Reflecting on Mechanical Functionalities in Bioreactors for Tissue Engineering Purposes
Corresponding email: yudan@eng.ui.ac.id
Published at : 27 Nov 2020
Volume : IJtech
Vol 11, No 5 (2020)
DOI : https://doi.org/10.14716/ijtech.v11i5.4314
Nadhif, M.H., Assyarify, H., Waafi, A.K., Whulanza, Y., 2020. Reflecting on Mechanical Functionalities in Bioreactors for Tissue Engineering Purposes. International Journal of Technology. Volume 11(5), pp. 1066-1075
| Muhammad Hanif Nadhif | 1. Department of Medical Physics, Faculty of Medicine, Universitas Indonesia, JL. Salemba Raya No.6, Jakarta 10340, Indonesia 2. Medical Technology Cluster, Indonesia Medical Education and Research I |
| Hanif Assyarify | Medical Technology Cluster, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, JL. Salemba Raya No.6, Jakarta 10340, Indonesia |
| Affan Kaysa Waafi | Department of Mechanical Engineering, Technical University of Denmark, Lyngby 2800, Denmark |
| Yudan Whulanza | 1. Department of Mechanical Engineering, Faculty of Engineering, Universitas Indonesia, Kampus UI Depok, Depok 16424, Indonesia 2. Research Center for Biomedical Engineering (RCBE), Universitas Indon |
Many articles have
reported a correlation between the use of mechanical stimulation and an
enhancement in cultivation of various tissues engineered in bioreactors. The
enhancement includes improvements in cell growth, proliferation, and
functionalities. The aim of this report is to review the mechanical
functionalities of tissue engineering bioreactors in terms of the forms of
stimulation, types of stress, actuators, supporting modules, and, most
importantly, efficacy. The Google Scholar database was searched for relevant
articles. Three forms of simulation were reported: uniaxial, biaxial, and
multiaxial. The types of stress exerted by bioreactors include compression,
tension, shear, and dynamic stresses, which are applied solely or mutually
depending on the number of axes involved. Mechanical stimulation could be
actuated by stepper motors, pistons, pneumatic pumps, diaphragm pumps,
piezoelectric systems, or dielectric charges. Additional modules, such as
incubators, flow perfusion systems, ultrasound sensors, movement controls, and
electrodes, can also support the mechanical functions of bioreactors. The
efficacy of a bioreactor could be determined by investigating the biomechanical
and histological properties of the engineered tissues. To facilitate the development
of mechanical functionalities for tissue engineering bioreactors in the future,
a seven-step framework is proposed.
Bioreactors; Mechanical functionalities; Tissue engineering
Tissue engineering has resulted in significant enhancements in medicine.
At present, engineered tissues initially developed in labs are now used in
clinics. The outcomes were a manifestation of a tissue engineering triad:
cells, scaffolds, and signals (Birla,
2014). In terms of
signals, abundant signal types and provisions, are now implemented for
engineered tissues (Birla,
2014). One of the common
provisions has been the use of bioreactors. Compared to petri dishes,
bioreactors performed superior for tissue culture
One of the bioreactors that utilized a
mechanical stimulation module was first produced in the late 1990s (Vunjak-Novakovic
et al., 1999). This group engineered cartilage constructs in rotating
vessels, which imposed a shear stress induced by a dynamic laminar flow field.
The resulting engineered cartilage constructs showed a higher fraction of
collagen and glycosaminoglycans when compared to a static culture. Moreover,
the artificial cartilage also showed better mechanical properties. After this
finding, reports flourished regarding the use of mechanical stimulations in
tissue engineering bioreactors. In most cases, mechanical stimuli were used to
induce the growth and proliferation of dermato-musculoskeletal and cardiac
muscle tissues, including skin (Helmedag
et al., 2015), heart muscles (Mooney
et al., 2012), cartilage (Vainieri
et al., 2018), bones (Rauh
et al., 2011), and skeletal muscles (Heher
et al., 2015).
As first reported by Vunjak-Novakovic et al. (1999), the outcomes of
mechanically stimulating bioreactors are often characterized by the mechanical
properties of the tissues, the cell growth and proliferation, and the presence
of extracellular matrix (ECM). The beating performance of the seeded cells are
also considerations in engineered heart muscles (Shachar et al., 2012; Paez?Mayorga et al., 2019).
Unfortunately, reviews about the
mechanical functionalities in tissue engineering bioreactors are still
scattered. The existing reports mostly focus on one type of stress or one
target tissue. For instance, a review by McCoy
and O’Brien (2010) focused on the shear stress in bone tissue
bioreactors, while a review by Anderson
and Johnstone (2017) focused more on compression stress for
engineered chondrocytes. A comprehensive review about various forms of
mechanical stimulations for broad types of tissues is still lacking, not to
mention the forms of loading and other related technical aspects.
The aim of this report was to review the
mechanical functionalities for tissue engineering bioreactors in terms of the
forms of stimulation, types of stress, actuators, supporting modules, and, most
importantly, efficacy.
The
mechanical functionalities of bioreactors can be divided into three forms of
stimulation: uniaxial, biaxial, and multiaxial. The uniaxially stimulating
bioreactors produce stresses that are compressive, tensile, shear, and
flexural. Some articles have claimed that the uniaxial stimulation they
developed could result in biaxial stress. However, that claim should be
thoroughly scrutinized since the articles lacked any experimental
characterizations. Most biaxial stimulations combined compression and shear, although
that type of stimulation could also exist as a biaxial tension. The multiaxial
system has been characterized using the bulging mechanism, actuated by a
pneumatic system acting on a dielectric elastomer. To facilitate future work in
developing mechanical functionalities of tissue engineering bioreactors, a
seven-step framework is proposed.
This research was supported by the Universitas
Indonesia Grant PIT9 in 2019 with Contract Number:
NKB-0084/UN2.R3.1/HKP.05.00/2019.
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| R3-ME-4314-20201030223039.jpg | Figure 2 |
| R3-ME-4314-20201030223058.jpg | Figure 3 |
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