Enzyme-Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes.

Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme-responsive nanoparticles for the targeted delivery of an anti-inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently-labeled, dexamethasone-loaded peptide-polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub-periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles-treated rats, compared to control groups injected with free dexamethasone and non-responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme-responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.

Immunomodulatory fibrous hyaluronic acid-Fmoc-diphenylalanine-based hydrogel induces bone regeneration.

AIM: To investigate the potential of an ultrashort aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration. MATERIALS AND METHODS: Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm-diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate hydrogel or left unfilled. Eight weeks after implantation, histology and micro-computed tomography analyses were performed. Immunohistochemistry was performed in six rats to assess the hydrogel's immunomodulatory effect. RESULTS: A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46 KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone. CONCLUSIONS: FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration.

Stabilizing gelatin-based bioinks under physiological conditions by incorporation of ethylene-glycol-conjugated Fmoc-FF peptides.

Over the last decade, three-dimensional (3D) printing technologies have attracted the interest of researchers due to the possibility of fabricating tissue- and organ-like structures with similarities to the organ of interest. One of the most widely used materials for the fabrication of bioinks is gelatin (Gel) due to its excellent biocompatibility properties. However, in order to fabricate stable scaffolds under physiological conditions, the most common approach is to use gelatin methacrylate (GelMA) that allows the crosslinking and therefore the stabilization of the hydrogel through UV crosslinking. The crosslinking process can be harmful to cells thus decreasing total cell viability. To overcome the need for post-printing crosslinking, a new approach of bioink formulation was studied, incorporating the Fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) peptide into the Gel bioink. However, although Fmoc-FF possesses excellent mechanical properties, the lack of elasticity and viscosity makes it unsuitable for 3D-printing. Here, we demonstrate that covalent conjugation of two different ethylene glycol (EG) motifs to the Fmoc-FF peptide increases the hydrophilicity and elasticity properties, which are essential for 3D-printing. This new approach for bioink formulation avoids the need for any post-printing manufacturing processes, such as chemical or UV crosslinking.

Thixotropic Red Microalgae Sulfated Polysaccharide-Peptide Composite Hydrogels as Scaffolds for Tissue Engineering.

Sulfated polysaccharides of red marine microalgae have recently gained much attention for biomedical applications due to their anti-inflammatory and antioxidant properties. However, their low mechanical properties limit their use in tissue engineering. Herein, to enhance the mechanical properties of the sulfated polysaccharide produced by the red marine microalga, Porphyridium sp. (PS), it was integrated with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide hydrogelator. Transparent, stable hydrogels were formed when mixing the two components at a 1:1 ratio in three different concentrations. Electron microscopy showed that all hydrogels exhibited a nanofibrous structure, mimicking the extracellular matrix. Furthermore, the hydrogels were injectable, and tunable mechanical properties were obtained by changing the hydrogel concentration. The composite hydrogels allowed the sustained release of curcumin which was controlled by the change in the hydrogel concentration. Finally, the hydrogels supported MC3T3-E1 preosteoblasts viability and calcium deposition. The synergy between the sulfated polysaccharide, with its unique bioactivities, and FmocFF peptide, with its structural and mechanical properties, bears a promising potential for developing novel tunable scaffolds for tissue engineering that may allow cell differentiation into various lineages.

Dipeptide Nanostructure Assembly and Dynamics via in Situ Liquid-Phase Electron Microscopy.

In this paper, we report the in situ growth of FF nanotubes examined via liquid-cell transmission electron microscopy (LCTEM). This direct, high spatial, and temporal resolution imaging approach allowed us to observe the growth of peptide-based nanofibrillar structures through directional elongation. Furthermore, the radial growth profile of FF nanotubes through the addition of monomers perpendicular to the tube axis has been observed in real-time with sufficient resolution to directly observe the increase in diameter. Our study demonstrates that the kinetics, dynamics, structure formation, and assembly mechanism of these supramolecular assemblies can be directly monitored using LCTEM. The performance of the peptides and the assemblies they form can be verified and evaluated using post-mortem techniques including time-of-flight secondary ion mass spectrometry (ToF-SIMS).

