Bifunctional Tumor-Targeted Bioprobe for Phothotheranosis.

Background: Near-infrared (NIR) phototheranostics provide promising noninvasive imaging and treatment for head and neck squamous cell carcinoma (HNSCC), capitalizing on its adjacency to skin or mucosal surfaces. Activated by laser irradiation, targeted NIR fluorophores can selectively eradicate cancer cells, harnessing the power of synergistic photodynamic therapy and photothermal therapy. However, there is a paucity of NIR bioprobes showing tumor-specific targeting and effective phototheranosis without hurting surrounding healthy tissues. Methods: We engineered a tumor-specific bifunctional NIR bioprobe designed to precisely target HNSCC and induce phototheranosis using bioconjugation of a cyclic arginine-glycine-aspartic acid (cRGD) motif and zwitterionic polymethine NIR fluorophore. The cytotoxic effects of cRGD-ZW800-PEG were measured by assessing heat and reactive oxygen species (ROS) generation upon an 808-nm laser irradiation. We then determined the in vivo efficacy of cRGD-ZW800-PEG in the FaDu xenograft mouse model of HNSCC, as well as its biodistribution and clearance, using a customized portable NIR imaging system. Results: Real-time NIR imaging revealed that intravenously administered cRGD-ZW800-PEG targeted tumors rapidly within 4 h postintravenous injection in tumor-bearing mice. Upon laser irradiation, cRGD-ZW800-PEG produced ROS and heat simultaneously and exhibited synergistic photothermal and photodynamic effects on the tumoral tissue without affecting the neighboring healthy tissues. Importantly, all unbound bioprobes were cleared through renal excretion. Conclusions: By harnessing phototheranosis in combination with tailored tumor selectivity, our targeted bioprobe ushers in a promising paradigm in cancer treatment. It promises safer and more efficacious therapeutic avenues against cancer, marking a substantial advancement in the field.

Fluidic integrated 3D bioprinting system to sustain cell viability towards larynx fabrication.

Herein, we report the first study to create a three-dimensional (3D) bioprinted artificial larynx for whole-laryngeal replacement. Our 3D bio-printed larynx was generated using extrusion-based 3D bioprinter with rabbit's chondrocyte-laden gelatin methacryloyl (GelMA)/glycidyl-methacrylated hyaluronic acid (GMHA) hybrid bioink. We used a polycaprolactone (PCL) outer framework incorporated with pores to achieve the structural strength of printed constructs, as well as to provide a suitable microenvironment to support printed cells. Notably, we established a novel fluidics supply (FS) system that simultaneously supplies basal medium together with a 3D bioprinting process, thereby improving cell survival during the printing process. Our results showed that the FS system enhanced post-printing cell viability, which enabled the generation of a large-scale cell-laden artificial laryngeal framework. Additionally, the incorporation of the PCL outer framework with pores and inner hydrogel provides structural stability and sufficient nutrient/oxygen transport. An animal study confirmed that the transplanted 3D bio-larynx successfully maintained the airway. With further development, our new strategy holds great potential for fabricating human-scale larynxes with in vivo-like biological functions for laryngectomy patients.

Anti-inflammatory and Anti-bacterial Effects of Allicin-coated Tracheal Tube on Trachea Mucosa.

