Tissue Engineering and Regenerative Medicine in the Field of Otorhinolaryngology.

BACKGROUND: Otorhinolaryngology is a medical specialty that focuses on the clinical study and treatments of diseases within head and neck regions, specifically including the ear, nose, and throat (ENT), but excluding eyes and brain. These anatomical structures play significant roles in a person's daily life, including eating, speaking as well as facial appearance and expression, thus greatly impacting one's overall satisfaction and quality of life. Consequently, injuries to these regions can significantly impact a person's well-being, leading to extensive research in the field of tissue engineering and regenerative medicine over many years. METHODS: This chapter provides an overview of the anatomical characteristics of otorhinolaryngologic tissues and explores the tissue engineering and regenerative medicine research in otology (ear), rhinology (nose), facial bone, larynx, and trachea. RESULTS AND CONCLUSION: The integration of tissue engineering and regenerative medicine in otorhinolaryngology holds the promise of broadening the therapeutic choices for a wide range of conditions, ultimately improving quality of a patient's life.

Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents.

Using (S)-decursinol isolated from root of Angelica gigas Nakai (AGN), we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited Janus kinase 1 (JAK1) and signal transducer and activator of transcription activation 3 (STAT3) phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.

Microbiomic association between the saliva and salivary stone in patients with sialolithiasis.

Salivary stones, known as sialoliths, form within the salivary ducts due to abnormal salivary composition and cause painful symptoms, for which surgical removal is the primary treatment. This study explored the role of the salivary microbial communities in the formation of sialoliths. We conducted a comparative analysis of microbial communities present in the saliva and salivary stones, and sequenced the 16S rRNA gene in samples obtained from patients with sialoliths and from healthy individuals. Although the diversity in the saliva was high, the essential features of the microbial environment in sialoliths were low diversity and evenness. The association of microbial abundance between stones and saliva revealed a positive correlation between Peptostreptococcus and Porphyromonas, and a negative correlation for Pseudomonas in saliva. The functional potential differences between saliva and stones Bacterial chemotaxis and the citrate cycle were negatively correlated with most genera found in salivary stone samples. However, the functions required for organic compound degradation did not differ between the saliva samples. Although some microbes were shared between the sialoliths and saliva, their compositions differed significantly. Our study presents a novel comparison between salivary stones and salivary microbiomes, suggesting potential preventive strategies against sialolithiasis.

Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads.

Hypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism. Here, we investigated the feasibility of three-dimensional structural microbeads fabricated with TMSCs and alginate, a natural biodegradable polymer, to treat hypoparathyroidism. Alginate microbeads were fabricated by dropping a 2% (w/v) alginate solution containing TMSCs into a 5% CaCl2 solution and then differentiated into parathyroid-like cells using activin A and sonic hedgehog for 7 days. The protein expression of PTH, a specific marker of the parathyroid gland, was significantly higher in differentiated alginate microbeads with TMSCs (Al-dT) compared with in undifferentiated alginate microbeads with TMSCs. For in vivo experiments, we created the hypoparathyroidism animal model by parathyroidectomy (PTX) and implanted alginate microbeads in the dorsal interscapular region. The PTX rats with Al-dT (PTX+Al-dT) showed the highest survival rate and weight change and a gradual increase in serum intact PTH levels. We also detected a higher expression of PTH in retrieved tissues of PTX+Al-dT using immunofluorescence analysis. This study demonstrates that alginate microbeads are potential a new tool as a surgically scalable therapy for treating hypoparathyroidism.

Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

Care and Management of Voice Change in Thyroid Surgery: Korean Society of Laryngology, Phoniatrics and Logopedics Clinical Practice Guideline.

