule with 4.0 mm Preparation Depth | ||||
| Gaintantzopoulou et al/ 2016 [24] | Typodont/ mandibular/molars | Vita Enamic- CAD | 2.0 mm axial wall heights | |
| 2.0 mm axial wall heights+1.0 mm intra-radicular | ||||
| 2.0 mm axial wall heights+2.0 mm intra-radicular | ||||
| Researchers/Year | Preparation/ impression/spacer | Test system/ magnification size | Average mean values μm (±SD) | |
| Before cementation | After cementation | |||
| Nagi et al/ 2023 [22] | Manual/ Optical/ 0 margins & 50 μm other areas | Microcomputed tomography | MG: 64±11/Internal fit: 100±8 | |
| MG: 87±23/Internal fit: 104±19 | ||||
| MG: 98±11/Internal fit: 112±1 | ||||
| MG: 109±14/Internal fit: 127±1 | ||||
| Mertsöz et al/ 2023 [12] | Milling machine/ Optical/ NM | Stereomicroscope/ ×40 | MG: 31.20±6.28 | |
| MG: 36.53±12.01 | ||||
| MG: 27.58±4.34 | ||||
| MG: 33.63±8.56 | ||||
| Attar et al/ 2023 [13] | Manual/ Optical/ NM | Stereomicroscope/ ×80 | MG: 34.61±13.90 | |
| MG: 29.16±18.05 | ||||
| MG: 26.63±15.93 | ||||
| Jalali et al/ 2023 [14] | Manual/ Optical/ 60 μm | Stereomicroscope/ ×1.6 replica technique | AD: 129.06±26.35/MG: 170.32±53.07/ PD: 216.08±49.96 | |
| AD: 96.65±19.39/MG: 147.28±42.60/ PD: 205.43±44.19 | ||||
| AD: 108.99±19.33/MG: 160.99±30.25/ PD: 223.46±41.38 | ||||
| Suliman and Rayyan al/ 2023 [15] | Manual/Optical/ 40 μm | Stereomicroscope/ ×90 | MG: 46.25±21.20 | |
| Manual/Optical/ 80 μm | MG: 21.75±11.10 | |||
| Manual/Optical/ 120 μm | MG: 15.94±06.62 | |||
| Manual/Optical/ 160 μm | MG: 13.10±07.08 | |||
| Elsayed et al/ 2023 [19] | Milling machine/ Optical/50 μm | Digital microscope/ ×100 | MG: 25.5±7.04 | |
| Milling machine/ Optical/50 μm | MG: 31.4±5.89 | |||
| Milling machine/ Optical/50 μm | MG: 54.7±5.79 | |||
| Milling machine/ Optical/50 μm | MG: 60±8.23 | |||
| Arafa et al/ 2023 [20] | Manual and Operator/Optical/ 10 μm | Digital microscope/ ×40 | MG: 48.26±10.78 | MG: 59.44±8.08 |
| MG: 53.12±11.81 | MG: 65.42±12.39 | |||
| MG: 40.1±6.46 | MG: 51.49±8.41 | |||
| Soliman et al/ 2022 [21] | Manual/Optical/ NM | Digital microscope/ ×40 | MG: 7.74±1.55 | |
| MG: 29.54±6.32 | ||||
| MG: 10.42±3.63 | ||||
| MG: 25.63±12.96 | ||||
| Abduljawad & Rayyan et al/ 2022 [25] | Manual/Optical/ 80 μm | Microcomputed tomography | MG: 120±27/Line Angles: 130±37/ Cavity Walls: 140±43/Pulpal Floor: 240±58 | |
| Manual/intraoral scanner/80 μm | MG: 110±24/Line angles: 140±54/ Cavity Walls: 140±52/Pulpal Floor: 260±59 | |||
| Manual/laboratory scanner/80 μm | MG: 120±29/Line angles: 130±33/ Cavity Walls: 150±44/Pulpal Floor: 240±64 | |||
| Manual/Conventional/80 μm | MG: 150±35/Line angles: 280±70/ Cavity Walls: 210±76/Pulpal Floor: 500±150 | |||
| Godil et al/ 2021 [16] | Manual/Optical/ NM | Stereomicroscope/ ×50 | MG: 56.6±6.1/Internal gap: 158.2±11.1 | |
| MG: 81.3±10.1/Internal gap: 199.1±13.0 | ||||
