International Journal

  • 2020

  • 6

    "4D‐Printed Transformable Tube Array for High‐Throughput 3D Cell Culture and Histology"

    Chen Yang, Jeffrey Luo, Marianne Polunas, Nikola Bosnjak, Sy‐Tsong Dean Chuen, Michelle Chadwick, Hatem E. Sabaawy, Shawn A. Chester, Ki‐Bum Lee*, and Howon Lee*
    Advanced Materials , 7 , 2004285 (2020)

    3D cell cultures are rapidly emerging as a promising tool to model various human physiologies and pathologies by closely recapitulating key characteristics and functions of in vivo microenvironment. While high-throughput 3D culture is readily available using multi-well plates, assessing the internal microstructure of 3D cell cultures still remains extremely slow because of the manual, laborious, and time-consuming histological procedures. Here, a 4D-printed transformable tube array (TTA) using a shape-memory polymer that enables massively parallel histological analysis of 3D cultures is presented. The interconnected TTA can be programmed to be expanded by 3.6 times of its printed dimension to match the size of a multi-well plate, with the ability to restore its original dimension for transferring all cultures to a histology cassette in order. Being compatible with microtome sectioning, the TTA allows for parallel histology processing for the entire samples cultured in a multi-well plate. The test result with human neural progenitor cell spheroids suggests a remarkable reduction in histology processing time by an order of magnitude. High-throughput analysis of 3D cultures enabled by this TTA has great potential to further accelerate innovations in various 3D culture applications such as high-throughput/content screening, drug discovery, disease modeling, and personalized medicine. 
  • 5

    "Rapid Processing and Drug Evaluation in Glioblastoma Patient-Derived Organoid Models with 4D Bioprinted Arrays"

    Michelle Chadwick†, ChenYang† († equal contribution), Liqiong Liu, Christian Moya Gamboa, Kelly Jara, Howon Lee*, and Hatem E.Sabaawy*
    iScience , 23(8) , 101365 (2020)

     Glioblastoma is the most common and deadly primary brain malignancy. Despite advances in precision medicine oncology (PMO) allowing the identification of molecular vulnerabilities in glioblastoma, treatment options remain limited, and molecular assays guided by genomic and expression profiling to inform patient enrollment in life-saving trials are lacking. Here, we generate four-dimensional (4D) cell-culture arrays for rapid assessment of drug responses in glioblastoma patient-derived models. The arrays are 3D printed with thermo-responsive shape memory polymer (SMP). Upon heating, the SMP arrays self-transform in time from 3D cell-culture inserts into histological cassettes. We assess the utility of these arrays with glioblastoma cells, gliospheres, and patient derived organoid-like (PDO) models and demonstrate their use with glioblastoma PDOs for assessing drug sensitivity, on-target activity, and synergy in drug combinations. When including genomic and drug testing assays, this platform is poised to offer rapid functional drug assessments for future selection of therapies in PMO.
  • 4

    "Recent Advances in Multi-Material Additive Manufacturing: Methods and Applications"

    Daehoon Han and Howon Lee*
    Current Opinion in Chemical Engineering , 28 , 158-166 (2020)

     Multi-material additive manufacturing (MMAM) enables rapid design and direct fabrication of three-dimensional (3D) objects consisting of multiple materials without the need for complex manufacturing process and expensive tooling. Through concurrent integration of multiple materials having their own unique properties, MMAM allows for facile production of multi-functional devices and systems. Various MMAM techniques have recently been developed and a wide range of new applications have been demonstrated using MMAM. This paper reviews recent advances in MMAM methods and key applications enabled by MMAM in three areas; biomedical engineering, soft robotics, and electronics.
  • 3

    "Self-Limiting Electrospray Deposition for the Surface Modification of Additively Manufactured Parts"

    Dylan Kovacevich†, Lin Lei† († equal contribution), Daehoon Han, Christianna Kuznetsova, Steven E. Kooi, Howon Lee, and Jonathan P. Singer*
    ACS Applied Materials & Interfaces , 12(18) , 20901 (2020)