Voice change is a common complaint after thyroid surgery and has a significant impact on quality of life. The Korean Society of Laryngology, Phoniatrics and Logopedics assembled a task force to establish guideline recommendations on education, care, and management related to thyroid surgery. The guideline recommendations encompass preoperative voice education, management of anticipated voice change during surgery, and comprehensive voice care after thyroid surgery, and include in-depth information and up-to-date knowledge based on validated literature. The committee constructed 14 key questions (KQs) in three categories-preoperative (KQ 1-2), intraoperative (KQ 3-8), and postoperative (KQ 9-14) management-and developed 18 evidence-based recommendations. The Delphi survey reached an agreement on each recommendation. A detailed evidence profile is presented for each recommendation. The level of evidence for each recommendation was classified as high-quality, moderate-quality, or low-quality. The strength of each recommendation was designated as strong or weak considering the level of evidence supporting the recommendation. The guidelines are primarily targeted toward physicians who treat thyroid surgery patients and speech-language pathologists participating in patient care. These guidelines will also help primary care physicians, nurses, healthcare policymakers, and patients improve their understanding of voice changes and voice care after thyroid surgery.

Porcine Tracheal Mucosa-Derived Decellularized Patch to Prevent Septal Perforation in a Rabbit Model.

BACKGROUND: Nasal septal perforation is caused by bilateral septal mucosal injuries resulting from nasal trauma and septal surgeries. Previous studies have reported that biocompatible materials may be effective for repairing nasal septal perforations. However, they were primarily used for treatment; no study has investigated their use for prevention of nasal septal perforation. OBJECTIVE: To determine whether porcine tracheal mucosa-derived decellularized patch can prevent the progression of nasal mucosa injuries to septal perforations. METHODS: Bilateral nasal septal mucosal defects were surgically induced in 36 rabbits. Silastic sheets were applied bilaterally in all rabbits, and decellularized mucosal patch was applied unilaterally (n = 12) or bilaterally (n = 12) at the defect site in the respective experimental groups. Between 1 and 8 weeks postoperatively, the animals were sacrificed, and their nasal septa were completely removed. The excised septa were examined macroscopically and microscopically (histopathological examinations). Moreover, glycosaminoglycan (GAG) estimations of the septa were performed to evaluate mucosal regeneration and mechanical properties. RESULTS: Septal perforations occurred in 5 animals in the control group (5/12; 42%), 1 in the unilateral group (1/12; 9%), and in none in the bilateral group. Compared with the control group, the experimental groups showed significantly different mucosal and cartilage regeneration. CONCLUSION: Decellularized porcine tracheal mucosa can prevent mucosal defects from progressing to septal perforation, promote the repair of mucosal defects, and protect the nasal cartilage.

Dietary factors associated with inflammatory laryngeal disease in South Korea.

Laryngeal inflammation causes not only benign diseases of the larynx, such as laryngitis and granuloma, but also malignancy. Dietary factors are known to control or modulate the inflammatory reaction in the body. To date, the association between laryngeal inflammation and dietary factors has not been reported using nationwide population-based data. The aim of this study was to analyze the association between several dietary factors and inflammatory laryngeal disease in the Korean population. This study analyzed the data from Korean National Health and Nutrition Examination Surveys which is cross-sectional nationwide-population-based study. Association between the dietary nutrient intake and the prevalence of inflammatory laryngeal diseases was analyzed in 21,116 participants who underwent a laryngoscopy and filled in the dietary intake questionnaires. Of the 21,116 participants included in the analysis, 758 (3.59%) were diagnosed with inflammatory laryngeal disease. Prevalence of inflammatory laryngeal disease was higher in men (4.58%) than in women (2.84%). The mean age of patients was 53.77 years. When analyzing the risk using propensity score matching, ILD group tend to consume more coffee and to intake less fiber and iron than normal group. On Logistic regression analysis, an increased intake of carbohydrate, fiber, and iron was associated with lowered risk of having ILD in female. The association between inflammatory laryngeal disease and dietary factors was prominent in the group aged ≥50 years and female. Increased intake of fiber, iron, and vitamin A were associated with lower risk in the group aged ≥50 years. In female, increased intake of fiber, iron were associated with lower risk of having ILD. In the group aged ≤50 years, only an increased consumption of makgeolli, Korean traditional rice wine, was associated with a higher risk of ILD.

Development of Acellular Respiratory Mucosal Matrix Using Porcine Tracheal Mucosa.