| Sağlam et al/ 2021 [27] | Manual/Conventional/NM | SEM/×200 | MG: 122.49±28.37 | |
| Manual/Optical/NM | MG: 71.40±12.87 | |||
| Manual/Optical/NM | MG: 74.32±14.47 | |||
| Manual/Optical/NM | MG: 78.68±13.75 | |||
| Manual/Optical/NM | MG: 80.43±11.65 | |||
| Hassanzadeh et al/ 2021 [28] | Manual/Optical/ 6O.00 μm | Noncontact ATOS scanner | MG: 71.00±31.76/Axial: 77.16±23.78/ Occlusal-floor: 93.91±44.62 | |
| MG: 69.22±23.49/Axial: 70.18±14.03/ Occlusal-floor: 102.62±26.30 | ||||
| MG: 77.52±13.39/Axial: 73.36±19.86/ Occlusal-floor: 100.04±14.93 | ||||
| Sağlam et al/ 2020 [26] | Manual/Optical/NM | SEM/×200 | MG: 83.34±16.77 | |
| Manual/Optical/NM | MG: 69.70±10.77 | |||
| Taha et al/ 2018 [17] | Milling machine/Optical/NM | Stereomicroscope/ ×32 | MG: 36.9±24.4 | MG: 79.9±14.4 |
| MG: 47.01±26.6 | MG: 77.9±19.5 | |||
| MG: 45.8±16.6 | MG: 73.1±17.1 | |||
| MG: 39.4±17.8 | MG: 75.3±16.7 | |||
| Rocca et al/2018 [18] | Manual/Optical/NM | Stereomicroscope | MG: 81.5±23.25 | MG: 71.3±0.62 |
| MG: 87.5±22.44 | MG: 72.5±67.6 | |||
| MG: 93.2±92.82 | MG: 73.4±17.24 | |||
| MG: 93±92.45 | MG: 82.5±32.13 | |||
| Shin et al/ 2017 [23] | Manual/Optical/NM | Microtomography |
AD: 163.96±98.0 MG: 98.93±66.1 |
AD: 207.61±108.04 MG: 144.02±76.06 |
|
AD: 182.34±99.76 MG: 107.82±82.18 |
AD: 190.71±113.96 MG: 138.06±95.33 |
|||
| Gaintantzopoulou et al/2016 [24] | Manual/Optical/ 0.00 μm | Microtomography | MG: 40.6±4.1/MD: 65.9±12.1 | |
| MG: 48.9±13.8/MD: 76.2±12.0 | ||||
| MG: 59.4±9.6/MD: 77.6±5.9 | ||||
Celtra Duo-CAD – machinable zirconia-reinforced lithium disilicate glass ceramics; LDGC – lithium disilicate glass ceramics; Celtra-Press – pressable zirconia-reinforced lithium di silicate glass ceramics; VITA Suprinity – zirconia-reinforced lithium silicate glass-ceramic; RMC – resin-matrix ceramics; Cerasmar – resin nanoceramics; PEEK – polyetheretherketone; Vita Enamic – polymer infiltrated hybrid ceramic; Cerec Blocs – feldspathic ceramic; Lava Ultimate – resin-ceramic; NM – not mentioned; SEM – scanning electron microscopy; μm – micrometer; ±SD – ±standard deviation; AD – axial discrepancy; MD – marginal discrepancy; PD – pulpal discrepancy; MG – marginal gap; ML – marginal leakage.
Figure 3.
Characteristics of the included studies.
Marginal Adaption Outcomes
Figure 4 shows the values of marginal adaptation, or gap, of the endocrown materials and systems used in this review. Regarding the pulpal extension of the endocrown design and type of created finish line, the LDGC endocrowns had a slightly lower recorded marginal adaptation (55.66 μm) than did zirconia (62.34 μm) endocrowns. The pressable all-ceramic endocrowns had higher recorded marginal adaptation values than did the CAD/CAM systems, with 73.17 μm and 52.30 μm, respectively.
Figure 4.
Marginal adaptation values in micrometers (μm) for lithium disilicate glass ceramic and zirconia endocrowns of the included in vitro studies.
