Minghao Nie

Bio: Minghao Nie is an academic researcher from University of Tokyo. The author has contributed to research in topics: Skeletal muscle & Biofabrication. The author has an hindex of 5, co-authored 23 publications receiving 161 citations.

The bioprinting roadmap

Abstract: This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field.

Bottom-up biofabrication using microfluidic techniques.

Abstract: Nature builds living organisms in a bottom-up fashion, starting from the expression of genetic information on a cellular level, to the proliferation, differentiation, and self-assembly of cells into tissues/organs during embryo development and wound-healing processes. To mimic this bottom-up approach, it is essential to handle and manipulate small-scale biomaterials using specific technologies, such as microfluidic techniques. Microfluidics provides the tool-sets that deal with the behavior, precise control and manipulation of small amounts of fluids. Since the handling performed in aqueous environment guarantees the well-preserved bioactivities of biomaterials, microfluidic techniques show unique and critical advantages for biofabrication purposes. In this review, we report the recent progress on the bottom-up biofabrication using microfluidic techniques, such as the fabrication of microtissues, bioprinting of cell-laden tissue scaffolds, and organ-on-a-chip. As future perspectives, the deeper convergence of bottom-up approaches with top-down approaches as well as microfluidic-enabled vascularization of thick tissues is anticipated to have enormous impacts on the field of biofabrication.

Microfluidics based synthesis of coiled hydrogel microfibers with flexible shape and dimension control

Abstract: We examined a combined method to trigger liquid rope-coiling of viscous micro threads, and performed synthesis of coiled hydrogel microfibers with in-situ gelation. Using the proposed method, we achieved synthesis of microfiber based coiled hydrogel structures with flexible shape and dimension control. Coiling amplitude ranging from ca. 400 μm to ca. 2.6 mm were synthesized using a single device platform. In addition, complex shaped second-ordered coiled structures (i.e. supercoiled structures) were also synthesized.

Biofabricating murine and human myo‐substitutes for rapid volumetric muscle loss restoration

Abstract: The importance of skeletal muscle tissue is undoubted being the controller of several vital functions including respiration and all voluntary locomotion activities. However, its regenerative capability is limited and significant tissue loss often leads to a chronic pathologic condition known as volumetric muscle loss. Here, we propose a biofabrication approach to rapidly restore skeletal muscle mass, 3D histoarchitecture, and functionality. By recapitulating muscle anisotropic organization at the microscale level, we demonstrate to efficiently guide cell differentiation and myobundle formation both in vitro and in vivo. Of note, upon implantation, the biofabricated myo-substitutes support the formation of new blood vessels and neuromuscular junctions-pivotal aspects for cell survival and muscle contractile functionalities-together with an advanced muscle mass and force recovery. Altogether, these data represent a solid base for further testing the myo-substitutes in large animal size and a promising platform to be eventually translated into clinical scenarios.

3D culture of functional human iPSC-derived hepatocytes using a core-shell microfiber

Abstract: Human iPSC-derived hepatocytes hold great promise as a cell source for cell therapy and drug screening. However, the culture method for highly-quantified hepatocytes has not yet been established. Herein, we have developed an encapsulation and 3D cultivation method for iPSC-hepatocytes in core-shell hydrogel microfibers (a.k.a. cell fiber). In the fiber-shaped 3D microenvironment consisting of abundant extracellular matrix (ECM), the iPSC-hepatocytes exhibited many hepatic characteristics, including the albumin secretion, and the expression of the hepatic marker genes (ALB, HNF4α, ASGPR1, CYP2C19, and CYP3A4). Furthermore, we found that the fibers were mechanically stable and can be applicable to hepatocyte transplantation. Three days after transplantation of the microfibers into the abdominal cavity of immunodeficient mice, human albumin was detected in the peripheral blood of the transplanted mice. These results indicate that the iPSC-hepatocyte fibers are promising either as in vitro models for drug screening or as implantation grafts to treat liver failure.

Organ Printing: Tissue Spheroids as Building Blocks

Abstract: Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion - a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with "built-in" perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

Printability and Shape Fidelity of Bioinks in 3D Bioprinting.

Abstract: Three-dimensional bioprinting uses additive manufacturing techniques for the automated fabrication of hierarchically organized living constructs. The building blocks are often hydrogel-based bioinks, which need to be printed into structures with high shape fidelity to the intended computer-aided design. For optimal cell performance, relatively soft and printable inks are preferred, although these undergo significant deformation during the printing process, which may impair shape fidelity. While the concept of good or poor printability seems rather intuitive, its quantitative definition lacks consensus and depends on multiple rheological and chemical parameters of the ink. This review discusses qualitative and quantitative methodologies to evaluate printability of bioinks for extrusion- and lithography-based bioprinting. The physicochemical parameters influencing shape fidelity are discussed, together with their importance in establishing new models, predictive tools and printing methods that are deemed instrumental for the design of next-generation bioinks, and for reproducible comparison of their structural performance.

Additive manufacturing of structural materials

Abstract: Additive manufacturing (AM), also known as three-dimensional (3D) printing, has boomed over the last 30 years, and its use has accelerated during the last 5 years AM is a materials-oriented manufacturing technology, and printing resolution versus printing scalability/speed trade-off exists among various types of materials, including polymers, metals, ceramics, glasses, and composite materials Four-dimensional (4D) printing, together with versatile transformation systems, drives researchers to achieve and utilize high dimensional AM Multiple perspectives of the AM of structural materials have been raised and illustrated in this review, including multi-material AM (MMa-AM), multi-modulus AM (MMo-AM), multi-scale AM (MSc-AM), multi-system AM (MSy-AM), multi-dimensional AM (MD-AM), and multi-function AM (MF-AM) The rapid and tremendous development of AM materials and methods offers great potential for structural applications, such as in the aerospace field, the biomedical field, electronic devices, nuclear industry, flexible and wearable devices, soft sensors, actuators, and robotics, jewelry and art decorations, land transportation, underwater devices, and porous structures