Accuracy of zirconia crown manufactured using stereolithography and digital light processing.

OBJECTIVES: The aim of this study is to evaluate the accuracy of zirconia crowns fabricated using stereolithography (SLA) and digital light processing (DLP) and to compare their accuracy with those fabricated using the subtractive manufacturing (SM) method. METHODS: A typodont model with a prepared maxillary first molar was scanned, and the anatomical contour crown was designed using dental computer-aided-design (CAD) software. The designed file in standard tessellation language (STL) format was used to fabricate 10 crowns per group. The crowns were manufactured using a dental milling machine (Datron D5; MLC group), SLA (CERAMAKER 900; SLAC group), and DLP (ZIPRO; DLPC group) printers. The fabricated crowns were scanned using a dental laboratory scanner and saved in three parts: the external, intaglio, and marginal surfaces. For accuracy assessment, these parts were superimposed to the reference file. Root mean square (RMS) values were evaluated using three-dimensional analysis software (Geomagic Control X). Statistical significance was evaluated using a nonparametric Kruskal-Wallis test (α = 0.05) and a post-hoc Mann-Whitney U test with Bonferroni correction (α = 0.016). RESULTS: Trueness evaluation revealed the lowest RMS value in all areas in the MLC group, followed by that in the DLPC group. The precision evaluation revealed the lowest RMS value in all areas in the MLC group. Statistically significant differences were observed among the groups in the external, intaglio, and marginal surface (P < 0.05). CONCLUSIONS: Although the restorations fabricated using SM revealed higher accuracy, the crowns manufactured using SLA and DLP methods were considered clinically acceptable. CLINICAL SIGNIFICANCE: In the production of zirconia crowns, subtractive manufacturing continues to demonstrate significantly higher accuracy compared to additive manufacturing. However, crowns fabricated using the additive manufacturing method also demonstrated high accuracy.

Highly Efficient Ultra-Thin EML Blue PHOLEDs with an External Light-Extraction Diffuser.

In this study, various diffusers are applied to highly efficient ultra-thin emission layer (EML) structure-based blue phosphorescent organic light-emitting diodes (PHOLEDs) to improve the electroluminescence (EL) characteristics and viewing angle. To achieve highly efficient blue PHOLEDs, the EL characteristics of ultra-thin EML PHOLEDs with the various diffusers having different structures of pattern-shape (hemisphere/sphere), size (4~75 µm), distribution (surface/embedded), and packing (close-packed/random) were systematically analyzed. The diffusers showed different enhancements in the overall EL characteristics of efficiencies, viewing angle, and others. The EL characteristics showed apparent dependency on their structure. The external quantum efficiency (EQE) was enhanced mainly by following the orders of pattern, size, and shape. Following the pattern size, the EQE enhancement gradually increased; the largest-sized diffuser with a 75 µm closed-packed hemisphere (diffuser-1) showed a 1.47-fold EQE improvement, which was the highest. Meanwhile, the diffuser with a ~7 µm random embedded sphere with a low density (diffuser 5) showed the lowest 1.02-fold-improved EQE. The reference device with ultra-thin EML structure-based blue PHOLEDs showed a maximum EQE of 16.6%, and the device with diffuser 1 achieved a maximum EQE of 24.3% with a 5.1% wider viewing angle compared to the reference device without a diffuser. For the in-depth analysis, the viewing angle profile of the ultra-thin EML PHOLED device and fluorescent green OLEDs were compared. As a result, the efficiency enhancement characteristics of the diffusers show a difference in the viewing angle profile. Finally, the application of the diffuser successfully demonstrated that the EL efficiency and viewing angle could be selectively improved. Additionally, we found that it was possible to realize a wide viewing angle and achieve considerable EQE enhancement by further investigations using high-density and large-sized embedded structures of light-extraction film.

Doping-Free Phosphorescent and Thermally Activated Delayed Fluorescent Organic Light-Emitting Diodes with an Ultra-Thin Emission Layer.