BACKGROUND: Respiratory mucosa defects result in airway obstruction and infection, requiring subsequent functional recovery of the respiratory epithelium. Because site-specific extracellular matrix (ECM) facilitates restoration of organ function by promoting cellular migration and engraftment, previous studies considered decellularized trachea an ideal ECM; however, incomplete cell removal from cartilage and mucosal-architecture destruction are frequently reported. Here, we developed a decellularization protocol and applied it to the respiratory mucosa of separated porcine tracheas. METHODS: The trachea was divided into groups according to decellularization protocol: native mucosa, freezing-thawing (FT), FT followed by the use of Perasafe-based chemical agents before mucosal separation (wFTP), after mucosal separation (mFTP), and followed by DNase decellularization (mFTD). Decellularization efficacy was evaluated by DNA quantification and hematoxylin and eosin staining, and ECM content of the scaffold was evaluated by histologic analysis and glycosaminoglycan and collagen assays. Biocompatibility was assessed by cell-viability assay and in vivo transplantation. RESULTS: The mFTP mucosa showed low antigenicity and maintained the ECM to form a proper microstructure. Additionally, tonsil-derived stem cells remained viable when cultured with or seeded onto mFTP mucosa, and the in vivo host response showed a constructive pattern following implantation of the mFTP scaffolds. CONCLUSION: These results demonstrated that xenogenic acellular respiratory mucosa matrix displayed suitable biocompatibility as a scaffold material for respiratory mucosa engineering.

Trends in the Incidence and Treatment of Benign Vocal Fold Lesions in Korea, 2006-2015: A Nationwide Population-based Study.

OBJECTIVE: The aim of this study was to determine the prevalence and demographics of benign vocal fold lesions (BVFL) and trends in its treatment in Korea based on data collected from the National Health Insurance Service database. MATERIAL AND METHODS: Data for patients diagnosed with BVFL (ICM-10 codes J381, J382, J384) from 2006 to 2015 were selected for analysis. Patient characteristics, including sex, age, income, area of residence, and comorbidity, were analyzed. Treatment was divided into surgical management and conservative management using operation codes. RESULTS: The prevalence and incidence of BVFL increased from 7.07% and 5.29%, respectively, in 2006 to 12.47% and 7.98% in 2015. Compared with the non-BVFL population, patients with BVFL were more likely to be female, reside in an urban area, and have gastroesophageal reflux disease. There was no significant change in the incidence of surgical treatment during the study period (around 6000 per year); however, the surgical treatment rate decreased from 19.29% to 8.38%. The probability of undergoing surgical treatment for BVFL was higher in men, those aged 50-59 years, and those in the lowest quartile for income, except for the medical aid group. CONCLUSION: In Korea, there was an increase in the number of patients diagnosed with BVFL and a decrease in the operation rate for this condition between 2006 and 2015. Diagnosis of BVFL varied significantly based on income and sex; however, the only variable affecting the operation rate was patient age.

A 3D-printed polycaprolactone/ß-tricalcium phosphate mandibular prosthesis: A pilot animal study.

OBJECTIVE: In this study, we assessed the effectiveness of a tonsil-derived mesenchymal stem cell (TMSC)-transplanted polycaprolactone/beta-tricalcium phosphate prosthesis (specifically designed for easier fixing and grafting with a single scaffold) on rabbit mandible osteogenesis. METHODS: The mandibles of 18 rabbits were exposed, and 10 × 8-mm bone defects were made. Two rabbits did not receive implants; four were reconstructed with the scaffold control (SC) (SC group); four were reconstructed with scaffolds soaked in peripheral blood (PB) (PB group); four were reconstructed with TMSC-transplanted scaffolds (TMSC group); and four were reconstructed with differentiated osteocyte-transplanted scaffolds (DOC) (DOC group). Each rabbit was sacrificed 12 weeks after surgery, and the area of new bone formation was investigated by mechanical testing, histology, and micro-computed tomography. RESULTS: More extended and denser new bone masses were observed in the TMSC and DOC groups, although fibrosis and vascular formation levels were similar in all groups, suggesting that the dual-structured scaffold alone provides a good environment for bone attachment and regeneration. The bone volumes of representative scaffolds from the SC, PB, TMSC, and DOC groups were 43.12, 48.35, 53.10, and 57.44% of the total volumes, respectively. CONCLUSION: The design of the scaffold resulted in effective osteogenesis, and TMSCs showed osteogenic potency, indicating that their combination could enable effective bone regeneration. LEVEL OF EVIDENCE: NA Laryngoscope, 130:358-366, 2020.