BACKGROUND/AIM: Allicin has been known to improve wound healing via antimicrobial and anti-inflammatory properties. The aim of this study was to evaluate whether an allicin-coated tracheal tube can prevent tracheal stenosis through improving wound healing after tracheal injury. MATERIALS AND METHODS: Allicin-coated silicone tracheal tube (t-tube) was prepared by the polydopamine-mediated coating method. Tracheal mucosa was injured, and an allicin-coated t-tube was placed into the trachea to evaluate mucosal changes until designated time point. Anti-inflammatory, anti-bacterial and cytotoxic effects of allicin were also investigated in in vitro. RESULTS: Allicin- coated silicone was not cytotoxic, and it showed anti-inflammatory and anti-bacterial effects in in vitro analysis. The use of allicin-coated t-tube in a rabbit model showed favorable mucosal healing with significant decrease of proinflammatory cytokines compared to the non-coated tube group. The allicin-coated tube showed obvious decreased number of cocci-shaped bacterial attached to the tube surface. From the histological point of view, the allicin- coated tube showed faster regeneration of the normal respiratory epithelial structure compared to the non-coated group. CONCLUSION: Allicin-coated t-tube showed anti-inflammatory and anti-bacterial effects on injured tracheal mucosa. We suggest that allicin-coated t-tube can be used for promoting physiological wound healing to prevent laryngotracheal stenosis.

Comparison of intradialytic blood pressure metrics as predictors of all-cause mortality.

BACKGROUND: Intradialytic hypotension (IDH) has been reported to be an important prognostic factor in hemodialysis patients. However, a standard definition of IDH has not yet been determined. METHODS: We retrospectively analyzed blood pressure (BP) metrics obtained during serial dialysis sessions over a 90-day period from a single dialysis center from 2016 to 2017. The mean values and the frequency of specific values of BP were analyzed as predictors of 3-year mortality. RESULTS: A total of 430 patients who underwent maintenance dialysis were included. The mean age was 63.3 ± 12.4 years and 58.6% were male. A low minimum systolic blood pressure (SBP) <110 mmHg during dialysis was significantly associated with increased all-cause mortality. The frequency of a minimum SBP <100 mmHg was the most significant predictor of 3-year mortality, with an area under the curve (AUC) of 0.722. Furthermore, the frequency of a minimum SBP <100 mmHg significantly increased the predictability of mortality when combined with the presence of other clinical factors including age, body mass index and vascular access type (AUC 0.786 vs. 0.835; p = 0.005). CONCLUSION: Among the various intradialytic BP metrics, the frequency of a minimum SBP <100 mmHg is the most significant factor related to all-cause mortality. The guidelines for the management of blood pressure in dialysis patients should consider including a minimum SBP <100 mmHg as a definition for IDH.

3D bioprinted silk fibroin hydrogels for tissue engineering.

The development of biocompatible and precisely printable bioink addresses the growing demand for three-dimensional (3D) bioprinting applications in the field of tissue engineering. We developed a methacrylated photocurable silk fibroin (SF) bioink for digital light processing 3D bioprinting to generate structures with high mechanical stability and biocompatibility for tissue engineering applications. Procedure 1 describes the synthesis of photocurable methacrylated SF bioink, which takes 2 weeks to complete. Digital light processing is used to fabricate 3D hydrogels using the bioink (1.5 h), which are characterized in terms of methacrylation, printability, mechanical and rheological properties, and biocompatibility. The physicochemical properties of the bioink can be modulated by varying photopolymerization conditions such as the degree of methacrylation, light intensity, and concentration of the photoinitiator and bioink. The versatile bioink can be used broadly in a range of applications, including nerve tissue engineering through co-polymerization of the bioink with graphene oxide, and for wound healing as a sealant. Procedure 2 outlines how to apply 3D-printed SF hydrogels embedded with chondrocytes and turbinate-derived mesenchymal stem cells in one specific in vivo application, trachea tissue engineering, which takes 2-9 weeks.

Urine and Serum Electrolytes and Biochemical Values Associated with Osteoporosis in Premenopausal and Postmenopausal Women: A Longitudinal and Cross-Sectional Study Using Korean Genome and Epidemiology Study (KoGES) Cohort.