Mechanical Enhancement and Kinetics Regulation of Fmoc-Diphenylalanine Hydrogels by Thioflavin†T.

The self-assembly of peptides is a key direction for fabrication of advanced materials. Novel approaches for fine tuning of macroscopic and microscopic properties of peptide self-assemblies are of a high demand for constructing biomaterials with desired properties. In this work, while studying the kinetics of the Fmoc-Diphenylalanine (Fmoc-FF) dipeptide self-assembly using the Thioflavin T (ThT) dye, we observed that the presence of ThT strongly modifies structural and mechanical properties of the Fmoc-FF hydrogel. Notably, the presence of ThT resulted in a tenfold increase of the gelation time and in the formation of short and dense fibers in the hydrogel. As a result of these morphological alteration higher thermal stability, and most important, tenfold increase of the hydrogel rigidity was achieved. Hence, ThT not only slowed the kinetics of the Fmoc-FF hydrogel formation, but also strongly enhanced its mechanical properties. In this study, we provide a detailed description of the ThT effect on the hydrogel properties and suggest the mechanisms for this phenomenon, paving the way for the novel approach to the control of the peptide hydrogels' micro- and macroscale properties.

Hyaluronic Acid and a Short Peptide Improve the Performance of a PCL Electrospun Fibrous Scaffold Designed for Bone Tissue Engineering Applications.

Bone tissue engineering is a rapidly developing, minimally invasive technique for regenerating lost bone with the aid of biomaterial scaffolds that mimic the structure and function of the extracellular matrix (ECM). Recently, scaffolds made of electrospun fibers have aroused interest due to their similarity to the ECM, and high porosity. Hyaluronic acid (HA) is an abundant component of the ECM and an attractive material for use in regenerative medicine; however, its processability by electrospinning is poor, and it must be used in combination with another polymer. Here, we used electrospinning to fabricate a composite scaffold with a core/shell morphology composed of polycaprolactone (PCL) polymer and HA and incorporating a short self-assembling peptide. The peptide includes the arginine-glycine-aspartic acid (RGD) motif and supports cellular attachment based on molecular recognition. Electron microscopy imaging demonstrated that the fibrous network of the scaffold resembles the ECM structure. In vitro biocompatibility assays revealed that MC3T3-E1 preosteoblasts adhered well to the scaffold and proliferated, with significant osteogenic differentiation and calcium mineralization. Our work emphasizes the potential of this multi-component approach by which electrospinning, molecular self-assembly, and molecular recognition motifs are combined, to generate a leading candidate to serve as a scaffold for bone tissue engineering.

Surface Modification by Nano-Structures Reduces Viable Bacterial Biofilm in Aerobic and Anaerobic Environments.

Bacterial biofilm formation on wet surfaces represents a significant problem in medicine and environmental sciences. One of the strategies to prevent or eliminate surface adhesion of organisms is surface modification and coating. However, the current coating technologies possess several drawbacks, including limited durability, low biocompatibility and high cost. Here, we present a simple antibacterial modification of titanium, mica and glass surfaces using self-assembling nano-structures. We have designed two different nano-structure coatings composed of fluorinated phenylalanine via the drop-cast coating technique. We investigated and characterized the modified surfaces by scanning electron microscopy, X-ray diffraction and wettability analyses. Exploiting the antimicrobial property of the nano-structures, we successfully hindered the viability of Streptococcus mutans and Enterococcus faecalis on the coated surfaces in both aerobic and anaerobic conditions. Notably, we found lower bacteria adherence to the coated surfaces and a reduction of 86-99% in the total metabolic activity of the bacteria. Our results emphasize the interplay between self-assembly and antimicrobial activity of small self-assembling molecules, thus highlighting a new approach of biofilm control for implementation in biomedicine and other fields.

Bio Mimicking of Extracellular Matrix.