We report the electroluminescence (EL) characteristics of blue ultra-thin emissive layer (U-EML) phosphorescent (PH) organic light-emitting diodes (OLED) and thermally activated delayed fluorescence (TADF) OLED. A variety of transport layer (TL) materials were used in the fabricated OLEDs. The well-known FIrpic and DMAC-DPS were used with a thickness of 0.3 nm, which is relatively thicker than the optimal thickness (0.15 nm) of the blue phosphorescent ultra-thin emissive layer to ensure sufficient energy transfer. While FIrpic showed overall high efficiency in various TLs, DMAC-DPS exhibited three times lower efficiency in limited TLs. To clarify/identify low efficiency and to improve the EL, the thickness of DMAC-DPS was varied. A significantly higher and comparable efficiency was observed with a thickness of 4.5 nm, which is 15 times thicker. This thickness was oriented from the TADF itself, which reduces quenching in a triplet-triplet annihilation compared to the PH process. The thinner optimal thickness compared with ~30 nm of fluorescent OLEDs suggests that there still is quenching taking place. We expect that the efficiency of TADF U-EML OLEDs can be enhanced through further research on controlling the exciton quenching using multiple U-EMLs with spacers and a novel material with a high energy transfer rate (ΔES-T).

Fabrication of Flexible PDMS Films with Micro-Convex Structure for Light Extraction from Organic Light-Emitting Diodes.

In this study, we demonstrated organic light-emitting diodes (OLEDs) outcoupling with a flexible polydimethylsiloxane (PDMS) film with a micro-convex structure using the breath figure (BF) method. We can easily control the micro-convex pattern by adjusting the concentration of polystyrene and the humidity during the BF process. As process conditions to fabricate the micro-convex structure, polymer concentrations of 10, 20, 40, and 80 mg/mL and 60, 70, and 80% relative humidity were used. To evaluate the optical properties, we analyzed the transmission, diffusion, and electroluminescence with or without the micro-convex structure on the OLEDs. The shape and density of the micro-convex structure are related to its optical properties and outcoupling and we have experimentally demonstrated this. By applying a micro-convex structure, it achieved up to a 42% improvement in the external quantum efficiency compared to bare OLEDs (without any light extraction film). We expect the fabricated flexible light extraction film to be effective for outcoupling and applicable to flexible devices.

Enhancing Light Extraction Efficiency in OLED Using Scattering Structure-Embedded DMD-Based Transparent Composite Electrodes.

This study investigates the application of scattering structures to the metal layer in a DMD (Dielectric/Metal/Dielectric) configuration through plasma treatment. The purpose is to enhance the light extraction efficiency of organic light-emitting diodes (OLEDs). Different plasma conditions were explored to create scattering structures on the metal layer. The fabricated devices were characterized for their electrical and optical properties. The results demonstrate that the introduction of scattering structures through plasma treatment effectively improves the light extraction efficiency of OLEDs. Specifically, using O2-plasma treatment on the metal layer resulted in significant enhancements in the total transmittance, haze, and figure of merit. These findings suggest that incorporating scattering structures within the DMD configuration can effectively promote light extraction in OLEDs, leading to enhanced overall performance and light efficiency.

Evaluation of internal fit of press ceramic and porous structured cobalt-chromium crown fabricated by additive manufacturing.

Background: The purpose of this in vitro study is to fabricate a novel metal-ceramic prosthesis with a porous structure, to compensate for the disadvantages associated with the design of existing prostheses, and to measure the internal fit of this prosthesis. Materials and Methods: In this in vitro study, the mandibular first molar was scanned from the dental computer-aided-design to design a 3 mm porous structure frame. The frame was produced using the lamination method and fired in a pressed ceramic. For comparison, pore-free specimens were fabricated by selective laser sintering (SLS) as described above, and porous specimens were fabricated by casting (total n = 30). The internal fit was then measured using a digital microscope (at 100× magnification), and the data were analyzed using one-way ANOVA (α = 0.05). Results: The total mean internal discrepancies for each group were 42.32 ± 22.50 µm for the porous structure SLS group (PS-group), 107.54 ± 38.75 µm for no-porous casting group (group), and 121.36 ± 50.19 µm for the no-porous SLS group (group), with significant differences (P < 0.05) among all groups. Conclusion: The internal discrepancies of porous structure crown fabricated by SLS were smaller than that of no-porous crown fabricated by casting and SLS. Based on these laboratory findings, further studies should be conducted to evaluate the feasibility of the newly designed porous structure and press ceramic prosthesis to determine whether they can be applied in clinical practice.

