Poly(ß-amino ester) polymer library with monomer variation for mRNA delivery.

Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines. We created a library of poly(ß-amino ester) (PBAE) polymers by combining various amine monomers and acrylate monomers. Through screening this polymer library, we identified specific polymer nanoparticles (PNPs) that demonstrated high mRNA expression efficiency, with sustained mRNA expression for up to two weeks. Furthermore, the PNPs showed mRNA expression only at the injection site and did not exhibit liver toxicity. Additionally, when assessing immune activation, the PNPs significantly induced T-cell immune activation and were effective in the plaque reduction neutralization test. These results suggest that polymer-based mRNA delivery systems not only hold potential for use in mRNA vaccines but also show promise for therapeutic applications.

Innate immune responses against mRNA vaccine promote cellular immunity through IFN-ß at the injection site.

mRNA vaccines against SARS-CoV-2 have revolutionized vaccine development, but their immunological mechanisms are not fully understood. Here, we investigate injection site responses of mRNA vaccines by generating a comprehensive single-cell transcriptome profile upon lipid nanoparticle (LNP) or LNP-mRNA challenge in female BALB/c mice. We show that LNP-induced stromal pro-inflammatory responses and mRNA-elicited type I interferon responses dominate the initial injection site responses. By tracking the fate of delivered mRNA, we discover that injection site fibroblasts are highly enriched with the delivered mRNA and that they express IFN-ß specifically in response to the mRNA component, not to the LNP component of mRNA vaccines. Moreover, the mRNA-LNP, but not LNP alone, induces migratory dendritic cells highly expressing IFN-stimulated genes (mDC_ISGs) at the injection site and draining lymph nodes. When co-injected with LNP-subunit vaccine, IFN-ß induces mDC_ISGs at the injection site, and importantly, it substantially enhances antigen-specific cellular immune responses. Furthermore, blocking IFN-ß signaling at the injection site significantly decreases mRNA vaccine-induced cellular immune responses. Collectively, these data highlight the importance of injection site fibroblasts and IFN-ß signaling during early immune responses against the mRNA vaccine and provide detailed information on the initial chain of immune reactions elicited by mRNA vaccine injection.

Immunogenicity and Cross-Protection Efficacy of a Genotype F-Derived Attenuated Virus Vaccine Candidate against Mumps Virus in Mice.

Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain Jeryl Lynn (JL) is declining as genotype A is no longer predominant; therefore, a new vaccine strain and booster vaccine are required. We generated a cell culture-adapted MuV genotype F called F30 and evaluated its immunogenicity and cross-protective activity against diverse genotypes. F30 genome nucleotide sequence determination revealed changes in the NP, L, SH, and HN genes, leading to five amino acid changes compared to a minimally passaged stock (F10). F30 showed delayed growth, smaller plaque size in Vero cells, and lower neurotoxicity in neonatal mice than F10. Furthermore, F30 was immunogenic to other genotypes, including the JL vaccine strain, with higher efficacy than that of JL for homologous and heterologous immunization. Further, F30 exhibited cross-protective immunity against MuV genotypes F and G in Ifnar-/- mice after a third immunization with F30 following two doses of JL. Our data suggest that the live-attenuated virus F30 could be an effective booster vaccine to control breakthrough infections and mumps epidemics.

Booster doses of an inactivated F genotype mumps vaccine enhance immunogenicity in mice.

The mumps virus (MuV) causes a highly contagious human disease characterized by swelling of the parotid glands. Although the administration of an attenuated Jeryl Lynn (JL) MuV vaccine shows efficacy in reducing the incidence of MuV infection, sporadic mumps outbreaks still occur in vaccinated populations. We have previously established that an inactivated F genotype mumps vaccine has a higher neutralizing antibody titer against diverse circulating mumps viruses in mice. Here, we aimed to develop a vaccination strategy to enhance the immune response for MuV and assess the effects of heterologous vaccination compared with homologous approaches. We administered an inactivated F genotype mumps vaccine booster following a homologous prime-boost regime and compared its efficacy with three doses of homologous JL vaccine in mice. We demonstrated robust stimulation of neutralizing antibodies and cellular immune response of interferon-γ-secreting cytotoxic T cells following administration of an inactivated F genotype mumps vaccine booster after a homologous prime-boost regime with JL. Compared with the homologous prime-boost regime, this heterologous prime-boost regime showed protective efficacy against the F genotype of MuV. These findings suggest that the heterologous vaccination strategy based on the administration of an inactivated F genotype mumps vaccine provides more effective cross-protection against circulating wild-type mumps viruses than homologous vaccination.