Osteoporosis is a major public health concern, especially in women. This study aims to identify early biomarkers from biochemical measurements of serum and urine for recognizing the development of osteoporosis and osteopenia in premenopausal and postmenopausal women. From the Korean Genome and Epidemiology Study (KoGES) cohort, longitudinal study participants with normal bone density were enrolled and assessed for the association of baseline clinical and biochemical factors with osteoporosis development over 4 years. In addition, a cross-sectional study between normal bone density and osteopenia/osteoporosis was conducted to validate the risk factors found in the longitudinal cohort. Of the 5272 female participants in the KoGES cohort, 813 women (501 premenopausal and 312 menopausal) who had normal bone density at baseline were included in the longitudinal study. During the 4 years of follow-up, 64 patients developed osteoporosis and 354 developed osteopenia. In a multivariate logistic regression analysis, serum calcium and urine uric acid levels were significantly associated with elevated osteoporosis risk in premenopausal and postmenopausal women, respectively (risk of osteoporosis by serum calcium levels in premenopausal women: 4.03 (1.09-14.93), p = 0.037; risk of osteoporosis by urine uric acid levels in postmenopausal women: 24.08 (1.79-323.69), p = 0.016). For the cross-sectional study, serum and urine parameters were compared between women with osteopenia or osteoporosis at baseline and those with normal bone density. Urine uric acid levels were found to be significantly higher in both premenopausal and postmenopausal women with bone loss than in women with normal bone density (p < 0.001 and p = 0.004, respectively). Uric acid level in urine may be an early marker for the development of osteoporosis in women, especially after menopause.

Therapeutic Effects of Tonsil-derived Mesenchymal Stem Cells in an Atopic Dermatitis Mouse Model.

BACKGROUND/AIM: Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in atopic dermatitis. Palatine tonsils are lymphoepithelial tissue located around the oropharynx and have been proposed as one of the important alternative sources of MSCs. The purpose of this study was to evaluate the protective and therapeutic effects of tonsil-derived MSCs (TMSCs) in a 2,4-dinitrofluorobenzene (DNFB)-induced mouse model of atopic dermatitis (AD). MATERIALS AND METHODS: The effect of TMSCs was evaluated in 20 C57BL/6J mice that were randomly divided into four groups (normal, DNFB-PBS, DNFB-TMSC7, and DNFB-TMSC16 group). TMSCs were subcutaneously injected into DNFB-sensitized mice on day 7 (DNFB-TMSC7 group) and day 16 (DNFB-TMSC16 group). Several parameters of inflammation were assessed. RESULTS: Subcutaneously injected TMSCs significantly improved the inflammatory symptoms in a DNFB-induced AD model mice, particularly showing therapeutic effects rather than protective effects. TMSC treatment inhibited T-cell-mediated inflammatory responses by decreasing the levels of IL-6, IL-1ß, TNF-α (Th1 cell marker), IL-4 (Th2 cell marker), and B-cell-mediated serum IgE. In contrast, TMSCs enhanced the anti-inflammatory cytokine TGF-ß. CONCLUSION: In vitro and in vivo results suggest that TMSC treatment improved inflammatory skin lesions in the DNFB-induced AD mice model via immunomodulatory effects of the TMSCs. TMSCs inhibit T-cell and B-cell mediated responses, and enhance the anti-inflammatory responses.

Safety of drainless excision of the submandibular gland / Segurança na excisão da glândula submandibular sem o uso de drenos

Abstract Introduction: Percutaneous drains can be associated with several complications, including infection, fistula formation, discomfort and prolonged hospitalization. Objective: The aim of this study was to evaluate the safety of submandibular gland excision without the use of surgical drains. Methods: We analyzed the surgery time, postoperative complications such as bleeding, facial palsy, seroma, and repeat exploration of wounds and duration of the hospital stay. Excision of the submandibular gland via a transcervical approach was undertaken by two surgeons. Prior to wound closure, the skin flap and wound bed were approximated using hemostatic fibrin glue (Greenplast-Q PFS KIT®, GC Greencross, Youngin, Korea). Neither saline irrigation nor insertion of a percutaneous drain were included. Results: A total of 23 patients underwent submandibular gland excision. The study group consisted of 14 men (60.8%) and 9 women (39.2%) (mean age, 47.6 years; range, 24-70 years). There were two patients who had minor complications. One patient showed minor bleeding on the skin incision line immediately postoperatively, and one developed a seroma at 7 days postoperatively. There were no major surgical complications. Total duration of the surgery from skin incision to closure averaged 44.86 minutes. Mean duration of the hospital stay was 3.17 days. Patients were discharged on average at 1.17 days after surgery. Conclusion: The submandibular gland can be safely excised without the use of a surgical drain, therefore allowing early patient discharge.

