Correlation between Collagen Type I/III Ratio and Scar Formation in Patients Undergoing Immediate Reconstruction with the Round Block Technique after Breast-Conserving Surgery.

The aim of this study was to investigate the relationship between the collagen type I/III ratio and scarring in patients who underwent immediate reconstruction with the round block technique (RBT) after breast conservation surgery. Seventy-eight patients were included, and demographic and clinical characteristics were recorded. The collagen type I/III ratio was measured using immunofluorescence staining and digital imaging, and scarring was assessed using the Vancouver Scar Scale (VSS). The mean VSS scores were 1.92 ± 2.01 and 1.79 ± 1.89, as assessed by two independent plastic surgeons, with good reliability of the scores. A significant positive correlation was found between VSS and the collagen type I/III ratio (r = 0.552, p < 0.01), and a significant negative correlation was found between VSS and the collagen type III content (r = -0.326, p < 0.05). Multiple linear regression analysis showed that the collagen type I/III ratio had a significant positive effect on VSS (ß = 0.415, p = 0.028), whereas the collagen type I and collagen type III content had no significant effect on VSS. These findings suggest that the collagen type I/III ratio is associated with scar development in patients undergoing RBT after breast conservation surgery. Further research is needed to develop a patient-specific scar prediction model based on genetic factors affecting the collagen type I/III ratio.

Is the retroauricular region a suitable donor site for full-thickness skin grafting in the era of mask wearing?

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the everyday use of face masks massively increased to prevent the spread of infection. Many people complain of ear pain and erosion when wearing a mask for extended periods of time. If prolonged mask usage is uncomfortable for ordinary people, a question arises-how much more inconvenient must mask wearing be for patients with a full-thickness skin graft (FTSG) donor site in the retroauricular region? Herein, we evaluated complications related to face mask use in 27 patients with a retroauricular FTSG donor site, with the goal of clarifying whether the retroauricular region is still an appropriate FTSG donor site in the context of the COVID-19 pandemic. METHODS: Complications in 27 patients treated by FTSGs harvested from the retroauricular region from 2019 to 2021 were investigated. A questionnaire comparing the normal and the operated sides was administered. Pain, itching, soreness, deformity, and symmetry were further investigated. RESULTS: Pain and itching were the only observed complications. The operated side was slightly more painful than the normal side in four patients (14.8%), and four patients (14.8%) reported itching on the operated side. However, all patients who experienced complications stated that the pain or itching did not interfere with mask wearing. Most symptomatic patients were older than 60 years of age (23.8%, p=0.185) and wore masks for longer periods of time (28.5%, p=0.326). CONCLUSION: Few retroauricular donor site-related complications occurred, and none of these complications caused inconvenience in daily life. Therefore, in the COVID-19 pandemic, the use of the retroauricular region as an FTSG donor site remains appropriate.

An Alternative Splicing Variant of the Mixed-Lineage Leukemia 5 Protein Is a Cellular Adhesion Receptor for ScaA of Orientia tsutsugamushi.

Scrub typhus is a mite-borne disease caused by the obligately intracellular bacterium Orientia tsutsugamushi. We previously demonstrated that ScaA, an autotransporter membrane protein of O. tsutsugamushi, is commonly shared in various genotypes and involved in adherence to host cells. Here, we identified a mixed-lineage leukemia 5 (MLL5) mammalian trithorax group protein as a host receptor that interacts with ScaA. MLL5, identified by yeast two-hybrid screening, is an alternative splicing variant of MLL5 (vMLL5) which contains 13 exons with additional intron sequences encoding a tentative transmembrane domain. Indeed, vMLL5 is expressed on the plasma membrane as well as in intracellular compartments in eukaryotic cells and colocalized with adherent O. tsutsugamushi. In addition, ScaA-expressing Escherichia coli showed significantly increased adherence to vMLL5-overexpressing cells compared with vector control cells. We mapped the C-terminal region of the passenger domain of ScaA as a ligand for vMLL5 and determined that the Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain of MLL5 is an essential and sufficient motif for ScaA binding. We observed significant and specific inhibition of bacterial adhesion to host cells in competitive inhibition assays using the C-terminal fragment of ScaA or the SET domain of vMLL5. Moreover, immunization with the C-terminal fragment of ScaA provided neutralizing activity and protective immunity against lethal challenge with O. tsutsugamushi as efficiently as vaccination with the whole passenger domain of ScaA. These results indicate that vMLL5 is a novel cellular receptor for ScaA-mediated adhesion of O. tsutsugamushi and facilitates bacterial adhesion to host cells, thereby enhancing bacterial infection. IMPORTANCE O. tsutsugamushi is a mite-borne pathogen that causes scrub typhus. As an obligately intracellular pathogen, its adhesion to and invasion of host cells are critical steps for bacterial growth. However, the molecular basis of the bacterial ligand and host receptor interaction is poorly defined. Here, we identified a splicing variant of MLL5 (vMLL5) as a cellular adhesion receptor of ScaA, an outer membrane autotransporter protein of O. tsutsugamushi. We mapped the interacting domains in the bacterial ligand and host receptor and confirmed their functional interaction. In addition, immunization with the C-terminal region of ScaA, which involves an interaction with the SET domain of vMLL5, not only induces enhanced neutralizing antibodies but also provides protective immunity against lethal challenge with O. tsutsugamushi.