Tonsil-derived stem cells as a new source of adult stem cells.

Located near the oropharynx, the tonsils are the primary mucosal immune organ. Tonsil tissue is a promising alternative source for the high-yield isolation of adult stem cells, and recent studies have reported the identification and isolation of tonsil-derived stem cells (T-SCs) from waste surgical tissue following tonsillectomies in relatively young donors (i.e., under 10 years old). As such, T-SCs offer several advantages, including superior proliferation and a shorter doubling time compared to bone marrow-derived mesenchymal stem cells (MSCs). T-SCs also exhibit multi-lineage differentiation, including mesodermal, endodermal (e.g., hepatocytes and parathyroid-like cells), and even ectodermal cells (e.g., Schwann cells). To this end, numbers of researchers have evaluated the practical use of T-SCs as an alternative source of autologous or allogenic MSCs. In this review, we summarize the details of T-SC isolation and identification and provide an overview of their application in cell therapy and regenerative medicine.

Fabrication and characterization of 3D-printed elastic auricular scaffolds: A pilot study.

OBJECTIVE: Aesthetic reconstruction of the external ear is challenging due to the complex anatomical shape of the auricle. Recently, artificial scaffolds such as Medpor (Stryker, Kalamasoo, MI, USA) have become widely used in ear reconstruction. However, the Medpor scaffold is stiffer than the natural ear, which may lead to discomfort, and moreover has uniform design for every patient. In this study, we investigated whether three-dimensional (3D)-printed artificial polyurethane (PU) scaffolds are suitable for auricular reconstruction. METHODS: PU scaffolds were fabricated using 3D printing according to a design derived from a digital imaging and communications in medicine (DICOM) image of the human auricle. The microstructure of the scaffolds was observed using scanning electron microscopy, and the porosity was examined. Cell proliferation on the scaffolds was assessed in vitro using tonsil-derived mesenchymal stem cells to evaluate the biocompatibility of the scaffolds. The scaffolds were implanted in C57BL/6 mice, and histological analysis was performed. RESULTS: The structural study revealed that the 3D-printed porous PU scaffolds have rectangular microstructure with regular pitch and line, as well as high porosity (56.46% ± 10.22%) with a pore diameter of 200 µm. The mechanical properties of the 3D-printed PU scaffolds were similar to those of the human auricle cartilage. Cell proliferation on the PU scaffolds was greater than that on Medpor scaffolds. Histological evaluation demonstrated that the porous parts of the PU scaffolds became filled with collagen and vascular tissue. CONCLUSION: Elastic, porous PU scaffolds can be obtained using 3D printing, have biomechanical properties similar to those of the natural ear, and are suitable for use in auricular reconstruction. LEVEL OF EVIDENCE: NA Laryngoscope, 129:351-357, 2019.

Feasibility of autologous plasma gel for tonsil-derived stem cell therapeutics in hypoparathyroidism.

Hypoparathyroidism is a deficiency of the parathyroid hormone (PTH) in the body. We previously reported the possibility of treating it using tonsil-derived mesenchymal stem cells (TMSCs) differentiated into PTH-releasing cells. The purpose of this study was to evaluate the feasibility of using autologous plasma gel as scaffold material in treatment of hypoparathyroidism with TMSC. We obtained plasma by venous sampling of autologous blood and centrifuged and fabricated the plasma gel using a sinusoidal pattern heating machine. After we created the hypoparathyroidism animal model, we administered undifferentiated TMSCs and TMSCs differentiated into parathyroid cells at each rat dorsum by intramuscular injection with and without the plasma gel. In the plasma gel groups, intact PTH was detected from on day 21 after TMSC injection; we did not detect intact PTH in the groups that were only transplanted with TMSCs during the entire experimental period. Serum calcium was higher and phosphorous was lower in the TMSC with plasma gel groups than in the groups with TMSCs alone. We detected PTH and chromogranin A in the TMSC-plasma gel-transplanted areas on immunohistochemistry and immunofluorescence stain. Plasma gel can be considered as a cell-delivery scaffold for treating hypoparathyroidism with tonsil-derived mesenchymal stem cells.