Micro-Sphere PDMS for Enhancing Light Extraction in Organic Light-Emitting Devices.

We present a micro-sphere PDMS film to improve the external quantum efficiency (EQE) in OLEDs. The micro-sphere PDMS film was fabricated with the breath figure (BF) and replica molding process. The polymer template was prepared through stabilization of the water droplets at the polymer/water interface. The micro-sphere PDMS film was fabricated by pouring PDMS on the polymer template. At a 45 mg/mL concentration, the size of the spheres was approximately 12.3 µm and they had the most circular shape, so this condition yielded the best performance, with an improvement of 33% in the EQE and the widest viewing angle ranging from 0° to 50°. As a result, the sphere film's size and distribution seem to play important roles in enhancing the EQE in OLEDs. Furthermore, the flexible sphere film based on polymeric materials could offer an effective, large-scale, mass-produced product and a simple process and approach to achieve high efficiency in flexible OLEDs.

A Simple Method for Fabricating an External Light Extraction Composite Layer with RNS to Improve the Optical Properties of OLEDs.

In this study, we fabricated a random nanostructure (RNS) external light extraction composite layer containing high-refractive-index nanoparticles through a simple and inexpensive solution process and a low-temperature mask-free process. We focused on varying the shape and density of the RNSs and adjusted the concentration of the high-refractive-index nanoparticles to control the optical properties. The RNSs fabricated using a low-temperature mask-free process can use the distance between the nanostructures and various forms to control the diffraction and scattering effects in the visible light wavelength range. Consequently, our film exhibited a direct transmittance of ~85% at a wavelength of 550 nm. Furthermore, when the RNSs' composite film, manufactured using the low-temperature mask-free process, was applied to organic light-emitting diodes (OLEDs), it exhibited an external quantum efficiency improvement of 32.2% compared with the OLEDs without the RNSs. Therefore, the randomly distributed high-refractive-index nanoparticles on the polymer film can reduce the waveguide mode and total reflection at the substrate/air interface. These films can be used as a scattering layer to reduce the loss of the OLED substrate mode.

Enhanced Light Extraction from Organic Light-Emitting Diodes with Micro-Nano Hybrid Structure.

In this study, an external light extraction layer with a micro-nano hybrid structure was applied to improve the external light extraction efficiency of organic light-emitting diodes (OLEDs). A reactive ion-etching (RIE) process, using O2 and CHF3 plasma, was performed on the surface of the micro-scale pattern to form micro-nano hybrid structures. According to the results of this study, the nanostructures formed by the treatment of O2 and CHF3 were different, and the efficiency according to the structures was analyzed experimentally and theoretically. As a result, the OLED, to which the micro-nano hybrid structure, manufactured through a simple process, is applied, improved the external light extraction efficiency by up to 38%, and an extended viewing angle profile was obtained. Additionally, an effective method for enhancing the out-coupling efficiency of OLEDs was presented by optimizing the micro-nano hybrid structure according to process conditions.

Quantitative and qualitative evaluation on the accuracy of three intraoral scanners for human identification in forensic odontology.