Resumo Introdução: Os drenos percutâneos apresentam várias complicações associadas, inclusive infecção, formação de fístulas, desconforto e permanência hospitalar prolongada. Objetivo: Avaliar a segurança da excisão da glândula submandibular sem o uso de drenos cirúrgicos. Método: Analisamos o tempo de cirurgia, as complicações pós-operatórias tais como sangramento, paralisia facial, seroma e necessidade de reexploração de ferida operatória, e a duração da internação hospitalar. A excisão da glândula submandibular por via transcervical foi realizada por dois cirurgiões. Antes do fechamento da incisão, o retalho cutâneo e o leito da ferida operatória foram aproximados utilizando cola hemostática de fibrina (Greenplast-Q PFS KIT®, GC Greencross, Youngin, República da Coréia). Não houve irrigação salina nem uso de dreno percutâneo. Resultados: Foram submetidos 23 pacientes à excisão da glândula submandibular. O grupo de estudo consistiu em 14 homens (60,8%) e 9 mulheres (39,2%) (média de 47,6 anos; variação de 24 a 70). Dois pacientes apresentaram complicações menores. Um paciente apresentou pequeno sangramento na incisão da pele no pós-operatório imediato e um deles teve seroma aos 7 dias de pós-operatório. Não houve complicações cirúrgicas importantes. A duração total da cirurgia, desde a incisão na pele até o fechamento, foi de 44,86 minutos. A duração média da internação hospitalar foi de 3,17 dias. Os pacientes receberam alta em média 1,17 dia após a cirurgia. Conclusão: A glândula submandibular pode ser excisada com segurança sem o uso de dreno cirúrgico, permitindo que o paciente tenha alta hospitalar mais precocemente.

4D-bioprinted silk hydrogels for tissue engineering.

Recently, four-dimensional (4D) printing is emerging as the next-generation biofabrication technology. However, current 4D bioprinting lacks biocompatibility or multi-component printability. In addition, suitable implantable targets capable of applying 4D bioprinted products have not yet been established, except theoretical and in vitro study. Herein, we describe a cell-friendly and biocompatible 4D bioprinting system including more than two cell types based on digital light processing (DLP) and photocurable silk fibroin (Sil-MA) hydrogel. The shape changes of 3D printed bilayered Sil-MA hydrogels were controlled by modulating their interior or exterior properties in physiological conditions. We used finite element analysis (FEA) simulations to explore the possible changes in the complex structure. Finally, we made trachea mimetic tissue with two cell types using this 4D bioprinting system and implanted it into a damaged trachea of rabbit for 8 weeks. The implants were integrated with the host trachea naturally, and both epithelium and cartilage were formed at the predicted sites. These findings demonstrate that 4D bioprinting system could make tissue mimetic scaffold biologically and suggest the potential value of the 4D bioprinting system for tissue engineering and the clinical application.

A 3D Printable Electroconductive Biocomposite Bioink Based on Silk Fibroin-Conjugated Graphene Oxide.

