Graphene Hybrid Inner Ear Organoid with Enhanced Maturity.

Inner ear organoids (IEOs) are 3D structures grown in vitro, which can mimic the complex cellular structure and function of the inner ear. IEOs are potential solutions to problems related to inner ear development, disease modeling, and drug delivery. However, current approaches in generating IEOs using chemical factors have a few limitations, resulting in unpredictable outcomes. In this study, we propose the use of nanomaterial-based approaches, specifically by using graphene oxide (GO). GO's unique properties promote cell-extracellular matrix interactions and cell-cell gap junctions, thereby enhancing hair cell formation, which is an essential part of IEO development. We also investigated the potential applications for drug testing. Our findings suggest that GO is a promising candidate for enhancing the functionality of IEOs and advancing our understanding of the problems underlying inner ear development. The use of nanomaterial-based approaches may provide a more reliable and effective method for building better IEOs in the future.

Development of the multi-directional ablation process using the femtosecond laser to create a pattern on the lateral side of a 3D microstructure.

Two-photon stereolithography (TPS) is widely used for the fabrication of various three-dimensional (3D) structures with sub-micron fabrication resolution in a single fabrication process. However, TPS is unsuitable for microstructures with fine-hole patterns. The laser ablation process can be easily drilled, or made holes in various materials. However, in the case of laser ablation, the focal plane of the laser is fixed, which is limited to the processing plane. In this study, a multidirectional ablation process is studied to apply laser ablation to various processing planes of a 3D microstructure fabricated by the TPS process. A 3D hybrid fabrication process with the advantages of both TPS and laser ablation is expected to improve the fabrication efficiency. The 3D hybrid process is proposed based on a single laser source. The microstructure is fabricated using TPS, and the multi-directional ablation process creates a hole in the lateral side of the 3D microstructure. To develop the multidirectional ablation process, the reflecting mirror system should be designed to adaptably rotate the laser focal plane and guide the laser path for the target process plane. Through various examples, we demonstrate the ability of the multi-directional ablation process with various examples.

Design and evaluation of additive manufactured highly efficient inclined-wing type continuous mixer.

We develop a novel milli-scale mixer (tilted-wings mixing unit, TWM unit) based on the design for additive manufacturing (DfAM). The proposed tilted-wings mixer has basically designed to have three separate wings that split and combine fluids in order to mix together effectively. Its structure is simple for easy fabrication: two major design parameters of angle among three wings and connecting angle between tilted-unit, which are optimized using the computational fluid dynamics (CFD) analysis. From the CFD analysis, we obtain the best-combined mixing module from analyses of various combinations of TWM units for a highly effective mixing ratio. The mixing ratio of three combined units reaches near 100%, which is validated by the experiment and analysis. We believe that the proposed milli-scale mixer can be utilized in diverse chemical continuous mixers and reactors for minimizing of use of chemicals that can pollute the environment.

Sequential process optimization for a digital light processing system to minimize trial and error.

In additive manufacturing, logical and efficient workflow optimization enables successful production and reduces cost and time. These attempts are essential for preventing fabrication problems from various causes. However, quantitative analysis and integrated management studies of fabrication issues using a digital light processing (DLP) system are insufficient. Therefore, an efficient optimization method is required to apply several materials and extend the application of the DLP system. This study proposes a sequential process optimization (SPO) to manage the initial adhesion, recoating, and exposure energy. The photopolymerization characteristics and viscosity of the photocurable resin were quantitatively analyzed through process conditions such as build plate speed, layer thickness, and exposure time. The ability of the proposed SPO was confirmed by fabricating an evaluation model using a biocompatible resin. Furthermore, the biocompatibility of the developed resin was verified through experiments. The existing DLP process requires several trials and errors in process optimization. Therefore, the fabrication results are different depending on the operator's know-how. The use of the proposed SPO enables a systematic approach for optimizing the process conditions of a DLP system. As a result, the DLP system is expected to be more utilized.