Live attenuated smallpox vaccine candidate (KVAC103) efficiently induces protective immune responses in mice.

Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it was declared to be eradicated and the national immunization program against it was stopped, the variola virus has become a prospective bio-weapon. It is necessary to develop a safe vaccine that protects people from terrorism using this biological weapon and that can be administered to immunocompromised people. Our previous study reported on the development of an attenuated smallpox vaccine (KVAC103). This study evaluated cellular and humoral immune responses to various doses, frequencies, and routes of administration of the KVAC103 strain, compared to CJ-50300 vaccine, and its protective ability against the wild-type vaccinia virus Western Reserve (VACV-WR) strain was evaluated. The binding and neutralizing-antibody titers increased in a concentration-dependent manner in the second inoculation, which increased the neutralizing-antibody titer compared to those after the single injection. In contrast, the T-cell immune response (interferon-gamma positive cells) increased after the second inoculation compared to that of CJ-50300 after the first inoculation. Neutralizing-antibody titers and antigen-specific IgG levels were comparable in all groups administered KVAC103 intramuscularly, subcutaneously, and intradermally. In a protective immunity test using the VACV-WR strain, all mice vaccinated with CJ-50300 or KVAC103 showed 100% survival. KVAC103 could be a potent smallpox vaccine that efficiently induces humoral and cellular immune responses to protect mice against the VACV-WR strain.

Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.

Recombinant measles virus encoding the spike protein of SARS-CoV-2 efficiently induces Th1 responses and neutralizing antibodies that block SARS-CoV-2 variants.

Owing to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the development of effective and safe vaccines has become a priority. The measles virus (MeV) vaccine is an attractive vaccine platform as it has been administered to children for more than 40 years in over 100 countries. In this study, we developed a recombinant MeV expressing the full-length SARS-CoV-2 spike protein (rMeV-S) and tested its efficacy using mouse and hamster models. In hCD46Tg mice, two-dose rMeV-S vaccination induced higher Th1 secretion and humoral responses than one-dose vaccination. Interestingly, neutralizing antibodies induced by one-dose and two-dose rMeV-S immunization effectively blocked the entry of the α, ß, γ, and δ variants of SARS-CoV-2. Furthermore, two-dose rMeV-S immunization provided complete protection against SARS-CoV-2 in the hamster model. These results suggest the potential of rMeV-S as a vaccine candidate for targeting SARS-CoV-2 and its variants.

Immunogenicity of candidate SARS-CoV-2 DNA vaccines based on the spike protein.

Coronavirus disease 2019 caused by the novel human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a major threat to public health worldwide. To deal with the needs of vaccine, we developed four DNA vaccine candidates against SARS-CoV-2, based on the full-length spike (S) or truncated S protein. Following mice vaccination, we measured T-cell response and antigen-specific neutralizing antibody (NAb) titer. All four candidates induced humoral immune responses, including elevated levels of total IgG and NAbs, and cell-mediated immune responses, including multiple cytokine expression. However, the full-length S DNA vaccine enhanced the immune responses most significantly. We then evaluated its appropriate antigen dose and vaccination schedule. Although all immunized groups showed higher immune response than the control group, inoculation with 50 µg antigen led to the highest NAb titer. Immunity was significantly increased after the third inoculation. Thus, the full-length S DNA vaccine can potentially prevent SARS-CoV-2 infection.

Comparison of plaque reduction and focus reduction neutralization tests for the measurement of neutralizing antibody titers against japanese encephalitis virus.