Biomaterials play a critical role in regenerative strategies such as stem cell-based therapies and tissue engineering, aiming to replace, remodel, regenerate, or support damaged tissues and organs. The design of appropriate three-dimensional (3D) scaffolds is crucial for generating bio-inspired replacement tissues. These scaffolds are primarily composed of degradable or non-degradable biomaterials and can be employed as cells, growth factors, or drug carriers. Naturally derived and synthetic biomaterials have been widely used for these purposes, but the ideal biomaterial remains to be found. Researchers from diversified fields have attempted to design and fabricate novel biomaterials, aiming to find novel theranostic approaches for tissue engineering and regenerative medicine. Since no single biomaterial has been found to possess all the necessary characteristics for an ideal performance, over the years scientists have tried to develop composite biomaterials that complement and combine the beneficial properties of multiple materials into a superior matrix. Herein, we highlight the structural features and performance of various biomaterials and their application in regenerative medicine and for enhanced tissue engineering approaches.

Injectable Alginate-Peptide Composite Hydrogel as a Scaffold for Bone Tissue Regeneration.

The high demand for tissue engineering scaffolds capable of inducing bone regeneration using minimally invasive techniques prompts the need for the development of new biomaterials. Herein, we investigate the ability of Alginate incorporated with the fluorenylmethoxycarbonyl-diphenylalanine (FmocFF) peptide composite hydrogel to serve as a potential biomaterial for bone regeneration. We demonstrate that the incorporation of the self-assembling peptide, FmocFF, in sodium alginate leads to the production of a rigid, yet injectable, hydrogel without the addition of cross-linking agents. Scanning electron microscopy reveals a nanofibrous structure which mimics the natural bone extracellular matrix. The formed composite hydrogel exhibits thixotropic behavior and a high storage modulus of approximately 10 kPA, as observed in rheological measurements. The in vitro biocompatibility tests carried out with MC3T3-E1 preosteoblast cells demonstrate good cell viability and adhesion to the hydrogel fibers. This composite scaffold can induce osteogenic differentiation and facilitate calcium mineralization, as shown by Alizarin red staining, alkaline phosphatase activity and RT-PCR analysis. The high biocompatibility, excellent mechanical properties and similarity to the native extracellular matrix suggest the utilization of this hydrogel as a temporary three-dimensional cellular microenvironment promoting bone regeneration.

UV Light-Responsive Peptide-Based Supramolecular Hydrogel for Controlled Drug Delivery.

Low-molecular-weight self-assembled peptides may serve as promising hydrogelators for drug delivery applications by changing their structural network in response to external stimuli. Herein, inspired by the well-studied low-molecular-weight peptide hydrogelator, fluorenyl-methoxycarbonyl-diphenylalanine (Fmoc-FF), a novel peptide is designed and synthesized to include an ultraviolet (UV)-sensitive phototrigger. Similar to Fmoc-FF, 6-nitroveratryloxycarbonyl-diphenylalanine (Nvoc-FF) self-assembles to form a 3D, self-supporting, nanofibrous hydrogel. The Nvoc-FF hydrogel exhibits good mechanical properties with a storage modulus of 40 kPa. UV irradiation of the Nvoc-FF hydrogel encapsulating insulin-fluorescein isothiocyanate (insulin-FITC) results in the cleavage of Nvoc-FF peptide to produce unmasked FF, thereby facilitating the degradation of the hydrogel and the release of insulin-FITC. This release is in linear correlation to the irradiation time. In the present study, a first insight into this rigid, fibrous, light-responsive hydrogel is provided, allowing the fabrication of a novel drug delivery system for controlled release of large molecules.

Improving the Mechanical Rigidity of Hyaluronic Acid by Integration of a Supramolecular Peptide Matrix.

Hyaluronic acid (HA), a major component of the extracellular matrix, is an attractive material for various medical applications. Yet, its low mechanical rigidity and fast in vivo degradation hinder its utilization. Here, we demonstrate the reinforcement of HA by its integration with a low-molecular-weight peptide hydrogelator to produce a composite hydrogel. The formulation of HA with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide, one of the most studied self-assembling hydrogel-forming building blocks, showing notable mechanical properties, resulted in the formation of stable, homogeneous hydrogels. Electron microscopy analysis demonstrated a uniform distribution of the two matrices in the composite forms. The composite hydrogels showed improved mechanical properties and stability to enzymatic degradation while maintaining their biocompatibility. Moreover, the storage modulus of the FmocFF/HA composite hydrogels reached up to 25 kPa. The composite hydrogels allowed sustained release of curcumin, a hydrophobic polyphenol showing antioxidant, anti-inflammatory, and antitumor activities. Importantly, the rate of curcumin release was modulated as a function of the concentration of the FmocFF peptide within the hydrogel matrix. This work provides a new approach for conferring mechanical rigidity and stability to HA without the need of cross-linking, thus potentially facilitating its utilization in different clinical applications, such as sustained drug release.