The purpose of this study was to analyze the accuracy of intra oral scanner (IOS) to confirm the applicability of IOS for the recording and analysis of tooth morphology in forensics. The less damaged mandible specimen with many teeth remaining was scanned three times using three types of intraoral scanners (CS3600, i500, and Trios3). For quantitative comparisons of the scanned images produced by these intraoral scanners, root mean square (RMS) values were computed using a three-dimensional analysis program and a one-way ANOVA was conducted with Tukey HSD (honestly significant difference) as a post-hoc analysis (α=0.05). The repeatability of the full scan data was highest with the i500 (0.14±0.03 mm), and the post-hoc analysis confirmed significant differences between the CS3600 and the i500 outcomes (P-value=0.003). The repeatability of the partial scan data for the teeth in the mandible was highest with the i500 (0.08±0.02 mm), and the post-hoc analysis confirmed significant differences between the CS3600 and the i500 (P-value=0.016). The precision of the full scan data was highest with the i500 (0.16±0.01 mm) but the differences were not statistically significant (P-value=0.091). Meanwhile, the precision of the partial scan data for the teeth in the mandible was highest with the Trios3 (0.22±0.02 mm), but the differences were not statistically significant (P-value=0.762). Considering that the scanning of other areas of the oral cavity in addition to the teeth is important in forensic odontology, the i500 scanner appears to be the most appropriate intraoral scanner for human identification. However, as the scope of oral scanning is generally limited to teeth in the practice of dentistry, additional discussions of how to apply the IOS in forensic odontology are needed. Ultimately, the results here can contribute to the overall discussion of the forensic applicability dental data produced by intraoral scanners.

Radiofrequency therapy improves exercise capacity of mice with emphysema.

Emphysema is a common phenotype of chronic obstructive pulmonary disease (COPD). Although resection of emphysematous tissue can improve lung mechanics, it is invasive and fraught with adverse effects. Meanwhile, radiofrequency (RF) treatment is an extracorporeal method that leads to tissue destruction and remodeling, resulting in "volume reduction" and overall improvement in lung compliance of emphysematous lungs. Whether these changes lead to improved exercise tolerance is unknown. Here, we investigated the effectiveness of RF treatment to improve the exercise capacity of mice with emphysema. Fifty-two mice (7 weeks of age) were used in this experiment. A bilateral emphysema model was created by intratracheally instilling porcine pancreatic elastase (PPE) (1.5U/100 g body weight). RF treatment (0.5 W/ g body weight) was administered extracorporeally 14 days later and mice were sacrificed after another 21 days. The exercise capacity of mice was measured using a treadmill. Treadmill runs were performed just before PPE instillation (baseline), before RF treatment and before sacrifice. Following sacrifice, lung compliance and mean linear intercept (Lm) were measured and fibrosis was assessed using a modified Ashcroft score. There were 3 experimental groups: controls (instilled with saline, n = 12), emphysema (instilled with porcine pancreatic elastase, PPE, n = 11) and emphysema + treatment (instilled with PPE and given RF, n = 9). At endpoint, the maximum velocity of the emphysema + treatment group was significantly higher than that of the emphysema group, indicating improved exercise tolerance (86.29% of baseline vs 61.69% of baseline, p = 0.01). Histological analysis revealed a significant reduction in emphysema as denoted by Lm between the two groups (median 29.60 µm vs 35.68 µm, p = 0.03). The emphysema + treatment group also demonstrated a higher prevalence of lung fibrosis (≧Grade 3) compared with the emphysema group (11.7% vs 5.4%, p < 0.01). No severe adverse events from RF were observed. RF treatment improved the exercise capacity of mice with emphysema. These data highlight the therapeutic potential of RF treatment in improving the functional status of patients with COPD.

Cannabis Glandular Trichome Cell Walls Undergo Remodeling to Store Specialized Metabolites.

