Focused Session FA-5 / FQ-8
3D Bioprinting of Soft Tissues and Organs


FA-5/FQ-8:IL02  Biofabrication: From Additive Manufacturing to Bioprinting and Bioassembly for Regenerative Medicine Applications
L. Moroni, A. ALDANA, Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Complex Tissue Regeneration Department, Maastricht, The Netherlands

Organs are complex systems, comprised of different tissues, proteins, and cells, which communicate to orchestrate a myriad of functions in our bodies. Technologies are needed to replicate these structures towards the development of new therapies for tissue and organ repair, as well as for in vitro 3D models to better understand the morphogenetic biological processes that drive organogenesis. To construct tissues and organs, biofabrication strategies are being developed to impart spatiotemporal control over cell-cell and cell-extracellular matrix communication, often through control over cell and material deposition and placement. Here, we present some of our most recent advancements in biofabrication that enabled the control of cell activity, moving towards enhanced tissue regeneration as well as the possibility to create more complex 3D in vitro models to study biological processes.

FA-5/FQ-8:IL03  Putting 3D Bioprinting to the Use of Tissue Model Fabrication
Y. Shrike Zhang, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, USA

The talk will discuss our recent efforts on developing a series of bioprinting strategies including sacrificial bioprinting, microfluidic bioprinting, and multi-material bioprinting, along with various cytocompatible bioink formulations, for the fabrication of biomimetic 3D tissue models. These platform technologies, when combined with microfluidic bioreactors and bioanalysis, will likely provide new opportunities in constructing functional microtissues with a potential of achieving precision therapy by overcoming certain limitations associated with conventional models based on planar cell cultures and animals.

FA-5/FQ-8:IL06  Biofabricating Murine and Human Myo-substitutes for Rapid Volumetric Muscle Loss Restoration
M. Costantini, Institute of Physical Chemistry - PAS, Warsaw, Poland; C. Gargioli, Università degli studi di Roma - Tor Vergata, Rome, Italy

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 along with muscle mass and force recovery. Together, 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.

FA-5/FQ-8:L07  Nano-encapsulation of Stem Cell-derived b-cell Aggregates using 3D Bioprinting System
Yeonggwon JO, D.G. Hwang, M. Kim, S. Cho, J. Jang, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, South Korea

Though pancreatic islet transplantation is regarded as a promising treatment for type 1 diabetes, the clinical trial is still challenging due to immune rejection and donor shortage problem. To protect islets from immune response, various encapsulation strategies have been investigated. The encapsulation system is able to provide a suitable environment for islets to survive and function without life-long immune suppression. The semi-permeable encapsulation system selectively allow the nutrients and oxygen to pass while excluding immune molecules. Furthermore, differentiating stem cells into β-cell have a chance to be supplied as the donated organs. The in vitro cultured β-cells can be fabricated into engineered pancreas and its function can be enhanced by providing a tissue-specific microenvironment. In this study, we fabricated the stem cell-derived β-cell into islet-like aggregates beside the bioprinted vasculature and cultured inside the nano-encapsulation system. The intercellular interaction of β-cell aggregates and the vascularization were induced by using 3D bioprinting system.

FA-5/FQ-8:L08  Modular Assembly of 3D Bioprinted Engineered Heart Tissue to Reconstruct Contractile Direction to Mimic Myocardial Fiber Orientation
DONG GYU HWANG, U. Yong, H. Choi, J. Jang, POSTECH, Pohang, Gyeongbuk, South Korea

An engineered heart tissue (EHT) derived from human induced pluripotent stem cells (hiPSCs) allows studying human cardiac pathophysiology. Various types of EHT such as spheroid, strip, and ring have been reported to exhibit contractility and electrophysiological properties of the native heart. However, the limited geometric complexity of these models remains a challenge to achieve other cardiac functions including volume-pressure handling and pump fluid. In this study, we propose a strategy to achieve the myocardial fiber orientation using 3D bioprinting-based modular tissue engineering. The myocardial fiber orientation, which is associated with efficient systolic function, is a unique structural feature of the heart. We employed 3D bioprinting for rapid prototyping of EHT modules in various shapes and sizes. The developed EHT module was confirmed to reproduce cardiac-specific functions such as contractility, electrophysiological properties, and drug responsiveness. Furthermore, the EHT modules were assembled to reconstruct contractile direction to mimic native myocardial fiber orientation. These findings will be applied to fabricate a chamber-like construct that contains myocardial fiber orientation.