Japanese encephalitis is prevalent throughout the temperate and tropical regions of Asia and is caused by the Japanese encephalitis virus (JEV), a mosquito-borne viral pathogen. The plaque reduction neutralization test (PRNT) is currently recommended as the gold standard test for detecting human antibodies against JEV. The plaque assay is the most widely used method for detecting infectious virions and involves counting discrete plaques in cells. However, it is time-consuming, and results can be subjective (owing to analyst variability during manual plaque counting). The focus reduction neutralization test (FRNT), which is based on an immuno-colorimetric assay, can be used to automatically count foci formed by the JEV. Here, we compared the efficacy of PRNT and FRNT in measuring the neutralizing antibody titers using 102 serum samples from vaccinated and unvaccinated individuals. We observed positive correlations between these neutralization assays against the Nakayama and Beijing strains (R2 = 0.98 and 0.77, respectively). Thus, FRNT may be preferable to PRNT for evaluating the efficacy of JEV vaccines in large-scale serological studies.

Low-Temperature Multiple Micro-Dispensing on Microneedles for Accurate Transcutaneous Smallpox Vaccination.

Smallpox is an acute contagious disease caused by the variola virus. According to WHO guidelines, the smallpox vaccine is administrated by scarification into the epidermis using a bifurcated needle moistened with a vaccine solution. However, this invasive vaccination method involving multiple skin punctures requires a special technique to inoculate, as well as a cold chain for storage and distribution of vaccine solutions containing a live virus. Here, we report a transcutaneous smallpox vaccination using a live vaccinia-coated microneedle (MN) patch prepared by a low-temperature multiple nanoliter-level dispensing system, enabling accurate transdermal delivery of live vaccines and maintenance of bioactivity. The live vaccinia in hyaluronic acid (HA) solutions was selectively coated on the solid MN tips, and the coating amount of the vaccine was precisely controlled through a programmed multiple dispensing process with high accuracy under low temperature conditions (2-8 °C) for smallpox vaccination. Inoculation of mice (BALB/C mouse) with the MN patch coated with the second-generation smallpox vaccine increased the neutralizing antibody titer and T cell immune response. Interestingly, the live vaccine-coated MN patch maintained viral titers at -20 °C for 4 weeks and elevated temperature (37 °C) for 1 week, highlighting improved storage stability of the live virus formulated into coated MN patches. This coated MN platform using contact dispensing technique provides a simple and effective method for smallpox vaccination.

Negligible Effect of Quercetin in the Pharmacokinetics of Sulfasalazine in Rats and Beagles: Metabolic Inactivation of the Interaction Potential of Quercetin with BCRP.

Breast cancer resistance protein (BCRP) mediates pharmacokinetic drug interactions. This study evaluated the potential of quercetin to inhibit and induce BCRP in vitro and in vivo. The inhibition of BCRP was investigated for quercetin and its metabolites using BCRP/mBcrp1-overexpressing MDCKII cells by flow cytometry. The induction of BCRP was investigated in LS174T cells using quantitative PCR. The expression of rat BCRP in rat small intestine, liver, and kidney was also measured after multiple administrations of quercetin in rats (50, 100, and 250 mg/kg, seven days). The in vivo pharmacokinetic changes of sulfasalazine following single or multiple administration of quercetin in rats and beagles were investigated. Although the induction effect of quercetin on BCRP was observed in vitro, the in vivo expression of rat BCRP was not changed by multiple quercetin administrations. Oral administration of quercetin did not affect the plasma concentration or pharmacokinetic parameters of sulfasalazine, regardless of dose and dosing period in either rats or beagles. In addition, the inhibitory effect of quercetin metabolites on BCRP/mBcrp1 was not observed. These results suggest that the in vivo drug interaction caused by quercetin via BCRP was negligible, and it may be related to the metabolic inactivation of quercetin for the inhibition of BCRP.

Robust Construction Safety System (RCSS) for Collision Accidents Prevention on Construction Sites.