The valuable cannabinoid and terpenoid metabolites of Cannabis sativa L. are produced by floral glandular trichomes. The trichomes consist of secretory disk cells, which produce the abundant lipidic metabolites, and an extracellular storage cavity. The mechanisms of apoplastic cavity formation to accumulate and store metabolites in cannabis glandular trichomes remain wholly unexplored. Here, we identify key wall components and how they change during cannabis trichome development. While glycome and monosaccharide analyses revealed that glandular trichomes have loosely bound xyloglucans and pectic polysaccharides, quantitative immunolabeling with wall-directed antibodies revealed precise spatiotemporal distributions of cell wall epitopes. An epidermal-like identity of early trichome walls matured into specialized wall domains over development. Cavity biogenesis was marked by separation of the subcuticular wall from the underlying surface wall in a homogalacturonan and α-1,5 arabinan epitope-rich zone and was associated with a reduction in fucosylated xyloglucan epitopes. As the cavity filled, a matrix with arabinogalactan and α-1,5 arabinan epitopes enclosed the metabolite droplets. At maturity, the disk cells' apical wall facing the storage cavity accumulated rhamnogalacturonan-I epitopes near the plasma membrane. Together, these data indicate that cannabis glandular trichomes undergo spatiotemporal remodeling at specific wall subdomains to facilitate storage cavity formation and metabolite storage.

Characteristics of Self-Nanostructured Growth of 4,6-Bis(3,5-di(pyridin-3-yl)phenyl)-2-Methylpyrimidine (B3PyMPM).

In this study, we report the self-nanostructured growth of 4,6-bis(3,5-di(pyridin-3-yl)phenyl)-2-methylpyrimidine (B3PyMPM), which is widely used as an electron transport layer for organic light-emitting diodes (OLEDs). B3PyMPM nanostructures were formed on the surface of a substrate using vacuum thermal evaporation, and parameters such as substrate rotation speed and evaporation angle were altered to study their effect on the growth of nanostructures. Moreover, it was proven that the growth of nanostructures was dependent on the underneath materials. This self-nanostructured growth of B3PyMPM would affect the outcoupling and the efficiency improvement of OLEDs.

Evaluation of bond strength of porous cobalt-chromium metal and pressed ceramic fabricated by additive manufacturing.

STATEMENT OF PROBLEM: A high metal-ceramic bond strength is important for successful dental restorations. However, studies on the evaluation of the bond strength of porous metal-ceramic restorations compared with conventional ones are scarce. PURPOSE: The purpose of this in vitro study was to compare the bond strength of a porous metal-ceramic structure with conventional metal-ceramic restorations. MATERIAL AND METHODS: Ten porous specimens were fabricated by selective laser sintering (SLS) according to the International Organization for Standardization 9693-1:2012, 10 specimens without porosity by SLS, and 10 cobalt-chromium (Co-Cr) cast specimens without porosity. The ceramic was applied with the pressing method. A 3-point bend test was performed with a universal testing machine, and the data were statistically analyzed by using 1-way analysis of variance (α=.05). RESULTS: The mean ±standard deviation bond strength of the porous group fabricated by SLS was the lowest (35.6 ±9.1 MPa), that of the group without porosity in the casting method was 43.5 ±7.8 MPa, and that of the group without porosity fabricated by SLS was the highest (47.7 ±4.5 MPa); these were statistically similar (P=.058). CONCLUSIONS: Although the porous structure reported the lowest bond strength among the 3 sets of test specimens, its bond strength was higher than the International Standards Organization standard of 25 MPa.

Comparison of stress distribution in dental crown with different cusp angles: 3D finite element analysis.

The purpose of this study is to measure the failure risk of a crown depending on the cusp angle. Three all-ceramic crown models consisting of CH (high incline), CM (middle incline), and CL (low incline) are designed. Stress is applied to the crown with Loading case-1 (top of cusp tip) and Loading case-2 (middle of cusp ridge) with the use of FEA software. In Loading case-1 and case-2, the CH showed the highest Maximum Principal Stress (MPS) while the CL showed the lowest MPS. The cusp angle is an influential factor affecting stress distribution in dental crowns.

A study on the machining accuracy of dental digital method focusing on dental inlay.

