• International Journal of Technology (IJTech)
  • Vol 11, No 5 (2020)

Reflecting on Mechanical Functionalities in Bioreactors for Tissue Engineering Purposes

Reflecting on Mechanical Functionalities in Bioreactors for Tissue Engineering Purposes

Title: Reflecting on Mechanical Functionalities in Bioreactors for Tissue Engineering Purposes
Muhammad Hanif Nadhif, Hanif Assyarify, Affan Kaysa Waafi, Yudan Whulanza

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Cite this article as:
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

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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
Email to Corresponding Author

Abstract
Reflecting on Mechanical Functionalities in Bioreactors for Tissue Engineering Purposes

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

Introduction

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 functions, as they allowed for dynamic (Nadhif et al., 2017) and three-dimensional culture of tissues (Heher et al., 2015), as well as providing the possibility of mechanical stimulation (Anderson and Johnstone, 2017). Mechanical stimulations are important for in vitro tissue engineering as they model the mechanical perturbations received by the tissues in vivo. The absence of mechanical stimulation in vitro may result in deviations in mechanical properties of the final cultured tissues, thereby causing deviations in the expected tissue models.

        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. 


Conclusion

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.

Acknowledgement

This research was supported by the Universitas Indonesia Grant PIT9 in 2019 with Contract Number: NKB-0084/UN2.R3.1/HKP.05.00/2019.

Supplementary Material
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R3-ME-4314-20201030223025.jpg Figure 1
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