Results of Bias Assessment
Five studies did not have a single or blinded operator, and most of them did not have sample randomization or a control group. All studies recorded a standard sample size and marginal integrity and followed the manufacturer’s instructions. Out of the studies, only 1 study had a medium risk of bias [28], while the remaining scored a risk of bias of only 3, which is interpreted as a high level of bias [13,17,19,27]. Table 2 shows the quality bias assessment of the in vitro studies included in this systematic review.
Table 2.
Quality assessment of the included in vitro studies.
| Researchers/Year | Sample randomization | Single operator | Operator blinded | Control group | Standardized samples |
|---|---|---|---|---|---|
| Attar et al/2023 [13] | No | No | No | No | Yes |
| Elsayed et al/2023 [19] | No | No | No | No | Yes |
| Sağlam et al/2021 [27] | No | No | No | No | Yes |
| Hassanzadeh et al/2021 [28] | Yes | No | No | Yes | Yes |
| Taha et al/2018 [17] | No | No | No | Yes | Yes |
| Researchers/Year | Marginal integrity | Manufacturer’s instructions | Sample size calculation | Total score | Risk of bias |
| Attar et al/2023 [13] | Yes | Yes | Yes | 3 | High |
| Elsayed et al/2023 [19] | Yes | Yes | Yes | 3 | High |
| Sağlam et al/2021 [27] | Yes | Yes | Yes | 3 | High |
| Hassanzadeh et al/2021 [28] | Yes | Yes | Yes | 5 | Medium |
| Taha et al/2018 [17] | Yes | Yes | No | 3 | High |
Discussion
From a biomimetic perspective, preservation and conservation of the tooth structure are essential for maintaining the balance between biological, mechanical, adhesive, functional, and aesthetic factors of the dental element to be restored [39]. Endocrowns constructed by CAD/CAM or heat-pressed techniques are currently used for crowning of posterior maxillary and mandibular teeth after RCT. These endocrowns have a significant rate of survivability, and their success rate is described as equal or better than that of the post-and-core and crown, with the advantages of conservative preparation, adhesive retention devises, fewer clinical and laboratory sittings, and opportunity of practicing in teeth without ferrule [4,18,28]. In the present study, we conducted a systematic review to assess the behavior of marginal adaptation or marginal gap of machinable or pressable endocrowns constructed from LDGC and zirconia-reinforced lithium silicate ceramic materials.
Overall, and based on the outcomes of the in vitro studies included in this systematic review, the recorded values of the marginal fitting, gap, and marginal adaptation of both LDGC and zirconia endocrowns were within the clinically acceptable value of <120 μm [40,41]. Some in vitro studies documented equal or slightly higher marginal gap values, as documented by Jalali et al, with 160 μm for zirconia CAD/DAM [14], and by Shin et al, with 138 μm for LDGC CAD/CAM [23]. An equal value of marginal adaptation or slightly lower values were obvious in laboratory studies conducted by Sağlam et al for both LDGC and zirconia CAD/CAM [27], LDGC endocrowns constructed with CAD/CAM or heat-press systems [25], and LDGC manufactured by CAD/CAM [22]. Most of the studies recorded values ranging from 30 to 70 μm, as shown in Table 1. On the other hand, heat-pressed or CAD/CAM LDGC endocrowns had lower recorded marginal adaptation values than did zirconia endocrowns constructed by the same systems, as reported by Shafi and Rayyan and Ioannidis et al [42,43]. Those values are in agreement with the outcome of this review. Also, Riccitiello et al recorded similar marginal gap values of 65.0±23.0 μm, 69.0±41.0 μm, and 85.0±26.0 μm for CAD/CAM zirconia, CAD/CAM LDGC, and heat-pressed LDGC all-ceramic materials, respectively [44]. Recently, the mechanical behavior of LDGC endocrowns has been found to be parallel to that of post-and-core crowns [45].
CAD-CAM endocrown restorations that can affect CAD/CAM marginal fitting using intraoral optical scanners have been introduced. Recently, a systematic review by Turkyilmaz et al in 2023 showed that LDGC and zirconia all-ceramic CAD/CAM crowns offer parallel marginal gap values, but LDGC material presents an excellent internal fit, compared with that of zirconia [41]. Also, using SEM, the marginal gap documented by the zirconia material was 56.21±15.07 μm, as stated by Chouksey et al [46], while a lower value (21.45±12.58 μm) was recorded by Ferrini et al in 2023 for the same material, and marginally similar values were recorded for LDGC (62.28±51.8 μm) [40].