Correlation between acellular dermal matrix (ADM) volume and breast implant size selection among patients undergoing prepectoral direct-to-implant (DTI) breast reconstruction using complete ADM.

BACKGROUND: In prepectoral direct-to-implant breast reconstruction using the acellular dermal matrix (ADM)-assisted technique, breast volume asymmetry can occur. We hypothesized that ADM size influences implant size selection in prepectoral breast reconstruction with implant coverage using an ADM. We investigated factors influencing implant size selection and provide guidelines for surgeons. METHODS: A retrospective chart review was performed to identify all patients who underwent prepectoral direct-to-implant breast reconstruction between January 2017 and October 2020. We assessed patient characteristics, preoperative expected implant volume, ADM size, volume of implant used in surgery, and symmetry scale of aesthetic item scale (AIS) 6 months after surgery. We compared the symmetry score of AIS between a group in which the preoperative expected silicone implant size (ES) was used and a group in which a silicone implant of a smaller size than planned (SS) was used. RESULTS: Patient characteristics, including age, body mass index (BMI), and excised breast volume, were similar between the groups (P > .05). ADM size had a significant effect on implant size selection (odds ratio = 1.760, P < .01). The symmetry score of AIS was higher in the SS group. CONCLUSIONS: ADM size must be considered when selecting implant size in prepectoral direct-to-implant breast reconstruction using the ADM-assisted technique.

Changing Susceptibility of Staphylococci in Patients with Implant-Based Breast Reconstructions: A Single-Center Experience.

Background and Objectives: Infections and capsular contractures remain unresolved issues in implant-based breast reconstruction. Capsular contractures are thought to be caused by the endogenous flora of the nipple duct. However, little is known about the antibiotic susceptibility of the microorganisms involved. This study aimed to evaluate the composition of endogenous breast flora and its antimicrobial susceptibility in patients with breast cancer. This study will aid in selecting a prophylactic antibiotic regimen for breast reconstruction surgery. Materials and Methods: We obtained bacteriologic swabs from the nipple intraoperatively in patients who underwent implant-based breast reconstruction following nipple-sparing mastectomy between January 2019 and August 2021. Antibiotic susceptibility tests were performed according to the isolated bacteriology. Statistical analysis was performed based on several patient variables to identify which factors influence the antibiotic resistance rate of endogenous flora. Results: A total of 125 of 220 patients had positive results, of which 106 had positive culture results for coagulase-negative Staphylococcus species (CoNS). Among these 106 patients, 50 (47%) were found to have methicillin-resistant staphylococci, and 56 (53%) were found to have methicillin-susceptible staphylococci. The methicillin resistance rate in the neoadjuvant chemotherapy group (56.3%) was significantly higher (OR, 2.3; p = 0.039) than that in the non-neoadjuvant chemotherapy group (35.5%). Conclusions: Based on the results, demonstrating high and rising incidence of methicillin-resistant staphylococci of nipple endogenous flora in patients with breast cancer compared to the past, it is necessary to consider the selection of prophylactic antibiotics to reduce infections and capsular contracture after implant-based breast reconstruction.

"Tear-Drop Appearance" Wrap: A Novel Implant Coverage Method for Creating Natural Contour in Prepectoral Prosthetic-Based Breast Reconstruction.