    Electrospray deposition (ESD) is a spray coating process that utilizes a high voltage to atomize a flowing solution into charged microdroplets. These self-repulsive droplets evaporate as they travel to a target substrate, depositing the solution solids. Our previous research investigated the conditions necessary to minimize charge dissipation and deposit a thickness-limited film that grows in area over time through self-limiting electrospray deposition. Such sprays possess the ability to conformally coat complex three-dimensional (3D) objects without changing the location of the spray needle or orientation of the object. This makes them ideally suited for the postprocessing of materials fabricated through additive manufacturing (AM), opening a paradigm of independent bulk and surface functionality. Having demonstrated 3D coating with film thickness in the range of 1–50 μm on a variety of conductive objects, in this study, we employed model substrates to quantitatively study the technique’s limits with regard to geometry and scale. Specifically, we examined the effectiveness of thickness-limited ESD for coating recessed features with gaps ranging from 50 μm to 1 cm, as well as the ability to coat surfaces hidden from the line-of-sight of the spray needle. This was then extended to the coating of hydrogel structures printed by AM, demonstrating that coating could be conducted even into the body of the structures as a means to create hydrophobic surfaces without affecting the absorption-driven humidity response. Further, these coatings were robust enough to create superhydrophobicity in the entire structure, causing it to resist immersion in water. 
  • 2

    "Immobilization of Laccase on a Graphene Interface: Direct Electron Transfer and Molecular Dynamics Study"

    Taeyoung Yoon, Inchul Baek, Seonwoo Lee, Hyunsung Choi, Seongho Yoon, Howon Lee, Sunwoong Kim, and Sungso Na
    Applied Surface Science , 521 , 146378 (2020)

     Direct electron transfer (DET) in biocatalysts and the interactions of biocatalysts at electrode interfaces are critical issues for the development of electrochemical devices. In comparison to high-performance complex electrodes, graphene-based electrodes have attracted significant attention based on their superior electrical conductivity, material properties, and low cost. However, the immobilization of laccase (LAC), an oxygen-reducing enzyme with high catalytic activity that is applied to cathodes, and interfaces formed between LAC and graphene have rarely been explored. In this study, electrochemical experiments employing cyclic voltammetry and electrochemical impedance spectroscopy were performed, and it was determined that graphene exhibits a maximum of a 1.57-fold increase in terms of its oxygen reduction rate compared to Au and carbon nanotubes. Additionally, DET rate revealed that graphene behaves more efficiently on immobilized LAC. Furthermore, absorbed morphologies were visualized, and computational methods were applied to verify binding sites, orientations, structures, and binding affinities in atomic scale. The axial ligands at T1 Cu sites were mutated using different hydrophobic amino acids, and the effects of mutation on interactions at interfaces were compared. Based on our experimental and theoretical results, LAC immobilization on graphene appears to be stronger than that on a charged surface without critical structural changes.
  • 1

    "4D Printing of a Bioinspired Microneedle Array with Backward-Facing Barbs for Enhanced Tissue Adhesiona"

    Daehoon Han†, Riddish S. Morde†, Stefano Mariani† († equal contribution), Antonino A. La Mattina, Emanuele Vignali, Chen Yang, Giuseppe Barillaro*, and Howon Lee*
    Advanced Functional Materials , 3 , 1909197 (2020)

     Microneedle (MN), a miniaturized needle with a length-scale of hundreds of micrometers, has received a great deal of attention because of its minimally invasive, pain-free, and easy-to-use nature. However, a major challenge for controlled long-term drug delivery or biosensing using MN is its low tissue adhesion. Although microscopic structures with high tissue adhesion are found from living creatures in nature (e.g., microhooks of parasites, barbed stingers of honeybees, quills of porcupines), creating MNs with such complex microscopic features is still challenging with traditional fabrication methods. Here, a MN with bioinspired backward-facing curved barbs for enhanced tissue adhesion, manufactured by a digital light processing 3D printing technique, is presented. Backward-facing barbs on a MN are created by desolvation-induced deformation utilizing cross-linking density gradient in a photocurable polymer. Barb thickness and bending curvature are controlled by printing parameters and material composition. It is demonstrated that tissue adhesion of a backward-facing barbed MN is 18 times stronger than that of barbless MN. Also demonstrated is sustained drug release with barbed MNs in tissue. Improved tissue adhesion of the bioinspired MN allows for more stable and robust performance for drug delivery, biofluid collection, and biosensing.
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