Marginal adaptation, defined as the gap between the finish line and the prostheses margin, is measured as one of the main criteria affecting the long-term prognosis of ceramic CAD/CAM prostheses [47]. Presence of a significant marginal gap between the tooth and the endocrown luting material will be visible to the oral location, resulting in luting dissolution and microleakage, leading to irritation of the gingival tissues, secondary caries, and finally endocrown failure [15–17,21–23,26–28]. The assessment of the marginal adaptation of prostheses is regularly accomplished using a simple technique with a digital microscope [19–21], stereomicroscope [12–15,17,18], or more advanced systems, such as SEM [26,27] and microcomputed tomography [22–25], as shown in Table 1. All systems used for endocrown marginal adaptation showed a high degree of accuracy and usually used the micrometer for assessments.
Endocrowns can be fabricated by CAD/CAM or heat-press techniques using various ceramic systems, such as lithium silicates and zirconia-reinforced lithium silicates [14,48,49]. A variety of the products are used in dental practice and produce prostheses with better accuracy of marginal variation [13,19,21]. The precision of CAD/CAM-fabricated endocrown fitting differs depending on the inspecting procedure, milling type step, post-milling dimensional differences, and configuration of the program used. Equally, the outline and width of the milling devices limit the machining of the inner outline, which can influence the final outcome in relation to the endocrown fitting [50]. To guarantee well-fitting prostheses, endocrowns can need reliable material dimensions, as they are somewhat brittle, and this can cause breakdown of the final products. The fit accuracy of prostheses assembled by heat-pressed porcelain resources has been shown to affect the durability and survival rate of the prostheses [21,32]. This is obvious in values recorded for machinable CAD/CAM materials as compared with pressable materials, as shown in Figure 4.
A second sintering step is required for most ceramic restorations involving CAD/CAM and heat-press techniques. Nevertheless, several reports have determined that the crystallization firing practice causes a substantial increase in the marginal gap size, possibly as shrinkage of the ceramic during the crystallization process [4,19,49,51]. However, other studies mentioned that there are various components affecting the fit of prostheses, incorporating preparation layout, parameter positioning, and cement nature and gap. CAD/CAM machinability is an essential factor, specifically for the part related to the marginal zone. Defective restoration milling indicates the lack of ability of the prostheses to seat correctly and can result in some occlusal inconsistency. Microleakage will be the outcome if too much material is milled around the marginal area of any restoration [21,32].
Attar et al, Soliman et al, and Oh et al determined that the scanning approach influences restoration precision [13,21,52]. According to the conclusions of Abduljawad et al and Son and Lee, the margin point, equigingival or subgingival, is able to impact restoration accurateness [25,53]. Likewise, the software model, record managing, and image triangulation technique affect the resolution and surface features of the last digital impression generated [54]. Other studies have shown that the 5-axis CAM element offered outstanding accuracy compared with the 4-axis element [12,14,55]. Moreover, the marginal adaptations of endocrowns are increased with additional preparation features and increased cavity height and divergence; therefore, declaring the preparation as simple as cavity design lead is proposed [56]. Many endocrown designs were used in this systematic review in relation to the height of ferrule, presence of butt-joint preparation, shape and length of the intra-pulpal extension, and material used with CAD/CAM or heat-press. Regardless, the marginal gap or adaptation recorded in all studies involved in this systematic review were similar and did not exceed the clinically acceptable recommended distance in micrometers.
Marginal discrepancy of endocrowns is intensified with adding preparation features, higher cavity depth and increasing the divergence. Fracture resistance of endocrowns is increased with more occlusal reduction and cavity depth
This systematic review, which used in vitro laboratory studies had some significant limitations. First, the methodologies used had high heterogeneity among the included studies. Second, most of the included studies were graded as having “high” quality bias. Third, variations in the dimensions (maxillary or mandibular) and types of endocrown teeth (molars or premolars) among the included studies may have resulted in differences in the marginal adaptation values stated. All of those limitations can affect the bonding strength and marginal durability of LDGC and zirconia.