Various implant wrapping methods with acellular dermal matrix (ADM) have been introduced, but most focus on random trimming and suturing aimed to maximize implant coverage. Here we present our clinical experience using a "tear-drop appearance" wrapping method to achieve natural contours through upper pole volume replacement. We retrospectively reviewed the data of 56 consecutive cases of prepectoral prosthetic-based breast reconstruction (PPBR) using this wrapping method following nipple-sparing mastectomy between March 2020 and June 2021. The "tear-drop appearance" wrapping design creates an anatomical tear-drop-shaped pocket to encourage lower pole fullness and create a natural contour through upper pole volume replacement by ADM. Patients' baseline characteristics, operative data, and complications were analyzed. Aesthetic outcomes were measured using the BREAST-Q and Aesthetic Item Scale (AIS). A successful reconstruction was achieved without major complications and using a single ADM sheet. Four types and three sizes of ADMs were used. The mean resected breast tissue weight was 274.3 g, while the mean implant volume was 230.0 cc. The average BREAST-Q and AIS scores were 4.6 ± 0.8 and 4.5 ± 0.7, respectively. Owing to its simplicity, reproducibility, and effectivity, this method is an excellent implant coverage option that achieves a natural contour in PPBR.

Review of 107 Oncoplastic Surgeries Using an Acellular Dermal Matrix with the Round Block Technique.

The round block technique (RBT) is an oncoplastic surgery method that uses volume displacement techniques after partial mastectomy. However, cosmetic problems occur after tissue rearrangement in patients with small breasts or those in whom a large amount of breast tissue is excised. Therefore, we used an acellular dermal matrix (ADM) when the volume was insufficient after tissue rearrangement. Patients who underwent breast reconstruction using the ADM with the RBT after breast-conserving surgery (BCS) were included. The ADM graft was performed in two layers. First, it was placed on the glandular flap, and the patient was then seated to ascertain the degree of deformity. If the volume was insufficient, a graft was also performed under the skin flap. Overall, 107 oncoplastic surgeries were performed. Tumors were most commonly located in the upper outer quadrant of the breast, and the mean resected breast tissue was 27.1 g. Seroma was the most common complication, but it improved with several aspirations. There were no major complications or cosmetic problems requiring reoperation. Therefore, if the ADM was used for defects that could not be reconstructed with the RBT alone, safe and cosmetically good results could be obtained.

Staged Chest Wall Reconstruction for Radiation-induced Costochondritis.

Costochondritis after breast reconstruction and radiation therapy is rarely reported. Moreover, it is difficult to diagnose using computed tomography and magnetic resonance imaging; as such, wound debridement and reconstruction must be performed in several stages. A 51-year-old woman was diagnosed with invasive cancer of the right breast, and she underwent nipple sparing mastectomy and direct-to-implant breast reconstruction in November 2007. Thirteen years later, in September 2020, she experienced pain and swelling on her right breast. Incisional drainage and implant removal were performed in another clinic; however, the infection was not controlled. An implant-induced infection was suspected, and debridement was performed to a level where fresh tissue appeared in the upper layer of the intercostal muscle. Antibiotics and open dressing were used for 10 days; however, yellowish debris was noted, and third to fifth ribs and costal cartilages turned dark brown. Radiation-induced costochondritis was diagnosed based on clinical findings from the intraoperative field, wound course, and cartilage biopsy. Radical chest wall resection and reconstruction was performed using Teflon (Dupont/Chemours, Wilmington, Del.) and latissimus dorsi musculocutaneous flap. The patient was discharged 2 weeks after surgery without any complications. Costochondritis should be clinically diagnosed while performing the first debridement in staged operation. Radical chest wall resection is essential with chest wall reconstruction using Teflon and a latissimus dorsi musculocutaneous flap.

Factors Influencing Patient Satisfaction with Upper Blepharoplasty in Elderly Patients.

Upper blepharoplasty in elderly patients has characteristics that differ from those of younger patients. Blepharoptosis in elderly patients causes not only aesthetic problems but also functional problems such as entropion, visual disturbance, and sore eyes. We hypothesized that factors influencing patient satisfaction with upper blepharoplasty in elderly patients include aesthetic outcomes, functional outcomes, and personal factors. METHODS: This study included 57 patients aged >65 years who underwent upper blepharoplasty between April 2018 and March 2019. All surgeries were performed through the "Upper Blepharoplasty Service Project" of the public health center in Geoje City. To evaluate the individual characteristics of the patients, a preoperative questionnaire (including sociodemographic characteristics, main symptoms of discomfort in the upper eyelid, and degree of expectation of surgical results) was administered to the patients. After 6 months, a satisfaction survey was conducted accordingly. RESULTS: The main symptoms of discomfort were sagging of the skin of the upper eyelid. The mean score for patient satisfaction was 3.84 ± 0.40, and satisfaction with the results of surgery relative to the cost was 4.53 ± 0.63, which was the highest score. Significant verification of the regression coefficients showed that functional improvement and cognitive degree of postsurgery precautions had a significant effect on patient satisfaction, whereas aesthetic outcomes and expectations of surgical results were not correlated with patient satisfaction. CONCLUSION: The findings indicated that elderly patients tended to be satisfied with functional improvement that resolved their symptoms of discomfort and personal factors such as cost and cognitive degree of precautions after upper blepharoplasty.