A proximity warning system to detect the presence of a worker/workers and to warn heavy equipment operators is highly needed to prevent collision accidents at construction sites. In this paper, we developed a robust construction safety system (RCSS), which can activate warning devices and automatically halt heavy equipment, simultaneously, to prevent possible collision accidents. The proximity detection of this proposed system mainly relies on ultra-wideband (UWB) sensing technologies, which enable instantaneous and simultaneous alarms on (a) a worker's personal safety (personal protection unit (PPU)) device and (b) hazard area device (zone alert unit (ZAU)). This system also communicates with electronic control sensors (ECSs) installed on the heavy equipment to stop its maneuvering. Moreover, the RCSS has been interfaced with a global positioning system communication unit (GCU) to acquire real-time information of construction site resources and warning events. This enables effective management of construction site resources using an online user interface. The performance and effectiveness of the RCSS have been validated at laboratory scale as well as at real field (construction site and steel factory). Conclusively, the RCSS can significantly enhance construction site safety by pro-actively preventing collision of a worker/workers with heavy equipment.

Differences in heritability of craniofacial skeletal and dental characteristics between hypo- and hyper-divergent patterns using Falconer's method and principal component analysis.

OBJECTIVES: To investigate the difference in heritability of craniofacial skeletal and dental characteristics between hypodivergent and hyperdivergent patterns. MATERIALS AND METHODS: 53 Korean adult monozygotic (MZ) and dizygotic (DZ) twins and their siblings were divided into a hypodivergent group (Group 1, SN-MP < 35°, 17 MZ pairs; 11 DZ and sibling [DS] pairs of the same gender) and hyper-divergent group (Group 2, SN-MP > 35°, 16 MZ pairs; 9 DS pairs of the same gender). A total of 56 cephalometric variables were measured using lateral cephalographs. Craniofacial structures were divided into anteroposterior, vertical, dental, mandible, and cranial base characteristics. Falconer's method was used to calculate heritability (h2 > 0.8, high). After principal component analysis (PCA), the mean h 2 value of each component was calculated. RESULTS: Group 1 exhibited high heritability values in shape and position of the mandible, vertical angular/ratio variables, cranial base shape, and maxillary incisor inclination. Group 2 showed high heritability values in anteroposterior position of the maxilla, intermaxillary relationship, vertical angular variables, cranial base length, and mandibular incisor inclination. Occlusal plane inclination showed high heritability in both groups. Although vertical structure presented a high overall mean h 2 value in Group 1, there were no structures that exhibited a high overall mean h 2 value in Group 2. PCA derived 10 components with 91.2% and 92.7% of cumulative explanation in Groups 1 and 2, respectively. CONCLUSIONS: It is necessary to estimate or predict growth according to vertical pattern for providing differential diagnosis and orthodontic/orthopedic treatment planning.

A Prospective Study with Cage-Only or Cage-with-Plate Fixation in Anterior Cervical Discectomy and Interbody Fusion of One and Two Levels.

OBJECTIVE: The authors prospectively analyzed the effect of one-level or two-level anterior cervical discectomy and fusion (ACDF), comparing stand-alone cages and cage-with-plate fixation constructs with respect to clinical outcomes and radiologic changes. METHODS: A total of 84 patients who underwent one-level (n=52) or two-level ACDF (n=32) for cervical disc disease and who completed 2 years of follow-up were included in this study. The patients were divided by cervical level and grouped into ACDF-Cage-only and ACDF-Cage-with-plate groups. The following parameters were assessed using radiographs: subsidence, C2-C7 lordosis angle, fusion segment angle, adjacent disc space narrowing, and fusion status. Clinical outcomes were assessed using the neck disability index (NDI) and visual analog scale scores for arm pain. RESULTS: In the comparison of one-level ACDF-cage-only and ACDF-cage-with-plate groups, the NDI score was better in the cage-only group at the 3-, 12-, and 24-month follow-ups: however, no significant difference in clinical outcomes was observed. In the comparison of two-level ACDF-cage-only and ACDF-cage-with-plate groups, no difference in any clinical outcome was observed between the two groups. At the 24-month follow-up, subsidence was observed in 45.8% of patients in the one-level cage-only group and 32.1% of patients in the one-level cage-with-plate fixation group. There was no statistically significant difference in the incidence rate between the two groups (p=0.312). Subsidence in the two-level cage-only group (66.6%) was significantly more frequent than in the two-level cage-with-plate fixation group (30%; p=0.049). The fusion rate for patients in the one-level cage-only group was not significantly different from that in the one-level cage-with-plate fixation group (cage-only, 87.5%; cage-with-plate fixation, 92.9%; p=0.425); fusion rate in the two-level patients were also similar between groups (cage-only, 83.3%; cage-with-plate fixation, 95%; p=0.31). CONCLUSION: Our clinical results showed that for single-level cases, plate fixation had no additional benefit versus cage-only; for two-level ACDF cases, the fusion rate and clinical outcomes were similar, although the cage-with-plate fixation group had a lower incidence of cage subsidence than did the cage-only group. We conclude that physicians should be aware of this possible disadvantage associated with using cervical plates in one-level ACDF. However, in two-level ACDF, subsidence is more likely to occur without plate fixation, and thus the addition of plate fixation should be considered.