Conclusions
From this systematic review, the following conclusions were drawn: all-ceramic LDGC and/or zirconia endocrowns fabricated for posterior teeth in both arches using CAD/CAM or heat-press had marginal adaptation values within an acceptable range. New in vitro investigations in which consistent material and measurement attempts are implemented are needed to strengthen the evidence currently presented in the literature regarding the durability of all-ceramic endocrowns.
Acknowledgement
I have to thank Dr Emad A Kamli at the Department of Restorative Dentistry, Specialized Jazan Dental Center, Ministry of Health, Jazan, Saudi Arabia for helping.
Footnotes
Conflict of interest: None declared
Publisher’s note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher
Declaration of Figures’ Authenticity: All figures submitted have been created by the authors, who confirm that the images are original with no duplication and have not been previously published in whole or in part.
Financial support: Financial support for this research was obtained by Deputyship for Research & Innovation, Ministry of Education, Jazan University, Saudi Arabia, through the project number ISP23-94
References
- 1.Sorensen JA, Engelman MJ. Ferrule design and fracture resistance of endodontically treated teeth. J Prosthet Dent. 1990;63(5):529–36. doi: 10.1016/0022-3913(90)90070-s. [DOI] [PubMed] [Google Scholar]
- 2.Bindl A, Mörmann WH. Clinical evaluation of adhesively placed Cerec endo-crowns after 2 years – preliminary results. J Adhes Dent. 1999;1(3):255–65. [PubMed] [Google Scholar]
- 3.Pissis P. Fabrication of a metal-free ceramic restoration utilizing the monobloc technique. Pract Periodontics Aesthet Dent. 1995;7(5):83–94. [PubMed] [Google Scholar]
- 4.Kanat-Ertürk B, Saridağ S, Köseler E, et al. Fracture strengths of endocrown restorations fabricated with different preparation depths and CAD/CAM materials. Dent Mater J. 2018;37(2):256–65. doi: 10.4012/dmj.2017-035. [DOI] [PubMed] [Google Scholar]
- 5.Adel S, Abo-Madina M, Abo-ElFarag S. Fracture strength of hybrid ceramic endocrown restoration with different preparation depths and designs. IOSR JDMS. 2019;18:17–23. [Google Scholar]
- 6.El-Damanhoury H, Haj-Ali H, Platt J. Fracture resistance and microleakage of endocrowns utilizing three CADCAM blocks. Operat Dentis. 2015;40:201–10. doi: 10.2341/13-143-L. [DOI] [PubMed] [Google Scholar]
- 7.Holmes JR, Bayne SC, Holland GA, Sulik WD. Considerations in measurement of marginal fit. J Prosthet Dent. 1989;62(4):405–8. doi: 10.1016/0022-3913(89)90170-4. [DOI] [PubMed] [Google Scholar]
- 8.McLean JW, von Fraunhofer JA. The estimation of cement film thickness by an in vivo technique. Br Dent J. 1971;131(3):107–11. doi: 10.1038/sj.bdj.4802708. [DOI] [PubMed] [Google Scholar]
- 9.Contrepois M, Soenen A, Bartala M, Laviole O. Marginal adaptation of ceramic crowns: A systematic review. J Prosthet Dent. 2013;110(6):447–54e10. doi: 10.1016/j.prosdent.2013.08.003. [DOI] [PubMed] [Google Scholar]
- 10.Mincik J, Urban D, Timkova S, Urban R. Fracture resistance of endodontically treated maxillary premolars restored by various direct filling materials: An in vitro study. Int J Biomater. 2016;2016:9138945. doi: 10.1155/2016/9138945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Kassem IA, Farrag IE, Zidan SM, et al. Marginal gap and fracture resistance of CAD/CAM ceramill COMP and cerasmart endocrowns for restoring endodontically treated molars bonded with two adhesive protocols: An in vitro study. Biomater Investig Dent. 2020;7(1):50–60. doi: 10.1080/26415275.2020.1728277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Mertsöz B, Ongun S, Ulusoy M. In-vitro investigation of marginal adaptation and fracture resistance of resin matrix ceramic endo-crown restorations. Materials. 