Reconstruction of a small defect of the lower vermilion adjacent to white roll using a modified O-Z flap.

Reconstruction of lip defects is important because the lips play an important role in maintaining aesthetic facial balance, facial expressions, and speech. There are various methods of lip reconstruction such as primary repair, skin grafting, and utilization of local and free flaps. It is important to select a proper reconstruction method according to the size and location of lip defect. Failure to select an appropriate method may result in distortion, color mismatch, sensory loss, and aesthetic imbalance. Herein we present a case of successful aesthetic reconstruction of the lower vermilion. We removed a venous malformation, which was limited to the lower vermilion and adjacent to the white roll, and repaired the defect using the modified O-Z flap.

The Orientia tsutsugamushi ScaB Autotransporter Protein Is Required for Adhesion and Invasion of Mammalian Cells.

Autotransporter proteins are widely present in Gram-negative bacteria. They play a pivotal role in processes related to bacterial pathogenesis, including adhesion, invasion, colonization, biofilm formation, and cellular toxicity. Bioinformatics analysis revealed that Orientia tsutsugamushi, the causative agent of scrub typhus, encodes six different autotransporter genes (scaA-scaF). Although four of these genes (scaA, scaC, scaD, and scaE) are present in diverse strains, scaB and scaF have been detected in only a limited number of strains. Previous studies have demonstrated that ScaA and ScaC are involved in the adherence of host cells. However, the putative function of other O. tsutsugamushi Sca proteins has not been studied yet. In this study, we show that scaB is transcribed and expressed on the surface of O. tsutsugamushi Boryong strain. Using a heterologous Escherichia coli expression system, we demonstrated that ScaB-expressing E. coli can successfully mediate adherence to and invasion into non-phagocytic cells, including epithelial and endothelial cells. In addition, pretreatment with a recombinant ScaB polypeptide inhibits the entry of O. tsutsugamushi into cultured mammalian cells. Finally, we also identified the scaB gene in the Kuroki and TA686 strains and observed high levels of sequence variation in the passenger domains. Here, we propose that the ScaB protein of O. tsutsugamushi can mediate both adhesion to and invasion into host cells in the absence of other O. tsutsugamushi genes and may play important roles in bacterial pathogenesis.

Retrospective review of 108 breast reconstructions using the round block technique after breast-conserving surgery: Indications, complications, and outcomes.

BACKGROUND: Several oncoplastic approaches have been implemented in recent years to enhance cosmetic results and to reduce complications. The round block technique is a volume displacement technique for breast reconstruction after breast-conserving surgery (BCS). However, its indications are currently limited according to tumor location, and its cosmetic results and complications have not been clearly established. We hypothesized that the round block technique could produce favorable cosmetic results without major complications regardless of tumor location or nipple-tumor distance, below a certain resected tumor volume and tumor-breast volume ratio. METHODS: All breast reconstructions using the round block technique after BCS were included in this analysis. Patients' data were reviewed retrospectively to investigate complications during follow-up, and clinical photos were used to evaluate cosmetic results. The relationships of tumor location, nipple-tumor distance, tumor volume, and the tumor-breast volume ratio with cosmetic results were investigated. RESULTS: In total, 108 breasts were reconstructed. The mean resected tumor volume was 30.2±15.0 mL. The cosmetic score was 4.5±0.6 out of 5. Tumor location, nipple-tumor distance, tumor volume, tumor-breast volume ratio, radiotherapy, and chemotherapy had no significant effects on cosmetic results or complications. There were no major complications requiring reoperation. CONCLUSIONS: Breast reconstruction using the round block technique after BCS can lead to good cosmetic results without major complications regardless of the tumor location, nipple-tumor distance, radiotherapy, or chemotherapy. Below the maximum tumor volume (79.2 mL) and the maximum tumor-breast volume ratio (14%), favorable results were consistently obtained.

Polarized lung inflammation and Tie2/angiopoietin-mediated endothelial dysfunction during severe Orientia tsutsugamushi infection.