PURPOSE: The purpose of this study was to compare the cutting method and the lamination method to investigate whether the CAD data of the proposed inlay shape are machined correctly. MATERIALS AND METHODS: The Mesial-Occlusal shape of the inlay was modeled by changing the stereolithography (STL). Each group used SLS (metal powder) or SLA (photocurable resin) in the additive method, and wax or zirconia in the subtractive method (n=10 per group, total n=40). Three-dimensional (3D) analysis program (Geomagic Control X inspection software; 3D systems) was used for the alignment and analysis. The root mean square (RMS) in the 2D plane state was measured within 50 µm radius of eight comparison measuring points (CMP). Differences were analyzed using one-way analysis of variance and post-hoc Tukey's test were used (α=.05). RESULTS: There was a significant difference in RMS only in SLA and SLS of 2D section (P<.05). In CMP mean, CMP 4 (-5.3±46.7 µm) had a value closest to 0, while CMP 6 (20.1±42.4 µm) and CMP 1 (-89.2±61.4 µm) had the greatest positive value and the greatest negative value, respectively. CONCLUSION: Since the errors obtained from the study do not exceed the clinically acceptable values, the lamination method and the cutting method can be used clinically.

A comparative study of additive and subtractive manufacturing for dental restorations.

STATEMENT OF PROBLEM: Digital systems have recently found widespread application in the fabrication of dental restorations. For the clinical assessment of dental restorations fabricated digitally, it is necessary to evaluate their accuracy. However, studies of the accuracy of inlay restorations fabricated with additive manufacturing are lacking. PURPOSE: The purpose of this in vitro study was to evaluate and compare the accuracy of inlay restorations fabricated by using recently introduced additive manufacturing with the accuracy of subtractive methods. MATERIAL AND METHODS: The inlay (distal occlusal cavity) shape was fabricated using 3-dimensional image (reference data) software. Specimens were fabricated using 4 different methods (each n=10, total N=40), including 2 additive manufacturing methods, stereolithography apparatus and selective laser sintering; and 2 subtractive methods, wax and zirconia milling. Fabricated specimens were scanned using a dental scanner and then compared by overlapping reference data. The results were statistically analyzed using a 1-way analysis of variance (α=.05). Additionally, the surface morphology of 1 randomly (the first of each specimen) selected specimen from each group was evaluated using a digital microscope. RESULTS: The results of the overlap analysis of the dental restorations indicated that the root mean square (RMS) deviation observed in the restorations fabricated using the additive manufacturing methods were significantly different from those fabricated using the subtractive methods (P<.05). However, no significant differences were found between restorations fabricated using stereolithography apparatus and selective laser sintering, the additive manufacturing methods (P=.466). Similarly, no significant differences were found between wax and zirconia, the subtractive methods (P=.986). The observed RMS values were 106 µm for stereolithography apparatus, 113 µm for selective laser sintering, 116 µm for wax, and 119 µm for zirconia. Microscopic evaluation of the surface revealed a fine linear gap between the layers of restorations fabricated using stereolithography apparatus and a grooved hole with inconsistent weak scratches when fabricated using selective laser sintering. In the wax and zirconia restorations, possible traces of milling bur passes were observed. CONCLUSIONS: The results indicate that the accuracy of dental restorations fabricated using the additive manufacturing methods is higher than that of subtractive methods. Therefore, additive manufacturing methods are a viable alternative to subtractive methods.

In vitro evaluation of the bond strength between various ceramics and cobalt-chromium alloy fabricated by selective laser sintering.

