3D HYBRID ORGAN-ON-CHIP (HOCP) PLATFORM FOR SKELETAL MUSCLE TISSUE: A PREDICTIVE IN VITRO MODEL AND AN ADVANCED TOOL FOR IN VIVO REPAIR OF SKELETAL MUSCLE DEFECTS
Starting date: 1 May 2019
Is it possible to fabricate in vitro artificial, functional tissues and organs?
Tissues and organs are complex hierarchical structures composed of multiple cell types and
site-specific extra-cellular matrix. Reproducing in vitro the specific functions of organs and tissues,
such as the regular beating of heart, the detoxification abilities of liver, the contraction of muscles
etc. within an artificial engineered constructs is extremely challenging.
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Nowadays, the development of alternative functional in vitro models of organs and tissues is
becoming a real necessity. The reasons of that are numerous. Firstly, the costs of new drug research
and development are constantly growing. As a consequence, pharmaceutical companies are searching
for more accurate and cost saving methods to screen pre-clinically their potential pipelines to reduce
the risk of wasting potentially valuable drugs. Secondly, relying on animal research and testing to
improve human health is not only expensive, but also unsafe, time-consuming, not always reliable
and often considered cruel by the public opinion. Problems of extrapolation (i.e. applying information
from animal research to humans) are inevitable when researchers use animal models to study human
diseases. Species differences in anatomy, organ structure and function, toxin metabolism, chemical
and drug absorption, and mechanisms of DNA repair — among myriad other differences between
humans and other species — can give us inadequate or erroneous information when we attempt to
apply animal data to human diseases and drug responses.
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In this context, we propose to develop an innovative hybrid organ-on-chip (hOCP) platform
for the creation of a functional human model of skeletal muscle tissue. An organ-on-a-chip is a
microfluidic cell culture device that contains continuously perfused and/or actuated (generally
vacuum-actuated) micro-chambers/channels inhabited by living cells arranged to simulate tissue- and
organ-level physiology. By recapitulating the multicellular architectures, tissue-tissue interfaces,
physicochemical microenvironments and vascular perfusion of the body, these devices produce levels
of tissue and organ functionality not possible with conventional 2D or 3D culture systems.
Based on our experience, we will precisely confine in 3D myogenic adult stem cells, endothelial
cells and fibroblasts within a biodegradable hydrogel to mimic the native cellular organization.
Furthermore, to support the neo-tissue development, cells will be cultured in a controlled microenvironment in which specific mechanical, electrical and chemical stimuli will be provided.
The proposed system might find applications both in vitro as a predictive model for drug
discovery and testing, for toxicity studies and to investigate disease etiology, and in vivo for the repair
of skeletal muscle defects that can arise after traumas, surgeries or degenerative diseases.
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This project is carried out under POLONEZ programme managed by the National Science Centre—Poland (NCN, fellowship number 2016/23/P/NZ1/03604) which has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 665778.
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ENGINEERING MICROVASCULATURE VIA 3D BIOPRINTING WITH INNOVATIVE BIOINK ADDITIVES
Starting date: 1 November 2019
The development of artificial organs may represent a life-saving solution for all those people waiting for an organ transplant. Large part of the research conducted worldwide on this topic is focusing the attention on mimicking native cell organization and matrix composition as close as possible so as to promote tissue/organ specific functions. In particular, great efforts are being spent to integrate capillary networks – i.e. microvasculature – inside engineered tissue constructs. The integration of artificial microvascular networks to transport nutrients and oxygen and remove wastes is critical not only for developing engineered tissues for clinical applications but also for maintaining vital functions of cells within in vitro systems. Vascular networks are, in fact, particularly important for engineering physiological systems of highly metabolic organs, such as muscles, liver, and kidney. In addition, studying angiogenesis – i.e. the formation of new blood vessels form from pre-existing ones – is critical for understanding various physiological processes, including wound healing and tumor growth. In this context, we propose to develop a new approach to guide endothelial cell (i.e. the cells specialized in the formation of blood vessels) organization into a capillary network. This is planned to be achieved through the fabrication of ‘microvasculature seeds’ that, after maturation, will eventually form a microvasculature network within the engineered constructs. The project will be implemented using state-of-the-art technologies such as microfluidics and 3D bioprinting. Throughout the project, we will study in details the biochemical and biomechanical processes that orchestrate the formation of the microvasculature, with the aim of unravelling new key aspects and factors involved with this complex process. We believe that the outcome of the proposed project, if successful, may truly boost the development of advanced models of organs and tissues, with potential high economic and social repercussions in the shortto-middle term.
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