Arginine-Presenting Peptide Hydrogels Decorated with Hydroxyapatite as Biomimetic Scaffolds for Bone Regeneration.

Hydrogels are promising candidates for biomimetic scaffolds of the extracellular matrix in tissue engineering applications. However, their use in bone tissue engineering is limited due to their low mechanical properties. In this study, we designed and synthesized multicomponent peptide-based hydrogels composed of fluorenyl-9-methoxycarbonyl diphenylalanine (FmocFF), which contributed to the rigidity and stability of the hydrogel, and Fmoc-arginine (FmocR), which mediated high affinity to hydroxyapatite (HAP) due to the arginine moiety. The new hydrogels composed of nanometric fibril networks were decorated with HAP and demonstrated high mechanical strength with a storage modulus of up to 29 kPa. In addition, the hydrogels supported cell adhesion and in vitro cell viability. These properties suggest using these multicomponent organic-inorganic hydrogels as functional biomaterials for improved bone regeneration.

Molecular co-assembly as a strategy for synergistic improvement of the mechanical properties of hydrogels.

Molecular self-assembly is a key direction for the fabrication of advanced materials. Yet, the physical properties of the formed assemblies are limited by the inherent characteristics of the specific building blocks. Here, we have applied a co-assembly approach to synergistically modulate the mechanical properties of peptide hydrogels, thereby forming extremely stable and rigid hydrogels.

Dimensional changes of the maxillary sinus following tooth extraction in the posterior maxilla with and without socket preservation.

BACKGROUND: Sinus pneumatization is commonly observed following tooth extraction in the posterior maxilla, however, the role of this pneumatization in the overall changes in the vertical bone height is not clear. PURPOSE: To compare dimensional changes in the alveolar ridge and corresponding maxillary sinus following tooth extraction, with or without socket preservation. MATERIALS AND METHODS: 42 patients underwent tooth extraction (control group) and 21 patients underwent tooth extraction with socket preservation using DBBM (study group). Panoramic radiographs, prior to and approximately 1 year post extractions were superimposed and matched using a fixed reference unit. The following measurements were performed in the midline of the tooth site: distance of the bone crest to the sinus floor; distance of the sinus floor to the sinus roof and the sagittal circumference of the maxillary. RESULTS: The mean change in the distance from the sinus floor to the sinus roof pre and post operatively was 0.30 mm (±0.10 SE) in the study group and 1.30 mm (±0.27 SE) in the control group (P = .0221). The mean change in the distance from the bone crest to the sinus floor was 0.32 mm (±0.09 SE) in the study group and 1.26 mm (±0.28 SE) in the control group (P = .0019), and the mean change in the sinus sagittal circumference was 37.34 mm (±6.10 SE) and 125.95 mm (±15.60 SE), respectively (P = .0001). CONCLUSIONS: Ridge preservation using bovine derived xenograft might reduce sinus pneumatization along with minimizing crestal bone resorption.

The Pathogenesis of Implant-Related Reactive Lesions: A Clinical, Histologic and Polarized Light Microscopy Study.