2023;16:2059. doi: 10.3390/ma16052059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Attar E, Alshali S, Abuhaimed T. A comparative study of the marginal fit of endocrowns fabricated from three different computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic materials: An in vitro study. Cureus. 2023;15(6):e40081. doi: 10.7759/cureus.40081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Jalali S, Jalali H, Kharazi Fard MJ, et al. The effect of preparation design on the fracture resistance and adaptation of the CEREC ceramic endocrowns. Clin Exp Dent Res. 2023;9(3):518–25. doi: 10.1002/cre2.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Suliman O, Rayyan MR. The effect of cement space parameters on the marginal adaptation of milled endocrowns: An in vitro study. Cureus. 2023;15(5):e38688. doi: 10.7759/cureus.38688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Godil AZ, Kazi AI, Wadwan SA, et al. Comparative evaluation of marginal and internal fit of endocrowns using lithium disilicate and polyetheretherketone computer-aided design – computer-aided manufacturing (CAD-CAM) materials: An in vitro study. J Conserv Dent. 2021;24(2):190–94. doi: 10.4103/JCD.JCD_547_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Taha D, Spintzyk S, Sabet A, et al. Assessment of marginal adaptation and fracture resistance of endocrown restorations utilizing different machinable blocks subjected to thermomechanical aging. J Esthet Restor Dent. 2018;30(4):319–28. doi: 10.1111/jerd.12396. [DOI] [PubMed] [Google Scholar]
- 18.Rocca GT, Daher R, Saratti CM, et al. Restoration of severely damaged endodontically treated premolars: The influence of the endo-core length on marginal integrity and fatigue resistance of lithium disilicate CAD-CAM ceramic endocrowns. J Dent. 2018;68:41–50. doi: 10.1016/j.jdent.2017.10.011. [DOI] [PubMed] [Google Scholar]
- 19.Elsayed SM, Emam ZN, Abu-Nawareg M, et al. Marginal gap distance and cyclic fatigue loading for different all-ceramic endocrowns. Eur Rev Med Pharmacol Sci. 2023;27(3):879–87. doi: 10.26355/eurrev_202302_31180. [DOI] [PubMed] [Google Scholar]
- 20.Arafa A, Ziada A. Marginal adaptability and fracture resistance of endodontically treated premolars restored with 3D printed and milled endo-crowns. Egyptian Dental Journal. 2023;69(3):2137–52. [Google Scholar]
- 21.Soliman M, Alzahrani G, Alabdualataif F, et al. Impact of ceramic material and preparation design on marginal fit of endocrown restorations. Materials (Basel) 2022;15(16):5592. doi: 10.3390/ma15165592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Nagi N, Fouda AM, Bourauel C. Comparative evaluation of internal fit and marginal gap of endocrowns using lithium disilicate and polyether ether ketone materials – an in vitro study. BMC Oral Health. 2023;23:207. doi: 10.1186/s12903-023-02857-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Shin Y, Park S, Park JW, et al. Evaluation of the marginal and internal discrepancies of CAD-CAM endocrowns with different cavity depths: An in vitro study. J Prosthet Dent. 2017;117(1):109–15. doi: 10.1016/j.prosdent.2016.03.025. [DOI] [PubMed] [Google Scholar]
- 24.Gaintantzopoulou MD, El-Damanhoury HM. Effect of preparation depth on the marginal and internal adaptation of computer-aided design/computer-assisted manufacture endocrowns. Oper Dent. 2016;41(6):607–16. doi: 10.2341/15-146-L. [DOI] [PubMed] [Google Scholar]
- 25.Abduljawad DE, Rayyan MR. Marginal and internal fit of lithium disilicate endocrowns fabricated using conventional, digital, and combination techniques. J Esthet Restor Dent. 2022;34(4):707–14. doi: 10.1111/jerd.12902. [DOI] [PubMed] [Google Scholar]
- 26.Saglam G, Cengiz S, Karacaer O. Marginal adaptation and fracture resistance of feldspathic and polymer-infiltrated ceramic network CAD/CAM endocrowns for maxillary premolars. Niger J Clin Pract. 2020;23(1):1–6. doi: 10.4103/njcp.njcp_231_19. [DOI] [PubMed] [Google Scholar]