Three-dimensional virtual-surgery simulation-assisted asymmetric bilateral mandibular distraction osteogenesis for a patient with bilateral condylar fractures.

INTRODUCTION: Our objective was to report a patient treated with 3-dimensional virtual-surgery simulation-assisted asymmetric bilateral mandibular distraction osteogenesis. METHODS: A boy (age, 9.5 years) had mandibular hypoplasia and facial asymmetry, induced by bilateral condylar fractures at 4 years of age. The asymmetric bilateral mandibular distraction osteogenesis was planned to correct facial asymmetry and mandibular hypoplasia. The 3-dimensional virtual-surgery simulation results were 11 mm of horizontal distraction on the right side and 4.5 mm of horizontal and 18 mm of vertical distraction on the left side of the mandible. Bilateral ramus osteotomies were performed, and intraoral unidirectional distraction devices were inserted. After a 6-day latency period, distraction was performed at 1 mm per day, followed by a 5-month consolidation period. Transarch and interarch elastics and an acrylic plate were used during distraction and consolidation. Total treatment time was 30 months. RESULTS: Satisfactory outcomes were obtained (achievement ratios between postconsolidation results and simulated results: gonial angle, 106% and 103.9%; mandibular body length, 94.2% and 89.9%; ramus height, 104.1% and 94.5% [values of the right and left sides, respectively]). The chin-point deviation and the transverse cant of the maxillary occlusal plane were significantly improved (10.1 mm to 3.3 mm; -6.8° to -4.4°). At 53 months of follow-up, the Class I molar relationship was well maintained. The transverse cant of the maxillary occlusal plane was slightly improved to -3.7° during pubertal growth. CONCLUSIONS: Three-dimensional virtual-surgery simulation can help clinicians to determine the optimal vector and amount of distraction with high accuracy in complex cases requiring simultaneous correction of a hypoplastic mandible and facial asymmetry.

A collaborative study of an alternative in vitro potency assay for the Japanese encephalitis vaccine.

The use of inactivated Japanese encephalitis (JE) vaccines has been ongoing in East Asia for 40 years. A mouse immunogenicity assay followed by a Plaque Reduction Neutralization (PRN) Test (PRNTest) is currently recommended for each lot release of the vaccine by many national authorities. We developed an alternative in vitro ELISA to determine the E antigen content of the Japanese encephalitis virus to observe the 3Rs strategy. A collaborative study for replacing the in vivo potency assay for the Japanese encephalitis vaccine with the in vitro ELISA assay was confirmed comparability between these two methods. The study demonstrated that an in vitro assay could perform faster and was more convenient than the established in vivo PRNTest. Moreover, this assay had better precision and reproducibility compared with the conventional in vivo assay. Additionally, the content of antigen determined using the in vitro ELISA correlated well with the potency of the in vivo assay. Furthermore, this method allowed discrimination between individual lots. Thus, we propose a progressive switch from the in vivo assay to the in vitro ELISA for JE vaccine quality control.

Clinical and Radiological Comparison of Semirigid (WavefleX) and Rigid System for the Lumbar Spine.