BACKGROUND: Peri-implant soft tissue reactive lesions (I-RLs) may jeopardize implant success and survival. To the best of the authors' knowledge, its pathogenesis is unknown. The objective of this study is to conduct a clinicopathologic and polarized light microscopy (PLM) analysis of 14 new I-RLs and compare them with comparable tooth-associated cases (T-RLs) to better understand I-RL pathogenesis. METHODS: Fifty-eight new cases of I-RL and T-RL were retrieved from the pathology department archives of Rambam Health Care Campus, Haifa, Israel. Retrospective analysis of histopathologic and clinical features was conducted, documented, and then compared for: 1) I-RL (n = 14), 2) peri-implant pyogenic granuloma (I-PG) (n = 5), 3) peri-implant peripheral giant cell granuloma (I-PGCG) (n = 9), 4) T-RL (n = 44), 5) tooth-associated pyogenic granuloma (T-PG) (n = 21), and 6) tooth-associated peripheral giant cell granuloma (T-PGCG) (n = 23). Presence of foreign bodies was assessed using PLM. RESULTS: Foreign bodies were found more commonly in I-RLs (n = 13/14; 93%) when compared with T-RLs (n = 18/44; 41%), which was a statistically significant difference (P = 0.01) with an odds ratio of 7.9. Microscopically, I-PGCG was associated with: 1) lower multinucleated giant cell count (P = 0.04); 2) lower density of mesenchymal cells (P = 0.05); and 3) more diffuse, non-lobulated stromal morphology (P = 0.001). Clinically, I-RLs were found in patients who were older, and all cases were located in the posterior region: mandible (n = 12/14; 86%) and maxilla (n = 2/14; 14%). CONCLUSIONS: In cases of implant failure, implantation of foreign bodies may play a role with subsequent development of I-PG and I-PGCG-like lesions. Clinicians should be aware of this risk so they can implement measures to minimize adverse implant outcomes.

The association between shallow vestibular depth and peri-implant parameters: a retrospective 6 years longitudinal study.

AIM: The aim of this study was to retrospectively evaluate the association between shallow vestibular depth (VD) and peri-implant parameters. MATERIAL AND METHODS: Peri-implant parameters were evaluated in 61 periodontal patients under regular supportive periodontal therapy. Clinical parameters included gingival index (GI), plaque index (PI), bleeding on probing (BOP), peri-implant pocket depths (PPD), mucosal recession (MR), relative attachment level (RAL), width and thickness of keratinized mucosa (KMW, KMT) and VD. Radiographic bone level (RBL) was measured on peri-apical radiographs. RESULTS: Sites with shallow VD (≤ 4 mm) were associated with higher MR (0.91 mm versus 0.47 mm, p ≤ 0.009), higher RAL (4.23 mm versus 3.59 mm, p ≤ 0.0001) and higher RBL (2.18 mm versus 1.7 mm, p = 0.05) when compared with adequate vestibular depth sites (VD > 4 mm). Moreover, sites with shallow VD presented lower KMW compared with sites with adequate VD (1.24 mm versus 2.38 mm, respectively, p ≤ 0.0001). Slightly greater BOP, and GI were recorded for the shallow VD compared with adequate sites. According to multivariate analysis, factors that could predict RAL included: VD, GI, age, supporting periodontal therapy, implant type and design. CONCLUSIONS: Based on this study, inadequate vestibular depth around dental implants may be associated with increased peri-implant bone loss and mucosal recession. Further prospective and intervention studies will be required to fully understand this phenomenon.

The association between dental proximal restorations and periodontal disease: A retrospective 10-18 years longitudinal study.

OBJECTIVE: Dental restorations may be plaque retentive. The aim of this study was to evaluate the long-term association between proximal restorations and the incidence and progression of periodontal disease in well-maintained patients. METHOD AND MATERIALS: Probing pocket depths (PPD), bleeding on probing (BOP), and radiographic status of proximal restorations were retrospectively retrieved from files of patients attending a specialist periodontal office. Ill-fitting margins were recorded. The association between these parameters was evaluated at baseline examination (T0), after cause-related therapy (T1) and after ≥ 10 years from T0 (T2), during which supportive periodontal therapy (SPT) was administered, using descriptive statistics, ANOVA-Bonferroni, and chi-square analyses. RESULTS: 1,301 teeth were examined. Mean PPD in unrestored surfaces was 3.7 ± 1.7 mm, 3.1 ± 1.3 mm, and 2.8 ± 1 mm at T0, T1, and T2, respectively. Deeper pockets were found in restored surfaces at those time points with PPD values of 4.4 ± 1.8 mm, 3.6 ± 1.4 mm, and 3.2 ± 1.1 mm, respectively (P < .001). Higher PPD values were found in restored surfaces exhibiting inadequate restorations when compared to restored surfaces with adequate restorations at all time points. These values were 4.9 ± 1.9 mm, 4.1 ± 1.5 mm, and 4 ± 1.7 mm vs 4.3 ± 1.8 mm, 3.6 ± 1.4 mm, and 3.1 ± 1.1 mm, respectively (P < .001). CONCLUSION: The present study confirmed that restorations might be detrimental to periodontal health. A significant association between the presence of proximal restorations and the incidence of periodontal disease was observed. This association was more pronounced for inadequate restorations while becoming less significant over time in patients receiving routine SPT.