PURPOSE: This study aimed to present the clinical applicability of restorations fabricated by a new method, by comparing the bond strength of between ceramic powder with different coefficient of thermal expansion and alloys fabricated by Selective laser sintering (SLS). MATERIALS AND METHODS: Fifty Co-Cr alloy specimens (25.0 × 3.0 × 0.5 mm) were prepared by SLS and fired with the ceramic (8.0 × 3.0 × 0.5 mm) (ISO 9693:1999). For comparison, ceramics with different coefficient of thermal expansion were used. The bond strength was measured by three-point bending testing and surfaces were observed with FE-SEM. Results were analyzed with a one-way ANOVA (α=.05). RESULTS: The mean values of Duceram Kiss (61.18 ± 6.86 MPa), Vita VM13 (60.30 ± 7.14 MPa), Ceramco 3 (58.87 ± 5.33 MPa), Noritake EX-3 (55.86 ± 7.53 MPa), and Vintage MP (55.15 ± 7.53 MPa) were found. No significant difference was observed between the bond strengths of the various metal-ceramics. The surfaces of the specimens possessed minute gaps between the additive manufactured layers. CONCLUSION: All the five powders have bond strengths higher than the required 25 MPa minimum (ISO 9693); therefore, various powders can be applied to metal structures fabricated by SLS.

Bond and fracture strength of metal-ceramic restorations formed by selective laser sintering.

PURPOSE: The purpose of this study was to compare the fracture strength of the metal and the bond strength in metal-ceramic restorations produced by selective laser sintering (SLS) and by conventional casting (CAST). MATERIALS AND METHODS: Non-precious alloy (StarLoy C, DeguDent, Hanau, Germany) was used in CAST group and metal powder (SP2, EOS GmbH, Munich, Germany) in SLS group. Metal specimens in the form of sheets (25.0 × 3.0 × 0.5 mm) were produced in accordance with ISO 9693:1999 standards (n=30). To measure the bond strength, ceramic was fired on a metal specimen and then three-point bending test was performed. In addition, the metal fracture strength was measured by continuing the application of the load. The values were statistically analyzed by performing independent t-tests (α=.05). RESULTS: The mean bond strength of the SLS group (50.60 MPa) was higher than that of the CAST group (46.29 MPa), but there was no statistically significant difference. The metal fracture strength of the SLS group (1087.2 MPa) was lower than that of the CAST group (2399.1 MPa), and this difference was statistically significant. CONCLUSION: In conclusion the balling phenomenon and the gap formation of the SLS process may increase the metal-ceramic bond strength.

Evaluation of process efficiency and bioequivalence of biosimilar recombinant human chorionic gonadotropin (rhCG).

BACKGROUND: Human chorionic gonadotropin (hCG) is a therapeutic protein used for ovulation induction in women with infertility. Dong-A Pharm. Co. has developed recombinant hCG (rhCG) [product code DA-3803] produced in Chinese hamster ovary cells and evaluated its biologic properties, such as biologic potency, efficacy, and pharmacokinetic profile, compared with a reference product, Ovidrel®. OBJECTIVE: The purpose of this study was to evaluate the efficiency of the purification process of Dong-A rhCG (DA-3803) and its bioequivalence from a biosimilar perspective. METHODS: The efficiency of the purification process was estimated through scale-down clearance studies for viruses, endotoxins, host cell DNAs (HCDs) and host cell proteins (HCPs). To confirm bioequivalence, the in vivo/in vitro biologic potency, ovulation induction rate, and pharmacokinetic profile of DA-3803 were compared with those of Ovidrel®. RESULTS: In the clearance studies, the lowest log reduction value (LRV) for model viruses was 8.43. LRVs for endotoxins, HCDs, and HCPs were greater than 5.27, 16.36, and 3.37, respectively. DA-3803 showed equivalent potency with Ovidrel®, and similarity between DA-3803 and Ovidrel® was observed in an efficacy evaluation that measured ovulation induction. The bioequivalence was also confirmed in a rat pharmacokinetic study, which compared pharmacokinetic parameters such as maximum serum concentration, area under the concentration-time curve, time to reach maximum serum concentration, and half-life. In a comparison of different isoform groups of DA-3803, it was shown that the potency and pharmacokinetic profile depend on the sialic acid content. CONCLUSION: The purification process of DA-3803 was effective in removing the major process impurities, and DA-3803 showed similar biologic properties to the reference drug, Ovidrel®.