Reduced graphene oxide (rGO) has wide application as a nanofiller in the fabrication of electroconductive biocomposites due to its exceptional properties. However, the hydrophobicity and chemical stability of rGO limit its ability to be incorporated into precursor polymers for physical mixing during biocomposite fabrication. Moreover, until now, no suitable rGO-combining biomaterials that are stable, soluble, biocompatible, and 3D printable have been developed. In this study, we fabricated digital light processing (DLP) printable bioink (SGOB1), through covalent reduction of graphene oxide (GO) by glycidyl methacrylated silk fibroin (SB). Compositional analyses showed that SGOB1 contains approximately 8.42% GO in its reduced state. Our results also showed that the rGO content of SGOB1 became more thermally stable and highly soluble. SGOB1 hydrogels demonstrated superior mechanical, electroconductive, and neurogenic properties than (SB). Furthermore, the photocurable bioink supported Neuro2a cell proliferation and viability. Therefore, SGOB1 could be a suitable biocomposite for neural tissue engineering.

A Feasibility Study for 3D-printed Poly(methyl methacrylate)-resin Tracheostomy Tube Using a Hamster Cheek Pouch Model.

BACKGROUND/AIM: A three-dimensional (3D) printed tracheostomy tube has potential application for patients who require a specialized tube. The aim of this study was to evaluate the characteristics of various 3D printing materials and determine their use in producing 3D-printed tracheostomy tube. MATERIALS AND METHODS: Mechanical, chemical, and microbiological in vivo changes in the scaffolds were analyzed using a hamster cheek pouch (HCP) model. RESULTS: The poly methyl methacylate (PMMA)-resin showed superior pre- and post-insertion mechanical properties and a relatively consistent lower biofilm formation compared with other scaffolds. PMMA-resin was successfully 3D-printed with dimensional accuracy without a support system. The use of a 3D-printed PMMA tracheostomy tube in a rabbit trachea showed no definite signs of infection, allergy or foreign body reaction. CONCLUSION: PMMA-resin can be proposed as an alternative for a 3D-printed tracheostomy tube material. In addition, we suggest HCPs as an in vivo model for evaluating indwelling medical devices.

Wound Healing Promoting Activity of Tonsil-Derived Stem Cells on 5-Fluorouracil-Induced Oral Mucositis Model.

BACKGROUND: We first determined the efficacy of lesional injection of tonsil-derived MSCs (mesenchymal stem cells) for the treatment of 5-fluorouracil induced oral mucositis. METHODS: Oral mucositis was induced in hamsters by administration of 5-fluorouracil (day 0, 2, 4) followed by mechanical trauma (day 1, 2, 4). The experimental groups included MT (mechanical trauma only), 5-FU + MT (mechanical trauma with 5-fluorouracil administration), TMSC (mechanical trauma with 5-fluorouracil administration, tonsil-derived mesenchymal stem cells injection), DEXA (mechanical trauma with 5-fluorouracil administration, dexamethasone injection), and saline (mechanical trauma with 5-fluorouracil administration, saline injection). RESULTS: On day 10, gross and histologic analyses showed that nearly complete healing and epithelialization of the cheek mucosa of the TMSC group, whereas the other groups showed definite ulcerative lesions. Compared with the MT and DEXA groups, CD31 expression was greater in the TMSC group on days 10 and 14. Tendency towards a decrease in MMP2 expression with the time in the TMSC group was observed. In addition, the TMSC group showed higher expression of TGF-ß, and NOX4 on day 10 compared with the other groups. Scratch assay demonstrated that the conditioned media harvested from tonsil-derived MSCs significantly increased migratory efficacy of NIH3T3 cells. Transwell assay showed that the preferential migration of tonsil-derived MSCs to the wound area. CONCLUSION: Intralesional administration of tonsil-derived MSCs may accelerate wound healing of 5-fluorouracil induced oral mucositis by upregulating neovascularization and effective wound contraction. In addition, tonsil-derived MSCs might contribute to oral ulcer regeneration via the stimulation of fibroblast proliferation and migration.

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.

Safety of drainless excision of the submandibular gland.