FA-5/FQ-8:IL09  Strategies for Bioprinting of Volumetric Tissue Constructs
M. GelinskY, Centre for Translational Bone, Joint and Soft Tissue Research, TU Dresden, Dresden, Germany

Bioprinting (BP) is making enormous progress in the moment and novel technologies, materials and applications are presented. For clinical use one limitation still is the possibility to manufacture volumetric constructs of relevant size as materials which are suitable for printing of live cells often do not allow fabrication of well-defined and mechanically stable structures. Especially for musculoskeletal tissues like bone and cartilage, constructs with sufficient stability are required for clinical application. We have developed a number of bioinks, consisting of biopolymer blends and composites which provide a better shape fidelity than conventional hydrogels, often used for extrusion BP. The biological properties of the respective bioinks could be improved by adding human blood plasma. In addition, we succeeded in utilising a self-setting calcium phosphate bone cement as support material for BP of bone-like tissue constructs as the stiff mineral framework provides mechanical strength. This material combination also allows fabrication of volumetric samples with open and interconnected macropores which support oxygen and nutrient diffusion throughout the construct. Finally, the use of core/shell bioprinting enables easy integration of growth factors for local delivery.

FA-5/FQ-8:IL10  Organ-on-chip Technology for the Study of Neuro-degenerative Disorders
A. POLINI, CNR Nanotec, Lecce, Italy

Understanding the complex communication between different cell populations and their interaction with the microenvironment in the central and peripheral nervous systems is fundamental in neuroscience research. Due to the lack of suitable animal models capable of faithfully reproducing the physio-pathological mechanisms of many human diseases, the development of appropriate in vitro approaches and tools, able to selectively analyze and probe specific cells and cell portions (e.g., axons and cell bodies in neurons) has become therefore crucial in this direction. Here, an overview on the potential of Organ-on-chip technology in this field will be introduced, highlighting how we can recapitulate key functions of different organ portions by integrating relevant cell types, physical forces, (bio-) chemical concentration and gradients with unprecedented confidence, and spatio-temporally recreating physical, biological and chemical features of the target microenvironment.

FA-5/FQ-8:IL11  3D in Vitro Model of the Microbiota-gut-bone Axys
G. VOZZI, F. Biagini, F. Montemurro, C. De Maria, Research Center “E. Piaggio” and Department of Information Engineering, University of Pisa, Pisa, Italy; M. Calvigioni, E. Ghelardi, Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; G. Cerqueni, S. Marchi, M. Mattioli-Belmonte, DISCLIMO, Università Politecnica delle Marche, Ancona Italy

Despite knowledge the human gut microbiota regulates bone mass, mechanisms governing the normal gut microbiota’s osteo-immunomodulatory effects on skeletal homeostasis and remodelling are still unclear. In this context, the present work aimed at recreating a 3D in vitro model of the human gut microbiota and bone tissue crosstalk using Caco2 and Saos2 cell line for the gut and bone tissue respectively. The human gut microbiota from a healthy donor was cultured on electrospun gelatine structures to support the growth and the formation of a stable biofilm. Then, for the preliminary test, supernatant was dialyzed and used in the cell culture showing that the dialyzed supernatant doesn’t interfere with the viability of the cells respect to a non-dialyzed one. Our preliminary data demonstrate the validity of our system for in vitro modelling the crosstalk between the human gut microbiota and bone tissue. Other results will be presented at the conference.