Multiplex polymerase chain reaction assays for the detection of the zearalenone chemotype of Fusarium species in white and brown rice.

Early detection of the zearalenone (ZEA) chemotype of Fusarium species could be a precautionary measure for preventing ZEA contamination in rice. In this study, a multiplex polymerase chain reaction (mPCR) assay for detecting ZEA-producing fungi in rice was established using a set of four primers targeting the ZEA biosynthesis genes PKS3, PKS13, ZEB1, and ZEB2. Two mPCR approaches were used: one that amplified the DNA obtained from Fusarium isolates (conventional method) and another that directly amplified the target DNA from rice samples without time-consuming DNA isolation (direct method). The two mPCR methods showed high sensitivity in detecting ZEA-producing species, with a detection limit of 1.25 pg/µL of genomic DNA and 102 and 103 spores/g of white and brown rice, respectively. Both methods were specific for ZEA-producing species and gave four band patterns. The application of the two mPCR methods to 51 Fusarium isolates and 41 rice samples revealed that 31% (16 of 51) and 24% (10 of 41) of the samples were contaminated with ZEA-producing species, respectively. The mPCR results were further evaluated using high-performance liquid chromatography; in general, the two methods yielded similar results. These findings indicate that both mPCR methods are suitable for the detection of ZEA-producing Fusarium species in white and brown rice; however, the direct method yielded more rapid results.

Preventive effects of tonsil-derived mesenchymal stem cells on osteoradionecrosis in a rat model.

BACKGROUND: The purpose of this study was to investigate the effects of tonsil-derived mesenchymal stem cells (MSCs) on osteoradionecrosis (ORN). METHOD: We generated a mandibular ORN rat model using a combination of 20-Gy single-dose irradiation and tooth extraction. Study groups were negative control (tooth extraction only), ORN group (irradiation, tooth extraction), Matrigel-1 group (Matrigel; BD Biosciences, San Jose, CA; irradiation, Matrigel application immediately after tooth extraction), tonsil-derived MSC-1 group (irradiation, tonsil-derived MSC application immediately after tooth extraction), Matrigel-4 group (irradiation, Matrigel application 4 weeks after tooth extraction), and tonsil-derived MSC-4 group (irradiation, tonsil-derived MSC application 4 weeks after tooth extraction). RESULT: Bone mineral density was significantly lower in the ORN group than in the negative control group. The tonsil-derived MSC-1 group showed significantly higher bone mineral density than did the ORN and tonsil-derived MSC-4 groups. CONCLUSION: A single 20-Gy dose of irradiation combined with tooth extraction successfully generated ORN in the rat model. The tonsil-derived MSCs can be effective for bone regeneration in ORN, particularly when applied immediately after dentoalveolar trauma or surgery.

Negative Pressure Pulmonary Hemorrhage after Laryngospasm during the Postoperative Period.

Negative pressure pulmonary hemorrhage (NPPH) is an uncommon complication of upper airway obstruction. Severe negative intrathoracic pressure after upper airway obstruction can increase pulmonary capillary mural pressure, which results in mechanical stress on the pulmonary capillaries, causing NPPH. We report a case of acute NPPH caused by laryngospasm in a 25-year-old man during the postoperative period. Causative factors of NPPH include negative pulmonary pressure, allergic rhinitis, smoking, inhaled anesthetics, and positive airway pressure due to coughing. The patient's symptoms resolved rapidly, within 24 hours, with supportive care.

Laryngeal myofascial pain syndrome as a new diagnostic entity of dysphonia.