OBJECTIVE: Spinal fusion operation is an effective treatment in the spinal pathology, but it could change the physiological distribution of load at the instrumented and adjacent segments. This retrospective study compared the radiological and clinical outcomes of patients undergoing lumbar fusion with semirigid rods versus rigid rods system. METHODS: Using transpedicular fixation and posterior lumbar interbody fusion at the level of L4/L5, 20 patients were treated with semirigid rods (WavefleX, SR group), and 20 patients with rigid rods (titanium, RR group). Clinical and radiological outcomes were evaluated, including visual analog score for lower back pain and leg pain, Prolo functional and economic scores, statues of implanted instruments, fusion rate, and complications during 24-month follow-up. RESULTS: Clinical scores were significantly improved until postoperative 24-month follow-up as compared with preoperative scores in both groups (p<0.05), with similar levels of improvement observed at the same time points postoperatively between the 2 groups. Prolo economic scores were significantly improved in SR group compared to RR until 12 months, but this improvement became similar after 18 months. The overall fusion rate was 94.1% until the 24-month follow-up for both groups. No significant complication was observed in both groups. CONCLUSION: The results of the present study indicate that semirigid rods system with posterior lumbar interbody fusion showed similar clinical and radiological result with rigid rods system until 2 years after instrumentation. The WavefleX rods system, as a semirigid rods with unique characteristics, may be an effective alternative treatment for patients in lumbar fusion.

Standardization of the methods and reference materials used to assess virus content in varicella vaccines.

BACKGROUND: In Korea, every vaccine lot is tested by the National Center for Lot Release (NCLR) in accordance with the national lot release procedures to ensure the safety and efficacy of vaccines. These quality tests examine the virus content in varicella vaccines via plaque assays (either the agar overlay method [AOM] or plaque staining method [PSM]), according to the procedures suggested by the Korean Reference Material for the Varicella Vaccine (KRMVV) or the manufacturer's standard in-house protocol. AIM: To standardize the virus content tests, viral titers in the KRMVV were measured using the PSM at four participating laboratories in a collaborative study. With the aim of developing a standardized method using the KRMVV as a positive control, we compared the ability of the two test methods, AOM and PSM, to accurately and reproducibly determine the virus content of two commercial varicella vaccines. RESULTS: The results showed that the standardized method (PSM) was more suitable for quality control analysis of the varicella vaccine. CONCLUSION: Use of a standardized method (PSM) according to the Korean reference material will improve the reliability and objectivity of lot release testing.

Change in maxillary incisor inclination during surgical-orthodontic treatment of skeletal Class III malocclusion: comparison of extraction and nonextraction of the maxillary first premolars.

INTRODUCTION: The purpose of this study was to investigate differences in preoperative decompensation and postoperative compensation of the maxillary incisors in patients with skeletal Class III malocclusion treated with 2-jaw surgery and extraction or nonextraction of the maxillary first premolars. METHODS: The subjects consisted of 50 skeletal Class III patients who had a normal maxillary position, prognathic mandible, and mild crowding in the maxillary arch (≤4 mm). All patients were treated with 2-jaw surgery. They were divided into 2 groups: group 1 (n = 25) had extraction of the maxillary first premolars, and group 2 (n = 25) had no extractions. Lateral cephalograms were analyzed before treatment (T0), 1 month before surgery (T1), 1 day after surgery (T2), and after debonding (T3). After measurement of the skeletodental variables, statistical analyses were performed. RESULTS: At T0, group 1 exhibited more compensated maxillary incisors compared with group 2 (U1-SN, P <0.001). Considerable preoperative decompensation in group 1 and negligible preoperative decompensation in group 2 occurred at T1 (ΔU1-SN, -9.1° vs 1.1°). Although maxillary incisor inclination significantly decreased with surgical movement of the maxilla at T2, this increased to compensate for the postsurgical skeletal relapse in both groups at T3. Although 24% of group 1 had a normal range of maxillary incisor inclination (U1-SN) at T0, it increased to 68% at T1. A dominant pattern of the subjects within the normal range of U1-SN was maintained in groups 1 and 2 (80% and 96% at T2, and 72% and 80% at T3, respectively). According to the achievement ratio, the U1-SN value became close to the norm mainly by preoperative decompensation in group 1 (95.5%) and by surgery in group 2 (130.2%). CONCLUSIONS: The results of this study might provide effective guidelines for predicting the amount and pattern of preoperative decompensation and postoperative compensation of the maxillary incisors in skeletal Class III patients treated with 2-jaw surgery.