Orientia tsutsugamushi infection can cause acute lung injury and high mortality in humans; however, the underlying mechanisms are unclear. Here, we tested a hypothesis that dysregulated pulmonary inflammation and Tie2-mediated endothelial malfunction contribute to lung damage. Using a murine model of lethal O. tsutsugamushi infection, we demonstrated pathological characteristics of vascular activation and tissue damage: 1) a significant increase of ICAM-1 and angiopoietin-2 (Ang2) proteins in inflamed tissues and lung-derived endothelial cells (EC), 2) a progressive loss of endothelial quiescent and junction proteins (Ang1, VE-cadherin/CD144, occuludin), and 3) a profound impairment of Tie2 receptor at the transcriptional and functional levels. In vitro infection of primary human EC cultures and serum Ang2 proteins in scrub typhus patients support our animal studies, implying endothelial dysfunction in severe scrub typhus. Flow cytometric analyses of lung-recovered cells further revealed that pulmonary macrophages (MΦ) were polarized toward an M1-like phenotype (CD80+CD64+CD11b+Ly6G-) during the onset of disease and prior to host death, which correlated with the significant loss of CD31+CD45- ECs and M2-like (CD206+CD64+CD11b+Ly6G-) cells. In vitro studies indicated extensive bacterial replication in M2-type, but not M1-type, MΦs, implying the protective and pathogenic roles of M1-skewed responses. This is the first detailed investigation of lung cellular immune responses during acute O. tsutsugamushi infection. It uncovers specific biomarkers for vascular dysfunction and M1-skewed inflammatory responses, highlighting future therapeutic research for the control of this neglected tropical disease.

Treatment of post-traumatic chin deformities using bilateral botulinum toxin injections.

Post-traumatic hematoma formation is a common complication of contusion. If the hematoma is large enough to aspirate or drain, it can be treated quickly and appropriately. However, if the hematoma is small or concealed by local swelling, it may be overlooked and left untreated. In most cases, a hematoma will resolve following conservative treatment; however, associated infection or muscle fibrosis can occur. Herein, we present the case of a patient with a chin deformity caused by a post-traumatic hematoma. The deformity was treated using botulinum toxin and triamcinolone acetonide injections as minimally invasive treatments. The course of treatment was good.

Metformin Ameliorates Lipotoxic ß-Cell Dysfunction through a Concentration-Dependent Dual Mechanism of Action.

BACKGROUND: Chronic exposure to elevated levels of free fatty acids contributes to pancreatic ß-cell dysfunction. Although it is well known that metformin induces cellular energy depletion and a concomitant activation of AMP-activated protein kinase (AMPK) through inhibition of the respiratory chain, previous studies have shown inconsistent results with regard to the action of metformin on pancreatic ß-cells. We therefore examined the effects of metformin on pancreatic ß-cells under lipotoxic stress. METHODS: NIT-1 cells and mouse islets were exposed to palmitate and treated with 0.05 and 0.5 mM metformin. Cell viability, glucose-stimulated insulin secretion, cellular adenosine triphosphate, reactive oxygen species (ROS) levels and Rho kinase (ROCK) activities were measured. The phosphorylation of AMPK was evaluated by Western blot analysis and mRNA levels of endoplasmic reticulum (ER) stress markers and NADPH oxidase (NOX) were measured by real-time quantitative polymerase chain reaction analysis. RESULTS: We found that metformin has protective effects on palmitate-induced ß-cell dysfunction. Metformin at a concentration of 0.05 mM inhibits NOX and suppresses the palmitate-induced elevation of ER stress markers and ROS levels in a AMPK-independent manner, whereas 0.5 mM metformin inhibits ROCK activity and activates AMPK. CONCLUSION: This study suggests that the action of metformin on ß-cell lipotoxicity was implemented by different molecular pathways depending on its concentration. Metformin at a usual therapeutic dose is supposed to alleviate lipotoxic ß-cell dysfunction through inhibition of oxidative stress and ER stress.

Rhinogenic Headache: Standardization of Terminologies Used for Headaches Arising From Problems in the Nose and Nasal Cavity.

