Application of Bioreactors to Improve Functionality of Bone Tissue Engineering Constructs: A Systematic Review

Nokhbatolfoghahaei, Hanieh; Rad, Maryam Rezai; Khani, Mohammad‐Mehdi; Shahriari, Shayan; Nadjmi, Nasser; Khojasteh, Arash

doi:10.2174/1574888x12666170822100105

Cited by 17 publications

(11 citation statements)

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“…The dynamic nature of the body and bone tissue has led bone tissue engineering toward the utilization of device including bioreactor system, simulating body’s physiological and mechanical environments. 1–3 Bioreactors have been shown to enhance osteogenic capability of bioscaffolds. 4–7 Besides, they can develop a structure similar to bone tissue having extra cellular matrix termed as “in vitro bone tissue morphogenesis.” 4,8,9 Moreover, translation of bone tissue engineering to clinical practices has highlighted the demand for construction of large implants for critical-sized bone defects.…”

Section: Introductionmentioning

confidence: 99%

“…10–13 However, application of large grafts is mainly restricted due to limited penetration of cells into the structures, and inhomogeneous nutrient transport, which both reduce cell survival and proliferation within the core regions of the graft. 1,9,14–16 Bioreactor systems can facilitate the construction of functional bone grafts by reinforcing media convection around seeded cells and induction of flow-generated shear stimulation. 15,17 However, influence of multiple factors such as fluid flow rate, pattern of nutrient distribution and amount of flow-induced shear stress inside bioreactors can strongly affect their outcome.…”

Section: Introductionmentioning

confidence: 99%

“…19,20,27 However, shear stress is affected by all of previous mentioned parameters; hence, it is the most important and the only comparable factor. 1,2,3,15,18…”

Section: Introductionmentioning

confidence: 99%

“…Perfusion bioreactors have been reported as the most efficient types of shear-loading bioreactor for bone tissue engineering. 1,28 Also, it has been noticed that bioreactors with a combination of forces, such as rotation plus perfusion, were considerably in favor of cell growth and osteogenic differentiation. 1…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Computational modeling of media flow through perfusion-based bioreactors for bone tissue engineering

Nokhbatolfoghahaei

Bohlouli

Adavi

et al. 2020

Proc Inst Mech Eng H

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Bioreactor system has been used in bone tissue engineering in order to simulate dynamic nature of bone tissue environments. Perfusion bioreactors have been reported as the most efficient types of shear-loading bioreactor. Also, combination of forces, such as rotation plus perfusion, has been reported to enhance cell growth and osteogenic differentiation. Mathematical modeling using sophisticated infrastructure processes could be helpful and streamline the development of functional grafts by estimating and defining an effective range of bioreactor settings for better augmentation of tissue engineering. This study is aimed to conduct computational modeling for newly designed bioreactors in order to alleviate the time and material consuming for evaluating bioreactor parameters and effect of fluid flow hydrodynamics (various amounts of shear stress) on osteogenesis. Also, biological assessments were performed in order to validate similar parameters under implementing the perfusion or rotating and perfusion fluid motions in bioreactors’ prototype. Finite element method was used to investigate the effect of hydrodynamic of fluid flow inside the bioreactors. The equations used in the simulation to calculate the velocity values and consequently the shear stress values include Navier–Stokes and Brinkman equations. It has been shown that rotational fluid motion in rotating and perfusion bioreactor produces more velocity and shear stress compared with perfusion bioreactor. Moreover, implementing the perfusion together with rotational force in rotating and perfusion bioreactors has been shown to have more cell proliferation and higher activity of alkaline phosphatase enzyme as well as formation of extra cellular matrix sheet, as an indicator of bone-like tissue formation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…19,20,27 However, shear stress is affected by all of previous mentioned parameters; hence, it is the most important and the only comparable factor. 1,2,3,15,18…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Computational modeling of media flow through perfusion-based bioreactors for bone tissue engineering

