Bioreactors for Advanced Cell Culture, (Nano)toxicity, Regenerative Medicine and Organ Bioengineering, Volume II

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 1632

Special Issue Editor


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Guest Editor
Department of Information Engineering and Research Center ‘E. Piaggio’, University of Pisa, 56126 Pisa, PI, Italy
Interests: advanced in-vitro models; viscoelasticity; biomaterials; biofabrication; mechanotrandsuction
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Special Issue Information

Dear Colleagues,

From the micro- to the macroscale, bioreactors are widely used for advanced cell culture. They can be used as tools for regenerative medicine and for generating physiologically relevant in vitro models. Thus, they can be used as animal model alternatives in drug testing, toxicology applications and, more in general, to investigate the interaction of different substances, nanomaterials and pathogens with the human body and immune cells. For these applications, biological interfaces such as lung, intestine, skin and blood vessels, as well as vital organs (liver, heart, brain and kidney) and structural/functional tissues (bone, cartilage, muscles), are of particular interest.

Combining engineering and biology, bioreactors are able to replicate key features of organ and tissues and to provide the cells with dynamic stimuli such as flow or mechanical and electrical cues. Current challenges relate to the integration of sensing for real-time monitoring of cell conditions and with the definition of novel actuation strategies to imitate physiological deformation mechanism. Other fundamental innovations regard the combination of bioreactor and biomaterials to mimic tissue and organ 3D architectures and mechanical properties, which are typically time-dependent (viscoelastic) and may evolve during time according to pathophysiological processes.

From this perspective, this Special Issue on ‘Bioreactors for Advanced Cell Culture, (Nano)toxicity, Regenerative Medicine and Organ Bioengineering’ will collect innovative research articles and targeted reviews which deal with novel and bold applications and with new solutions for improving bioreactor technology. For instance, applications may be related to different areas of regenerative medicine and to nanomaterial toxicology from a molecular and mechanistic perspective. Innovative solutions may include the use of non- (or low-)invasive actuation and sensing strategies based on smart materials or systems or the integration of in silico strategies able to improve the relevance of the experimental conditions or result translation.

Dr. Ludovica Cacopardo
Guest Editor

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Keywords

  • bioreactors
  • advanced cell culture
  • tissue and organ engineering
  • biomaterials
  • smart materials
  • actuation
  • sensing
  • 3D tissue architecture
  • time-dependent and time-evolving mechanical properties
  • in vitro/in silico approach
  • regenerative medicine
  • in vitro models
  • nanomaterials
  • toxicology
  • animal model alternatives
  • in vitro toxicity
  • hazard assessment
  • nanomedicine

Published Papers (1 paper)

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Research

26 pages, 5979 KiB  
Article
Perfusion of MC3T3E1 Preosteoblast Spheroids within Polysaccharide-Based Hydrogel Scaffolds: An Experimental and Numerical Study at the Bioreactor Scale
by Jérôme Grenier, Bertrand David, Clément Journé, Iwona Cicha, Didier Letourneur and Hervé Duval
Bioengineering 2023, 10(7), 849; https://doi.org/10.3390/bioengineering10070849 - 18 Jul 2023
Cited by 3 | Viewed by 1251
Abstract
The traditional 3D culture systems in vitro lack the biological and mechanical spatiotemporal stimuli characteristic to native tissue development. In our study, we combined porous polysaccharide-based hydrogel scaffolds with a bioreactor-type perfusion device that generates favorable mechanical stresses while enhancing nutrient transfers. MC3T3E1 [...] Read more.
The traditional 3D culture systems in vitro lack the biological and mechanical spatiotemporal stimuli characteristic to native tissue development. In our study, we combined porous polysaccharide-based hydrogel scaffolds with a bioreactor-type perfusion device that generates favorable mechanical stresses while enhancing nutrient transfers. MC3T3E1 mouse osteoblasts were seeded in the scaffolds and cultivated for 3 weeks under dynamic conditions at a perfusion rate of 10 mL min−1. The spatial distribution of the cells labeled with superparamagnetic iron oxide nanoparticles was visualized by MRI. Confocal microscopy was used to assess cell numbers, their distribution inside the scaffolds, cell viability, and proliferation. The oxygen diffusion coefficient in the hydrogel was measured experimentally. Numerical simulations of the flow and oxygen transport within the bioreactor were performed using a lattice Boltzmann method with a two-relaxation time scheme. Last, the influence of cell density and spheroid size on cell oxygenation was investigated. The cells spontaneously organized into spheroids with a diameter of 30–100 μm. Cell viability remained unchanged under dynamic conditions but decreased under static culture. The cell proliferation (Ki67 expression) in spheroids was not observed. The flow simulation showed that the local fluid velocity reached 27 mm s−1 at the height where the cross-sectional area of the flow was the smallest. The shear stress exerted by the fluid on the scaffolds may locally rise to 100 mPa, compared with the average value of 25 mPa. The oxygen diffusion coefficient in the hydrogel was 1.6×109 m2 s−1. The simulation of oxygen transport and consumption confirmed that the cells in spheroids did not suffer from hypoxia when the bioreactor was perfused at 10 mL min−1, and suggested the existence of optimal spheroid size and spacing for appropriate oxygenation. Collectively, these findings enabled us to define the optimal conditions inside the bioreactor for an efficient in vitro cell organization and survival in spheroids, which are paramount to future applications with organoids. Full article
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