Barrios, L.

Morales Paytuví, Frederic

Universitat Autònoma de Barcelona. Facultat de Biociències

Diposit Digital de Documents de la UAB

3D Stem cell bioprinters in Tissue Engineering   Organ bioprinting with three-dimensional (3D) stem cell printing technology is one of the approaches being studied nowadays in order to satisfy the organ demand of patients with a death risk who have a loss of function of some organ (caused by aging or an injury). A) B) C) D) Organ printing consist in three basic steps: •Pre-processing: Generation of a 3D model . •Processing: Construction of a Scaffold and cell deposition. •Post-processing: Maturation of the tissue construct  and transplanting. Degree in Biotechnology Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, 2014 Author: Morales Paytuví, Frederic   Tutor:    Barrios Sanromà, Lleonard 1.Introduction                          Figure 1. Non-invasive radiological images obtained from patients heart. [1][2][3]           Figure 2. 3D moldels: Computer-Aided and physical. [4] Pre-processing Post-processing Processing High-resolution images are basically taken by Multidetector computed tomography (MDCT) and Magnetic Resonance Imaging (MRI). 2. Image collection 3D model is produced by:  •Segmentation evaluation. •Surface and volume rendering. •Maximal intensity projection.  •Multiplanar reformation Thomas Boland and Cris Wilson were the first to design a cell printer by modifying a printer  firstly designed for ink printing. Nowadays Bioplotters can automatically create a 3d scaffold from CAD models. It could be done within hours while working  with a wide variety of materials.  3. Image post-processing                    Figure 3. Different Bioprinters: Mechanical structure of the first cell printer and Robotic bioprinter (3D-Bioplotter, EnvisionTEC). [5][6]       Figure 4. Schematic presentation of the different types of dropping: A) Continuous inkjet and E) Dropping-on-demand inkjet printing. [7] 4. Bioprinting Several post-processing tools are used in order to improve the quality of the images  collected and form the surfaces and volumes of the 3D object . Printers have nozzles which can be moved and placed in three-dimensional positions to accurately generate the droplets which will be implanted on the scaffold. They are ejected by pressure, heat or a piezoelectric transducer. 6. Scaffold formation Direct Cell printing Scaffold formation for cell seeding  Figure 5. Tissue spheroids technique: A) lab-scale spheroid depositer ,B) Layer-by-layer deposition of tissue spheroids to form a cylinder and C) Tissue spheroid fluorescently labelled. [8] 7. Cell seeding 9. Cerebral organoids 10. Autologous Bladders 8. Tissue Maturation Tissue spheroids are clusters of cells used for direct bioprinting. After their encapsulation in an hydrogel, they are deposited layer-by-layer and finally self-assembled.  5. Tissue Spheroids       Figure 9. Microscopic structer of scaffolds: A) Alginate, B) collagen, C) hydrogel crosslinked by Multiphoton processing techniques, D) Polymer-based scaffold. [9][10][11][12] Scaffolds serve as temporal support for the 3d cultured cells and helps in the processes of cell adhesion, growth, migration, orientation and signalling.  b c A B A B Figure 10.  Bioreactor culture:  B) Spinner flask bioreactor,   C) Irrigation dripping tripled perfusion bioreactor .  [13][14]  Different types of Stem Cells can be obtained depending on the approach. Cell seeding is enhanced by an homogenous cell distribution inside the scaffold. For an enhanced tissue formation, there is a need to have high cell densities. In addition, the diffusion of media inside the tissue is essential for the distribution of cells inside the scaffold.  Figure 11. Schematic process for  branched  production of the circulatory system. [8] Vascularization is vital for the whole organ to be correctly irrigated for the obtention of all the indispensable nutrients. Figure 12. Cerebral organoid culture labelled with neural progenitor markers.[15] Figure 13. Process to construct the engineered bladder: A) Scaffold cell-seeded and B) engineered bladder connected by anastamoses to native bladder. [16] A model of human brain was created for drug testing in matrigel spheroids in a spinning bioreactor. Moreover, it showed the crucial steps of the process such as the tissue maduration and the organ monitoring after the creation. Succesful transplants has been done with an engineered bladder with a polyglicolic acid-based scaffold.  [1]: Am J Roentgenol 2002;179:911–916. [2]: Radiat Oncol. 2013;8:295. [3]:  http://www.mricenter.com/  [4]: Int J Comput Assist Radiol Surg. 2010;5:335–341. [5]: Anat Rec Part A Discov Mol Cell Evol Biol. 2003;272:491–496 [6]:http://envisiontec.com/envisiontec-announces-launch-3d-bioplotter-developer-series-mrs-spring-meeting. [7]: Annu Rev Mater Res. 2010;40:395–414. [8]: Biomaterials. 2009;30:2164–74. [9]: RSC Adv. 2012;2:7578-7587. [10]: Polymers. 2012;2:664-680. [11]: Expert Rev Med Devices. 2012;9:613–633.  [12]: Acta Biometarialia. 2009;5:2847-2859. [13]: Trends in Biotechnology. 2004;22:80-86. [14]: Curr Opin Biotechnol. 2011;22:667-673. [15]: Nature. 2013;501:373-379 [16]: The Lancet. 2006;15:1241-1246  Conclusions References Althought 3D bioprinting is a fast-evolving technique with great potential to solve the problem of the shortage of organs donated, some limitations have appeared. More effort is needed to be done in order to increase the resolution of 3D models and improve the challenging process of vascularization. On the other hand, several objectives have been fulfilled during the past decades such as the generation of robotic bioprinters or the use of multiphoton techniques in the design of scaffolds. Future investigations will be focused on the scalability of the process and the bioprinting of  heart and kidney among others. 

3D stem cell bioprinters in tissue engineering

http://ddd.uab.cat/pub/tfg/2014/119245/TFG_fredericmoralespaytuvi.pdf

3D stem cell bioprinters in tissue engineering

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