OBJECTIVE: The use of different expressions between physicians frequently results in confusion in the process of diagnosis and treatment of patients with headaches due to problems in the nose and nasal cavity. The aim of this study was to assess the terminologies that have been used most frequently to standardize these terminologies. METHODS: Terminologies that are most frequently used in general, including rhinogenic migraine, sinus headache, rhinogenic contact point headache, middle turbinate headache syndrome, and rhinogenic headache, were found by searching PubMed, Web of Science, and Google Scholar. These terminologies were objectively assessed on the basis of existing research and definitions and the range of diagnoses by organizations with public credibility. RESULTS: There were many terminologies in use for headache related to nose; however, these were not logical expressions and only partly explained the phenomenon. Among the terms, "rhinogenic headache" was most appropriate in expressing and describing the related symptoms. CONCLUSION: The results indicated that the term "rhinogenic headache" is most appropriate for describing pain in the nose and eyes in patients with deformation within the nose or the nasal cavity due to external injuries or underlying diseases related to nose as observed on computed tomography.

Correlation between dermal thickness and scar formation in female patients after thyroidectomy.

BACKGROUND: Minimizing scarring has long been a challenge in plastic surgery. Factors affecting scar formation are well known, but the effect of some patient-specific factors such as dermal thickness remains unverified. Management of factors predictive of scarring can improve postoperative patient satisfaction and scar treatment. METHODS: For 3 years, we used ultrasonography to measure dermal thickness in female patients who had undergone thyroidectomy for cancer at our hospital. We confirmed the influence of dermal thickness on hypertrophic scar formation and the Patient and Observer Scar Assessment Scale scar score 6 months after surgery. RESULTS: There was a positive correlation between dermal thickness and scar score (p<0.05), and dermal thickness appears to be a cause of hypertrophic scar formation (p<0.05). CONCLUSION: Thick dermis was found to cause poor scar formation and hypertrophic scarring. Prediction of factors that can influence scar formation can be used to educate patients before surgery and can help in scar management and improvement in patient satisfaction.

Modified Anterior Craniofacial Osteotomy Using Partial Nasal Bone Division and Reconstruction in Frontoethmoidal Sinus Meningioma.

Typical transcranial approaches are insufficient for adequate visualization and resection of skull base tumors. Different approaches with multiple modifications have been attempted. Here, we describe a new approach for a lesion that is central and hard to treat by conventional craniotomy and successful reconstruction with calvarial bone graft and titanium mesh plate. A 69-year-old female patient presented with recurrent meningioma. The tumor had invaded the frontal lobe, right supraorbital rim, and ethmoidal bone. We performed a modified anterior craniofacial approach that fully exposed the tumor and invaded bone. In consideration of the patient's age and cosmetic result, the tumor and invaded bone was resected and the defect area was reconstructed with titanium mesh and calvarial bone graft. At 6 months postoperative the patient had no complications and was satisfied with the esthetic result. We report this case to demonstrate the successful approach and reconstruction using this technique.

Safe and Effective Method to Transfer Pedicle Vessels in Free Flap Reconstruction.

Free tissue transfer is a useful method to cover soft tissue defects following trauma or tumor excision. At the time of transfer of the pedicle, its status is not investigated. Therefore, kinking of the pedicle can occur, and pedicle injuries can result from surgical instruments. The authors would like to introduce a simple, safe, and effective method to overcome these problems using a Penrose drain. The present method can help reconstructive microsurgeons with the transfer of pedicle vessels through a tunnel without torsion or injury.

Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen.

BACKGROUND: Zinc oxide nanoparticle (ZNP) has been applied in various biomedical fields. Here, we investigated the usage of ZNP as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP. RESULTS: A novel zinc oxide-binding peptide (ZBP), FPYPGGDA, with high affinity to ZNP (K a  = 2.26 × 106 M-1) was isolated from a random peptide library and fused with a bacterial antigen, ScaA of Orientia tsutsugamushi, the causative agent of scrub typhus. The ZNP/ZBP-ScaA complex was efficiently phagocytosed by a dendritic cell line, DC2.4, in vitro and significantly enhanced anti-ScaA antibody responses in vivo compared to control groups. In addition, immunization with the ZNP/ZBP-ScaA complex promoted the generation of IFN-γ-secreting T cells in an antigen-dependent manner. Finally, we observed that ZNP/ZBP-ScaA immunization provided protective immunity against lethal challenge of O. tsutsugamushi, indicating that ZNP can be used as a potent adjuvant when complexed with ZBP-conjugated antigen. CONCLUSIONS: ZNPs possess good adjuvant potential as a vaccine carrier when combined with an antigen having a high affinity to ZNP. When complexed with ZBP-ScaA antigen, ZNPs could induce strong antibody responses as well as protective immunity against lethal challenges of O. tsutsugamushi. Therefore, application of ZNPs combined with a specific soluble antigen could be a promising strategy as a novel vaccine carrier system.