INTRODUCTION: Percutaneous drains can be associated with several complications, including infection, fistula formation, discomfort and prolonged hospitalization. OBJECTIVE: The aim of this study was to evaluate the safety of submandibular gland excision without the use of surgical drains. METHODS: We analyzed the surgery time, postoperative complications such as bleeding, facial palsy, seroma, and repeat exploration of wounds and duration of the hospital stay. Excision of the submandibular gland via a transcervical approach was undertaken by two surgeons. Prior to wound closure, the skin flap and wound bed were approximated using hemostatic fibrin glue (Greenplast-Q PFS KIT®, GC Greencross, Youngin, Korea). Neither saline irrigation nor insertion of a percutaneous drain were included. RESULTS: A total of 23 patients underwent submandibular gland excision. The study group consisted of 14 men (60.8%) and 9 women (39.2%) (mean age, 47.6 years; range, 24-70 years). There were two patients who had minor complications. One patient showed minor bleeding on the skin incision line immediately postoperatively, and one developed a seroma at 7 days postoperatively. There were no major surgical complications. Total duration of the surgery from skin incision to closure averaged 44.86minutes. Mean duration of the hospital stay was 3.17 days. Patients were discharged on average at 1.17 days after surgery. CONCLUSION: The submandibular gland can be safely excised without the use of a surgical drain, therefore allowing early patient discharge.

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.

Comparing the Superficial Vasculature of the Central Nervous System in Six Laboratory Animals: A Hypothesis About the Role of the "Circle of Willis".

We provide images of the entire central nervous system vasculature, and compare the anatomical findings in six different laboratory animals. A detailed understanding of the specific anatomy for each is important in the design of experimental modeling and for understanding the specific function of each target organ. Six different types of animals, the Korean wild mouse, C57BL/6J mouse, F344 rat, mongolian gerbil, Syrian hamsters, and guinea pigs, were included. To stain the blood vessels in each of the animals, Alcian blue reagent was used to perfuse each species. The bifurcation and anastomotic patterns of the anterior cerebral arteries differed in each species. The vascular supply to the olfactory nerve was visualized as a single artery supplying both olfactory nerves, and arteries supplying the lateral portion of the olfactory nerves originating from the olfactory bulb area. The posterior communicating arteries of the six animals demonstrated unique morphologies. The shape of the hypophyseal portal system varied by species. Most animals used in this study had a hexagonal Circle of Willis, except for the Korean wild mouse. Using this approach, we successfully mapped the brain vascular system in six different species of animals. This information and the images created can guide other researchers as they design research studies and create experimental models for new surgical procedures and approaches. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 302:2049-2061, 2019. © 2019 American Association for Anatomy.

Applicability of vital staining and tissue clearing to vascular anatomy and melanocytes' evaluation of temporal bone in six laboratory species.

The purpose of the present study was to define the applicability of tissue clearing to the field of otology. We combined tissue clearing with vital staining perfusion via a pumping system to examine the vascular anatomy of temporal bones in laboratory animals. We used six different types of species including Korean wild mouse, mouse, Mongolian gerbil, hamsters and Guinea pigs. A mixture of Alcian blue reagent and 4% paraformaldehyde was circulated throughout the entire circulatory system of the animal via a perfusion pump system. Transparency images were obtained from the temporal bones according to the protocol of the SunHyun 3D Imaging Kit. In examining the inner surface of the tympanic membrane, flaccid part (pars flaccida) was positioned along the entire marginal area in Guinea pig. In the Guinea pig, unlike the other species, the cortical bone of the mastoid (bullae) was easily removed using cold instruments, allowing a direct approach to the enclosed structures. The distribution and pattern of cochlea melanocytes were compared among the species. "Mobius strip"-like accumulated melanocytes in vestibules were shown in both the Korean wild mouse and mouse. The collateral blood supply to the cochlea in six different species was checked in various pattern. Combining dye infusion with tissue-clearing techniques, we documented the middle ear and transparent inner ear structures in six different species. The information and associated images will help other researchers to develop hypotheses and design experimental investigations.