Variables affecting tooth survival and changes in probing depth: a long-term follow-up of periodontitis patients.

AIM: To retrospectively assess tooth-survival rate and its association with patient and oral variables in periodontal office patients, followed up to 18 years. MATERIAL AND METHODS: Patients in a private periodontal office whose files included initial examination (T0 ), reevaluation (TRe ) and ≥ 10 years after T0 (TF ) chartings, and received periodontal therapy and supportive periodontal therapy (SPT) after TRe were included. General health, plaque scores (PI), probing depth (PPD), bleeding on probing (BOP) at six points/tooth, tooth extractions, and SPT visits were extracted from patient files at T0 , TRe , and TF . Descriptive statistics and Cox regression analysis were performed. RESULTS: Fifty patients (mean 26 ± 4 teeth/patient, 1301 teeth) fulfilled inclusion criteria. About 20 and 129 teeth respectively were extracted before/after TRe , 96 of them for periodontal causes. PPD>7 mm at TRe (HR = 17.7, 95%CI 8.6, 36.6), age above 60 years (HR = 3.3, 95%CI 1.5, 7.2), multi-rooted teeth (HR = 1.9, 95%CI 1.2, 3.1) and SPT<3 times/year (HR = 1.8, 95%CI 1.1, 2.9), were the best prognostic factors for tooth loss during follow-up. (p < 0.05, Cox regression analysis). A continuous, statistically significant reduction was observed in mean PPD among teeth that survived follow-up [4.3 ± 1.8 mm, 3.5 ± 1.4 mm, 3.2 ± 1.3 mm, at T0 , TRe , TF , respectively. (p < 0.001, Repeated-measures test)]. CONCLUSION: Regular SPT was associated with low tooth-loss rates and continuous reductions in probing depth. PPD after initial therapy, age above 60, multi-rooted teeth and infrequent SPT were strong negative prognostic factors for long-term tooth survival among periodontal patients.

Diagnostic accuracy of cone beam computed tomography for dimensional linear measurements in the mandible.

PURPOSE: To compare linear measurements made on cone beam computed tomography (CBCT) images to direct measurements in ex vivo porcine mandibles. MATERIALS AND METHODS: Six cross-sectional planes were defined by gutta-percha-filled cavities in seven mandibles. The mandibles were scanned in a CBCT apparatus and later sectioned, using a band saw, through the gutta-percha markers. Next, four direct (DIR) linear measurements were performed for each section with a handheld digital caliper, using the gutta-percha markers as reference points. The corresponding radiographic (RAD) cross sections were then measured using dedicated software. A total of 168 sites were measured. Differences between RAD and DIR measurements [Δ (RAD - DIR)] were calculated for each pair individually. RESULTS: Mean Δ (RAD - DIR) was -0.17 ± 0.53 mm (range, -1.42 to 1.09 mm). CBCT overestimated direct measurements at 36% of the sites; 8% of sites (95% confidence interval, 3.8% to 12.2%) showed errors between +0.5 and +1 mm, and 1.8% (95% confidence interval, -0.2% to 3.9%) showed errors greater than +1 mm. CONCLUSIONS: Good correlation was found between CBCT and direct measurements. However, the significant percentage of sites with overestimation of at least 0.5 mm indicates a need for safety margins to be maintained when CBCT is used to plan surgical interventions such as dental implant therapy.