FA-5/FQ-8:L12  A Biohybrid 3D-printed Tissue-sensor Platform for Continuous Monitoring of Cardiac Muscle Contractions
UIJUNG YONG1, D. Kim1, H. Kim2, D. G. Hwang1, S. Cho1, H. Nam1, S. Kim1, T. Y. Kim1, U. Jeong1, K. Kim1, W. K. Chung1, W.H. Yeo2, J. Jang1, 1POSTECH, Pohang, Gyeongsangbuk-do, South Korea; 2Georgia Institute of Technology, Atlanta, GA, USA

Engineered heart tissue (EHT), made up of cardiac cells and a hydrogel, has long been thought to be a viable in vitro cardiac model since it can mimic the physiological contractions of an animal heart. The contractile force of EHT, in particular, is one of the typical criteria for evaluating drug-induced cardiotoxicity, which is a key reason of drug development withdrawal. Although there have been numerous methods for monitoring the EHT's contractile force, the majority of them rely on optical readout systems that must handle a large amount of image data. In recent years, a strain gauge-based microphysiological device for monitoring the contractile force of laminar heart tissue was created, and it can capture real-time data with a tiny amount of data. However, the device can only monitor few layers of cardiomyocytes, which is a physiologically less relevant compared to EHT. In this study, we created a biohybrid 3D printed tissue-sensor platform with six bi-pillar-grafted strain gauges (BPSGs) and one wireless device that allows for real-time online monitoring of contractile forces from six separate EHTs during culturing. We also confirmed that our approach is capable of detecting the impact of commercially available medications on EHTs.

FA-5/FQ-8:L13  3D Bioprinting of Human Islet-like Cellular Aggregates-Vascular Platform for Modeling Diabetes
MYUNGJI KIM, S. Cho, D.G. Hwang, J. Jang, POSTECH, Pohang, Gyeongbuk, South Korea

Pancreatic islets have spheroidal microarchitecture, surrounded by vasculatures and extracellular matrix (ECM), and are located along with blood vessels. However, current stem cell (SC)-based islet models lack the pancreatic tissue-specific microenvironment and vascular features of islets. In this regard, we developed pancreatic tissue-derived ECM-based peri-islet niche-like (PINE) bioink supplemented with basement membrane proteins, which can promote the structural integrity of islets and the functional maturation of β cells by providing biochemical cues. We further investigated whether the co-culture of endothelial cells could enhance insulin secretion capacity of SC-derived islets via secreting paracrine factors. Finally, we fabricated human islet-like cellular aggregates-vascular platform using PINE bioink and 3D bioprinting technology to recapitulate each unique tissue architecture (e.g., spheroid and tubular structure) and validated the applicability of this platform for diabetes modeling. The developed platform reflected not only structural characteristics of pancreatic tissue and but also physiomimetic responses of diabetic islets and vessels. Our platform will facilitate developing improved pharmacotherapies for patients, opening chances for precision diabetic medicine.

FA-5/FQ-8:IL15  Implantable Bioprinted Devices for Vascularisation Studies
B. DERBY, Department of Materials, University of Manchester, Manchester, UK

The ability to promote vascularisation remains a key target for the selection of appropriate printable biomaterials for implantable devices, targeted for issue and organ regeneration. Here we present the use of an implantable bioprinted device, developed for in vivo animal studies using rat or mouse models. This can be used as a model structure for vascularistion studies using either a arterioevenous (AV) loop or an embedded microvessel within an animal model. These devices allow the screening of candidate biomaterials, the assessment of channel patterns and the influence of composition gradients in printed vascular models. Results are presented from an in vivo study of vascularisation, comparing a range of potential ECM mimicking biomaterials and decellularized tissue based hydrogels against a standard photocrosslinked Gelatin Methacroyl matrix with a simple single branching node vascular structure produced by printing a sacrificial Pluronic F127 thermoreversible hydrogel.

FA-5/FQ-8:IL17  Toward in vitro Tissue Modeling using Bioprinting Technology
JINAH JANG, POSTECH, Pohang, Gyeongbuk, South Korea

A significant transition of 3D bioprinting technology into the biomedical field helps to improve the function of engineered tissues by recapitulating physiologically relevant geometry, complexity, and vascular network. Bioinks, used as printable biomaterials, facilitate dispensing of cells through a dispenser as well as support their viability and function by providing engineered extracellular matrix. The successful construction of functional human tissues requires accurate environments that are able to mimic the biochemical and biophysical properties of the target tissue. This talk will cover my research interests in building 3D human tissues and organs to understand, diagnose, and treat various intractable diseases, including cardiovascular, diabetic diseases and cancers. Combined with recent advances in human pluripotent stem cell technologies, printed human tissues could serve as an enabling platform for studying complex physiology in tissue and organ contexts of individuals.


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