An omentum-cultured 3D-printed artificial trachea: in vivo bioreactor.

The purpose of this study was to evaluate whether the prior implantation of a 3D-printed polycaprolactone (PCL) artificial trachea in the omentum is beneficial for revascularization of the scaffold and reduces associated complications in the reconstruction of a circumferential tracheal defect. Ten New Zealand rabbits were divided into 2 groups: (1) PCL-OC group (PCL scaffold cultured in omentum for 2 weeks before transplantation) and (2) PCL group. In the PCL-OC group, newly formed connective tissue completely covered the luminal surface of the scaffold with mild inflammation at 2 weeks postoperatively; a minor degree of stenosis was noted at 8 weeks postoperatively. The PCL group showed scaffold exposure without any tissue regeneration at 2 weeks postoperatively, and a moderate degree of luminal stenosis 6 weeks after implantation. Histology revealed highly organized regenerated tissue composed of ciliated respiratory epithelium, and submucosal layer in the PCL-OC group. Neo-cartilage regeneration was noted in part of the regenerated tissue. The PCL group demonstrated severe inflammation and an unorganized structure compared to that of the PCL-OC group. In vivo omentum culture of the tracheal scaffold before transplantation is beneficial for rapid re-epithelialization and revascularization of the scaffold. It also prevents postoperative luminal stenosis.

New fabrication method of silk fibroin plate and screw based on a centrifugal casting technique.

Recently, a newer generation of absorbable biomaterials has been developed from silk. Silk is approved by the US Food and Drug Administration, has robust mechanical features, and is biocompatible. Moreover, it offers the ability to be functionalized with bioactive compounds, making it ideal for use in new medical devices. Thus, many researchers have considered that absorbable devices made from silk may be able to overcome current limitations and could be used to meet a broader range of fixation needs. Here, we describe a novel method for the fabrication of silk fibroin (SF)-based bioabsorbable fixation systems using a centrifugal casting technique and incorporating a 3D printer. This approach allows us to create the desired geometric design for the fixation system easily. Moreover, our products demonstrated smoother surface profiles and more homogenous and dense cross-sectional architectures. Furthermore, our plates exhibited very similar mechanical properties compared with commercially used one, and our screws showed more than 70% of their initial mass after 7 weeks on the enzymatic degradation test. On in vivo analysis, we found that our devices were well-maintained in the location of initial fixation, and new bone formation was also observed around this. By these results, we suggest that the SF-based plate/screw prepared by our novel method might be used for the internal fixation of fracture sites.

A 4-Axis Technique for Three-Dimensional Printing of an Artificial Trachea.

BACKGROUND: Several types of three-dimensional (3D)-printed tracheal scaffolds have been reported. Nonetheless, most of these studies concentrated only on application of the final product to an in vivo animal study and could not show the effects of various 3D printing methods, materials, or parameters for creation of an optimal 3D-printed tracheal scaffold. The purpose of this study was to characterize polycaprolactone (PCL) tracheal scaffolds 3D-printed by the 4-axis fused deposition modeling (FDM) method and determine the differences in the scaffold depending on the additive manufacturing method. METHODS: The standard 3D trachea model for FDM was applied to a 4-axis FDM scaffold and conventional FDM scaffold. The scaffold morphology, mechanical properties, porosity, and cytotoxicity were evaluated. Scaffolds were implanted into a 7 × 10-mm artificial tracheal defect in rabbits. Four and 8 weeks after the operation, the reconstructed sites were evaluated by bronchoscopic, radiological, and histological analyses. RESULTS: The 4-axis FDM provided greater dimensional accuracy and was significantly closer to CAD software-based designs with a predefined pore size and pore interconnectivity as compared to the conventional scaffold. The 4-axis tracheal scaffold showed superior mechanical properties. CONCLUSION: We suggest that the 4-axis FDM process is more suitable for the development of an accurate and mechanically superior trachea scaffold.