- 27.Sağlam G, Cengiz S, Karacaer Ö. Marginal adaptation and fracture strength of endocrowns manufactured with different restorative materials: SEM and mechanical evaluation. Microsc Res Tech. 2021;84(2):284–90. doi: 10.1002/jemt.23586. [DOI] [PubMed] [Google Scholar]
- 28.Hasanzade M, Sahebi M, Zarrati S, et al. Comparative evaluation of the internal and marginal adaptations of CAD/CAM endocrowns and crowns fabricated from three different materials. Int J Prosthodont. 2021;34(3):341–47. doi: 10.11607/ijp.6389. [DOI] [PubMed] [Google Scholar]
- 29.Al Moaleem MM, Al Ahmari NM, Alqahtani SM, et al. Unlocking endocrown restoration expertise among dentists: Insights from a multi-center cross-sectional study. Med Sci Monit. 2023;29:e940573. doi: 10.12659/MSM.940573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Al Ahmari NM, Gadah TS, Wafi SA, et al. Relationship between tooth type and material used in the construction of endocrowns and fracture force values: A systematic review. Eur Rev Med Pharmacol Sci. 2023;27:7673–87. doi: 10.26355/eurrev_202308_33420. [DOI] [PubMed] [Google Scholar]
- 31.Politano G, Fabianelli A, Papacchini F, Cerutti A. Use of bonded partial ceramic restorations to recover heavily compromised teeth. Int J Esthet Dent. 2016;11:314–36. [PubMed] [Google Scholar]
- 32.Zimmermann M, Valcanaia A, Neiva G, et al. Three-dimensional digital evaluation of the fit of endocrowns fabricated from different CAD/CAM materials. J Prosthodont. 2019;28(2):e504–e9. doi: 10.1111/jopr.12770. [DOI] [PubMed] [Google Scholar]
- 33.AlHelal AA. Biomechanical behavior of all-ceramic endocrowns fabricated using CAD/CAM: A systematic review. J Prosthodont Res. 2023 doi: 10.2186/jpr.JPR_D_22_00296. [Online ahead of print] [DOI] [PubMed] [Google Scholar]
- 34.Tribst JPM, Lo Giudice R, dos Santos AFC, et al. Lithium disilicate ceramic endocrown biomechanical response according to different pulp chamber extension angles and filling materials. Materials (Basel) 2021;14:1307. doi: 10.3390/ma14051307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Methley AM, Campbell S, Chew-Graham C, et al. PICO, PICOS and SPIDER: A comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res. 2014;14:579. doi: 10.1186/s12913-014-0579-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Bourgi R, Hardan L, Rivera-Gonzaga A, Cuevas-Suárez CE. Effect of warm-air stream for solvent evaporation on bond strength of adhesive systems: A systematic review and meta-analysis of in vitro studies. Int J Adhes Adhes. 2021;105:102794. [Google Scholar]
- 37.Zarow M, Dominiak M, Szczeklik K, et al. Effect of composite core materials on fracture resistance of endodontically treated teeth: A systematic review and meta-analysis of in vitro studies. Polymers (Basel) 2021;13:2251. doi: 10.3390/polym13142251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Nogueira IO, Oliveira PFG, Magno MB, et al. Does the application of an adhesive layer improve the bond strength of etched and silanized glass-ceramics to resin-based materials? A systematic review and meta-analysis. J Prosthet Dent. 2021;125:56–64. doi: 10.1016/j.prosdent.2019.12.005. [DOI] [PubMed] [Google Scholar]
- 39.Carvalho MA, Lazari PC, Gresnigt M, et al. Current options concerning the endodontically-treated teeth restoration with the adhesive approach. Braz Oral Res. 2018;32(Suppl 1):147–58. doi: 10.1590/1807-3107bor-2018.vol32.0074. [DOI] [PubMed] [Google Scholar]
- 40.Ferrini F, Paolone G, Di Domenico GL, et al. SEM evaluation of the marginal accuracy of zirconia, lithium disilicate, and composite single crowns created by CAD/CAM method: Comparative analysis of different materials. Materials (Basel) 2023;16(6):2413. doi: 10.3390/ma16062413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Turkyilmaz I, Benli M, Yun S. Evaluation of marginal and internal fit of lithium disilicate and zirconia all-ceramic CAD-CAM crowns using digital impressions: A systematic review. Prim Dent J. 2023;12(1):88–95. doi: 10.1177/20501684231154323. [DOI] [PubMed] [Google Scholar]