OBJECTIVE: To consider the feasibility of diagnosing intrinsic laryngeal muscle myofascial pain syndrome (MPS) in dysphonic patients who demonstrated immediate symptom and stroboscopic finding improvement after laryngeal electromyography (LEMG) without further treatment. METHODS: A chart review of patients who showed subtle vocal fold movement abnormalities on a stroboscopic examination and underwent ultrasonography (US)-guided LEMG was performed. Patients with vocal fold paralysis, mucosal lesions, spasmodic dysphonia, and vocal tremor on stroboscopic examination were excluded. Among them, patients with normal EMG findings were included in this study. The patients who reported voice symptom improvement after LEMG without further treatment were placed in laryngeal MPS (LMPS) group and the other patients were placed in non-laryngeal MPS (non-MPS) group. Predisposing factors, voice symptom, symptom-duration, and stroboscopic findings of these patients were reviewed. RESULTS: Among the 16 patients, LEMG findings were normal, five (31%) were included in the LMPS group and the other 11 patients (69%) were included in the non-MPS group. All LMPS group patients had a history of voice abuse and reported odynophonia. The Korean Voice Handicap Index-10 score decreased significantly after US-guided LEMG without additional treatment in the LMPS group. The stroboscopic findings revealed that vocal fold hypomobility was the most common finding in the LMPS group, and two patients showed a muscle tension dysphonia pattern. The LMPS groups showed improvement of vocal fold mobility on 1-week stroboscopic evaluation. CONCLUSION: LMPS is a potential diagnosis for patients with vocal fold hypomobility finding on stroboscopic findings but with normal EMG results. Diagnosis of LMPS could be considered in patients who showed symptom and vocal fold movement improvement after LEMG.

Standardization of A Physiologic Hypoparathyroidism Animal Model.

Ideal hypoparathyroidism animal models are a prerequisite to developing new treatment modalities for this disorder. The purpose of this study was to evaluate the feasibility of a model whereby rats were parathyroidectomized (PTX) using a fluorescent-identification method and the ideal calcium content of the diet was determined. Thirty male rats were divided into surgical sham (SHAM, n = 5) and PTX plus 0, 0.5, and 2% calcium diet groups (PTX-FC (n = 5), PTX-NC (n = 10), and PTX-HC (n = 10), respectively). Serum parathyroid hormone levels decreased to non-detectable levels in all PTX groups. All animals in the PTX-FC group died within 4 days after the operation. All animals survived when supplied calcium in the diet. However, serum calcium levels were higher in the PTX-HC than the SHAM group. The PTX-NC group demonstrated the most representative modeling of primary hypothyroidism. Serum calcium levels decreased and phosphorus levels increased, and bone volume was increased. All animals survived without further treatment and did not show nephrotoxicity including calcium deposits. These findings demonstrate that PTX animal models produced by using the fluorescent-identification method, and fed a 0.5% calcium diet, are appropriate for hypoparathyroidism treatment studies.

3D printed polyurethane prosthesis for partial tracheal reconstruction: a pilot animal study.

A ready-made, acellular patch-type prosthesis is desirable in repairing partial tracheal defects in the clinical setting. However, many of these prostheses may not show proper biological integration and biomechanical function when they are transplanted. In this study, we developed a novel 3D printed polyurethane (PU) tracheal scaffold with micro-scale architecture to allow host tissue infiltration and adequate biomechanical properties to withstand physiological tracheal condition. A half-pipe shaped PU scaffold (1.8 cm of height, 0.18 cm thickness, and 2 cm of diameter) was fabricated by 3D printing of PU 200 µm PU beam. The 3D printed tracheal scaffolds consisted of a porous inner microstructure with 200 × 200 × 200 µm3 sized pores and a non-porous outer layer. The mechanical properties of the scaffolds were 3.21 ± 1.02 MPa of ultimate tensile strength, 2.81 ± 0.58 MPa of Young's modulus, and 725% ± 41% of elongation at break. To examine the function of the 3D printed tracheal scaffolds in vivo, the scaffolds were implanted into 1.0 × 0.7 cm2 sized anterior tracheal defect of rabbits. After implantation, bronchoscopic examinations revealed that the implanted tracheal scaffolds were patent for a 16 week-period. Histologic findings showed that re-epithelialization after 4 weeks of implantation and ciliated respiratory epithelium with ciliary beating after 8 weeks of implantation were observed at the lumen of the implanted tracheal scaffolds. The ingrowth of the connective tissue into the scaffolds was observed at 4 weeks after implantation. The biomechanical properties of the implanted tracheal scaffolds were continually maintained for 16 week-period. The results demonstrated that 3D printed tracheal scaffold could provide an alternative solution as a therapeutic treatment for partial tracheal defects.