Nokhbatolfoghahaei

Bohlouli

Adavi

et al. 2020

Proc Inst Mech Eng H

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“…The manufacturing of cells based on advanced therapy medicinal products (ATMP) requires technologies that address both scaling and bioprocess challenges . Bioreactors have been adopted as an enabling technology for ATMP production both for a single cell as well as tissue culture . In contrast to static 2D culture in flasks or cell factories, bioreactors can incorporate sensors, allowing the identification and control of critical culture parameters such as temperature, pH, dissolved oxygen (DO), or the fluidic pattern (i.e., perfusion, mixing, or agitation).…”

Section: Introductionmentioning

confidence: 99%

Towards Self‐Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture

Bournonville

Lambrechts

Vanhulst

et al. 2019

Biotechnology Journal

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Bioreactors are crucial tools for the manufacturing of living cell‐based tissue engineered products. However, to reach the market successfully, higher degrees of automation, as well as a decreased footprint still need to be reached. In this study, the use of a benchtop bioreactor for in vitro perfusion culture of scaffold‐based tissue engineering constructs is assessed. A low‐footprint benchtop bioreactor system is designed, comprising a single‐use fluidic components and a bioreactor housing. The bioreactor is operated using an in‐house developed program and the culture environment is monitored by specifically designed sensor ports. A gas‐exchange module is incorporated allowing for heat and mass transfers. Titanium‐based scaffolds are seeded with human periosteum‐derived cells and cultured up to 3 weeks. The benchtop bioreactor constructs are compared to benchmark perfusion systems. Live/Dead stainings, DNA quantifications, glucose consumption, and lactate production assays confirm that the constructs cultured in the benchtop bioreactor grew similarly to the benchmark systems. Manual regulation of the system set points enabled efficient alteration of the culture environment in terms of temperature, pH, and dissolved oxygen. This study provides the necessary basis for the development of low‐footprint, automated, benchtop perfusion bioreactors and enables the implementation of active environment control.

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Bioreactor cultivation condition for engineered bone tissue: Effect of various bioreactor designs on extra cellular matrix synthesis

Nokhbatolfoghahaei

Bohlouli

Paknejad

et al. 2020

J Biomedical Materials Res

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Dynamic-based systems are bio-designed in order to mimic the micro-environments of the bone tissue. There is limited direct comparison between perfusion and perfusion-rotation forces in designing a bioreactor. Hence, in current study, we aimed to compare given bioreactors for bone regeneration. Two types of bioreactors including rotating & perfusion and perfusion bioreactors were designed. Mesenchymal stem cells derived from buccal fat pad were loaded on a gelatin/ β-Tricalcium phosphate scaffold. Cell-scaffold constructs were subjected to different treatment condition and place in either of the bioreactors. Effect of different dynamic conditions on cellular behavior including cell proliferation, cell adhesion and osteogenic differentiation were assessed.Osteogenic assessment of scaffolds after 24 days revealed that rotating & perfusion bioreactor led to significantly higher expression of OCN and RUNX2 genes and also greater amount of ALP and collagen I protein production compared to static groups and perfusion bioreactor. Observation of cellular sheets which filled the scaffold porosities in SEM images, approved the better cell responses to rotating & perfusion forces of the bioreactor. The outcomes demonstrated that rotating & perfusion bioreactor action on bone regeneration is much preferable than perfusion bioreactor. Therefore, it seems that exertion of multi-stimuli is more effective for bone engineering.

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Application of Bioreactors to Improve Functionality of Bone Tissue Engineering Constructs: A Systematic Review

Cited by 17 publications

References 0 publications

Computational modeling of media flow through perfusion-based bioreactors for bone tissue engineering

Computational modeling of media flow through perfusion-based bioreactors for bone tissue engineering

Towards Self‐Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture

Bioreactor cultivation condition for engineered bone tissue: Effect of various bioreactor designs on extra cellular matrix synthesis

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