- 42.Shafi MA, Rayyan MR. Failure loads of heat-pressed versus milled lithium disilicate endocrowns. Clin Oral Investig. 2023;27(1):339–44. doi: 10.1007/s00784-022-04728-y. [DOI] [PubMed] [Google Scholar]
- 43.Ioannidis A, Park JM, Hüsler J, et al. An in vitro comparison of the marginal and internal adaptation of ultrathin occlusal veneers made of 3D-printed zirconia, milled zirconia, and heat-pressed lithium disilicate. J Prosthet Dent. 2022;128(4):709–15. doi: 10.1016/j.prosdent.2020.09.053. [DOI] [PubMed] [Google Scholar]
- 44.Riccitiello F, Amato M, Leone R, et al. In vitro evaluation of the marginal fit and internal adaptation of zirconia and lithium disilicate single crowns: Micro-CT comparison between different manufacturing procedures. Open Dent J. 2018;12:160–72. doi: 10.2174/1874210601812010160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Qamar Z, Alghamdi AMS, Haydarah NKB, et al. In vitro evaluation of lithium disilicate endocrowns and post and core crowns – a systematic review. J Funct Biomater. 2023;14(5):276. doi: 10.3390/jfb14050276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.Chouksey P, Yadav NS, Hazari P, et al. In vitro evaluation of marginal adaptation of polyether ether ketone and zirconia copings. Niger J Clin Pract. 2023;26:701–8. doi: 10.4103/njcp.njcp_701_22. [DOI] [PubMed] [Google Scholar]
- 47.GPT-9. The Glossary of Prosthodontic Terms: The Academy of Prosthodontics Foundation Editorial Staff Glossary of Prosthodontic Terms Committee of the Academy of Prosthodontics 9th Ed. J Prosthet Dent. 2017;117(5S):e1–e105. doi: 10.1016/j.prosdent.2016.12.001. [DOI] [PubMed] [Google Scholar]
- 48.Babu PJ, Alla RK, Alluri VR, et al. Dental ceramics: Part I – an overview of composition, structure and properties. Am J Mater Eng Technol. 2015;3:13–18. [Google Scholar]
- 49.Elashmawy Y, Aboushelib M, Elshahawy W. Retention of different CAD/CAM endocrowns bonded to severely damaged endodontically treated teeth: An in vitro study. J Indian Prosthodont Soc. 2021;21(3):269–75. doi: 10.4103/jips.jips_91_21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Vág J, Nagy Z, Bocklet C, et al. Marginal and internal fit of full ceramic crowns milled using CADCAM systems on cadaver full arch scans. BMC Oral Health. 2020;20(1):189. doi: 10.1186/s12903-020-01181-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Gold SA, Ferracane JL, da Costa J. Effect of crystallization firing on marginal gap of CAD/CAM fabricated lithium disilicate crowns. J Prosthodont. 2018;27(1):63–66. doi: 10.1111/jopr.12638. [DOI] [PubMed] [Google Scholar]
- 52.Oh KC, Park JM, Moon HS. Effects of scanning strategy and scanner type on the accuracy of intraoral scans: A new approach for assessing the accuracy of scanned data. J Prosthodont. 2020;29(6):518–23. doi: 10.1111/jopr.13158. [DOI] [PubMed] [Google Scholar]
- 53.Son K, Lee KB. Effect of finish line locations of tooth preparation on the accuracy of intraoral scanners. Int J Comput Dent. 2021;24(1):29–40. [PubMed] [Google Scholar]
- 54.Park JM. Comparative analysis on reproducibility among 5 intraoral scanners: Sectional analysis according to restoration type and preparation outline form. J Adv Prosthodont. 2016;8(5):354–62. doi: 10.4047/jap.2016.8.5.354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.Bosch G, Ender A, Mehl A. A 3-dimensional accuracy analysis of chairside CAD/CAM milling processes. J Prosthet Dent. 2014;112(6):1425–31. doi: 10.1016/j.prosdent.2014.05.012. [DOI] [PubMed] [Google Scholar]
- 56.Mostafavi AS, Allahyari S, Niakan S, Atri F. Effect of preparation design on marginal integrity and fracture resistance of endocrowns: A systematic review. Front Dent. 2022;19:37. doi: 10.18502/fid.v19i37.11250. [DOI] [PMC free article] [PubMed] [Google Scholar]