The effect of 3-D printed polylactic acid scaffold with and without hyaluronic acid on bone regeneration.

BACKGROUND: Three- dimensional (3D) technology has been suggested to overcome several limitations in guided bone regeneration (GBR) procedures because 3D-printed scaffolds can be easily molded to patient-specific bone defect site. This study aimed to investigate the effect of 3-D printed polylactic acid (PLA) scaffolds with or without hyaluronic acid (HA) in a rabbit calvaria model. METHODS: A calvaria defect with a diameter of 15 mm was created in 30 New Zealand white rabbits. The rabbits were randomly allocated into three groups including no graft group (control, n = 10), 3D printed PLA graft group (3D-PLA, n = 10), and 3D printed PLA with hyaluronic acid graft group (3D-PLA/HA, n = 10). Five animals in each group were sacrificed at 4 and 12 weeks after surgery. Microcomputed tomography and histologic and histomorphometric analyses were performed. RESULTS: Over the whole examination period, no significant adverse reactions were observed. There were no statistically significant differences in bone volume (BV) /tissue volume (TV) among the three groups at 4 weeks. However, the highest BV/TV was observed in the 3D-PLA/HA group at 12 weeks. The new bone area for control, 3D-PLA, and 3D-PLA/HA showed no statistical differences at 4 weeks. However, the value was significantly higher in the 3D-PLA and 3D-PLA/HA groups compared to the control group at 12 weeks. CONCLUSION: The 3D printed PLA scaffolds was biocompatible and integrated well with bone defect margin. They were also provided the proper space for new bone formation. Therefore, 3D printed PLA/HA might be a potential tool to enhance bone augmentation.

Optimization of the Projection Microstereolithography Process for a Photocurable Biomass-Based Resin.

Biomass materials, an important source of chemical feedstocks, could replace fossil fuels as a resource in the future. The chemical feedstocks from biomass materials are used in many medical and pharmaceutical products and in fuels, chemicals, and functional materials. Biomass materials are expected to be used in biomedical engineering fields, especially due to their low biotoxicity. By the way, most of the demand for bio-application fields is an application targeted for customized production, so a high formability is required for production. Research on three-dimensional (3D) printing technology capable of satisfying these requirements has been ongoing. Manufacturing additives need to be investigated to use biomass materials as a resin or bioink safely for 3D printing, which is a technique widely used in biomedical engineering fields. In this study, a projection microstereolithography (PµSL) system, a 3D printing technique, was made that uses a biomass-based resin. Biomass materials are designed to be photocurable for use in the PµSL process. Various PµSL process parameters were investigated using the biomass-based resin to determine the optimum fabrication conditions for 3D structures. This study demonstrated that a biomass-based resin can be used in the PµSL process. We provide a method for its application in various biomedical engineering fields.

Additive manufacturing of the core template for the fabrication of an artificial blood vessel: the relationship between the extruded deposition diameter and the filament/nozzle transition ratio.

An artificial blood vessel with a tubular structure was additively manufactured via fused deposition modeling (FDM) starting from a single strand of polyvinyl alcohol (PVA) filament coated with a specific thickness of biocompatible polydimethylsiloxane (PDMS), followed by removal of the inner core via hydrogen peroxide leaching under sonication. In particular, we examined the relationship between the extruded deposition diameter and the filament migration speed/nozzle control speed (referred to as the filament/nozzle transition ratio), which is almost independent of the extruded deposition flow rate due to the weak die-swelling and memory effects of the extruded PVA arising from its intrinsically low viscoelasticity. The chemical stability of the PDMS during sonication in the hydrogen peroxide solution was then determined by spectroscopic techniques. The PDMS displayed no mechanical degradation in the hydrogen peroxide solution, resulting in similar fracture elongation and yield strength to those of the pristine specimen without the leaching treatment. As a further advantage, the inside surface of the PDMS was smooth regardless of the hydrogen peroxide leaching under sonication. The potential application of the as-developed scaffold in soft tissue engineering (particularly that involving vascular tissue regeneration) was demonstrated by the successful transplantation of the artificial blood vessel in a right-hand surgical replica used in a clinical simulation.

Simulative design in macroscale for prospective application to micro-catheters.

In this paper, a motion-transforming element is applied to the development of a new catheter device. The motion-transforming element structure allows a reduction of linear movement and converts linear movement to rotational movement. The simulative design of micro-catheters is based on a proposed structure called the Operating Mini Station (OMS). OMS is operated by movement of a motion-transforming element. A new motion-transforming element is designed using multiple links that are connected by hinged joints based on an elastic design. The design of the links and the hinges are optimized for precise and reliable movement of the motion-transforming element. Because of the elastic design, it is possible to realize a catheter that allows various movements in small spaces like capillaries.

3D Hierarchical, Pyramid-Based Cancer Cell Chip for the Detection of Anticancer Drug Effects.

In this study, we developed a novel three-dimensional (3D) cancer cell chip using a three-floor hierarchical 3D pyramid structure (3D pyramid) to simulate 3D tumor cell growth in vitro and to detect anticancer drugs. The proposed 3D pyramidbased cancer cell chip offered substantial advantages for the agglomerate formation of tumor cells, in which cells could be maintained as tumor spheroids for up to 3 weeks. Soon after HeLa tumor cells adhered to the micropatterned pillar sidewalls, they were suspended between the pillars based on scanning electron microscopy images. Treatment with the anticancer drug oleanolic acid resulted in 46.33% and 5.86% apoptotic cells on the 2D plate and 3D pyramid-based cell chip, respectively, compared with only 0.06% apoptotic cells in the control. The increase in chemoresistance to anticancer drugs in the 3D pyramid-based cell chip might be a result of cell confluence and hypoxia due to the spheroid formation of tumor cells in the 3D pyramid structure. These results indicated that the proposed cell chip could potentially be used for anticancer drug screening or can be incorporated into other models aimed at prolonging various cell functions in culture.

Photosensitive functionalized surface-modified quantum dots for polymeric structures via two-photon-initiated polymerization technique.

In this paper, the surface modification of CdSe- and CdZnS-based quantum dots (QDs) with a functional silica shell is reported. Functionalized silica shells are prepared by two routes: either by ligand exchange and a modified Stöber process or by a miniemulsion process with amphiphilic poly(oxyethylene) nonylphenylether also know as Igepal CO-520 (IG) as oligomeric amphiphile and modified silica precursors. The polymerizable groups on the functionalized silica shell allow covalent bonding to a polymer matrix and prevent demixing during polymerization and crosslinking. This allows the homogeneous incorporation of QDs in a crosslinked polymer matrix. This paper furthermore demonstrates that the resulting QDs, which are i) shielded with a proper silica shell and ii) functionalized with crosslinkable groups, can be used in two-photon-initiated polymerization processes in combination with different photoresists to obtain highly luminescent 3D structures. The resulting luminescent structures are attractive candidates for photonics and metamaterials research.

Rotational elastic micro joint based on helix-augmented cross-spring design for large angular movement.

A new type of micro-joint based on an elastic design concept is proposed for large rotational movement. The proposed new 3D micro-joint was designed based on a cross-spring that has precise and reliable motion. However, the cross-spring has a limitation in the range of rotational angle. To improve the range of rotational movement, the proposed 3D micro-joint was modified with a helical structure. By adding the helical structure, the modified rotational joint can achieve large rotational movement The micro-joint was fabricated by the two-photon stereolithography process (TPS process). The micro-joint was manipulated by optical trapping force. With the same optical trapping force, the advantage of proposed cross-spring on the large rotational movement was evaluated. And the precise movement of the proposed micro-joint was evaluated by calculating the RMS error. It has been shown that the proposed 3D micro-joint has precise and reliable motion for large rotational angle.