Mechanistic role of perfusion culture on bone regeneration

Bhaskar, Birru; Mekala, Naveen Kumar; Parcha, Sreenivasa Rao

doi:10.1007/s12038-018-9827-5

Cited by 20 publications

(10 citation statements)

References 55 publications

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“…First, dynamic culture could enhance the mass transport of nutrients and metabolism in the scaffolds and overcome the diffusion limitation of static culture, especially for the central region of the scaffolds [ 24 , 25 ]. Second, fluid flow in dynamic culture generates shear stress acting upon the seeding cells on the scaffolds and further enhances osteogenic differentiation and matrix production [ 8 , 26–28 ]. Nowadays, bioreactors, such as spinner flasks, perfusion systems and rotating wall vessels, are usually used for achieving dynamic culture.…”

Section: Discussionmentioning

confidence: 99%

The effect of macropore size of hydroxyapatite scaffold on the osteogenic differentiation of bone mesenchymal stem cells under perfusion culture

Shi

Xiao

Zhang

et al. 2021

Regenerative Biomaterials

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Previous studies have proved that dynamic culture could facilitate nutrients transport and apply mechanical stimulation to the cells within three-dimensional scaffolds, thus enhancing the differentiation of stem cells towards the osteogenic phenotype. However, the effects of macropore size on osteogenic differentiation of stem cells under dynamic condition are still unclear. Therefore, the objective of this study was to investigate the effects of macropore size of hydroxyapatite (HAp) scaffolds on osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under static and perfusion culture conditions. In vitro cell culture results showed that cell proliferation, alkaline phosphate (ALP) activity, mRNA expression of ALP, collagen-I (Col-I), osteocalcin (OCN) and osteopontin (OPN) were enhanced when cultured under perfusion condition in comparison to static culture. Under perfusion culture condition, the ALP activity and the gene expression of ALP, Col-I, OCN and OPN were enhanced with the macropore size decreasing from 1300 µm to 800 µm. However, with the further decrease in macropore size from 800 µm to 500 µm, the osteogenic related gene expression and protein secretion were reduced. Computational fluid dynamics (CFD) analysis showed that the distribution areas of medium- and high-speed flow increased with the macropore size decreasing, accompanying by the increase of the fluid shear stress within the scaffolds. These results confirm the effects of macropore size on fluid flow stimuli and cell differentiation, and also help optimize the macropore size of HAp scaffolds for bone tissue engineering.

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Section: Discussionmentioning

confidence: 99%

The effect of macropore size of hydroxyapatite scaffold on the osteogenic differentiation of bone mesenchymal stem cells under perfusion culture

Shi

Xiao

Zhang

et al. 2021

Regenerative Biomaterials

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“…The mass transfer through the interconnected pores of the 3D scaffolds and good oxygenation are obtained in the perfusion bioreactor system by the continuous flow of the cell culture medium, enhancing the cell distribution and ECM synthesis. Basic perfusion bioreactors consist of a media reservoir, a tubing circuit, a pump, perfusion/reactor chambers, a waste tank, and an oxygenator or gas-permeable membranes [69,74,94,95]. In the perfusion bioreactor, a medium is piped and next pumped to the reactor chamber contain-ing cells/scaffold constructs.…”

Section: Perfusion Bioreactorsmentioning

confidence: 99%

“…Indirect perfusion occurs when the medium flows around and partly through the biomaterial, whereas direct perfusion indicates the medium flowing only through the biomaterial, thereby shear stress directly influences the cells within the scaffold [69,96,98]. The shear stress stimuli create conditions that mimic the in vivo microenvironment, enhance cell proliferation and differentiation, and also support the mineralization within the bioengineered bone tissue construct [95]. Moreover, Seddiqi et al [99], who determined shear stress-related cell responses in vitro, showed that pulsating fluid flow with high peak shear stress (6.5 Pa) more strongly stimulated nitric oxide production by pre-osteoblasts than fluid flow with low peak shear stress (0.8 Pa).…”

Section: Perfusion Bioreactorsmentioning

confidence: 99%

Bioengineered Living Bone Grafts—A Concise Review on Bioreactors and Production Techniques In Vitro

Kazimierczak

Przekora

2022

IJMS

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It has been observed that bone fractures carry a risk of high mortality and morbidity. The deployment of a proper bone healing method is essential to achieve the desired success. Over the years, bone tissue engineering (BTE) has appeared to be a very promising approach aimed at restoring bone defects. The main role of the BTE is to apply new, efficient, and functional bone regeneration therapy via a combination of bone scaffolds with cells and/or healing promotive factors (e.g., growth factors and bioactive agents). The modern approach involves also the production of living bone grafts in vitro by long-term culture of cell-seeded biomaterials, often with the use of bioreactors. This review presents the most recent findings concerning biomaterials, cells, and techniques used for the production of living bone grafts under in vitro conditions. Particular attention has been given to features of known bioreactor systems currently used in BTE: perfusion bioreactors, rotating bioreactors, and spinner flask bioreactors. Although bioreactor systems are still characterized by some limitations, they are excellent platforms to form bioengineered living bone grafts in vitro for bone fracture regeneration. Moreover, the review article also describes the types of biomaterials and sources of cells that can be used in BTE as well as the role of three-dimensional bioprinting and pulsed electromagnetic fields in both bone healing and BTE.

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“…Perfusion bioreactors are the ones that better simulate in vivo environment by providing a flow of medium to a cell culture, providing oxygen and nutrients through the cell‐seeded scaffolds. [ 14c,171 ] These devices are mostly used in bone [ 172 ] and cartilage tissues [ 173 ] TE approaches, which take advantage of the flow generated shear stress. These devices are reported to provide better outcomes when compared with stirred flask or rotating vessel bioreactors due to higher uniformity in the mixed medium, which allows a better environment and physical stimulation on larger constructs.…”

Section: Physically Active Bioreactors—main Typesmentioning

confidence: 99%

Physically Active Bioreactors for Tissue Engineering Applications

et al. 2020

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Tissue engineering (TE) is a dynamic and growing scientific field that merges the knowledge of different areas such as biology, physics, medicine, and engineering. [1] The TE discipline was first coined at a National Science Foundation sponsored meeting in 1987, thus originating a field that employs life sciences and engineering with the purpose of developing biologic or synthetic supports to restore, keep, or enhance tissue functions or damaged organs. [2] The classical TE approach has been mainly focusing on associating cells with a supporting matrix, also called biomaterials or scaffolds, that essentially acts as a passive template for tissue formation in vitro by allowing cells to adhere, migrate, differentiate, and produce tissue. Usually, the cells are seeded onto the scaffolds and, occasionally, growth factors are also added. The combination of cells, growth factors, and scaffold is often referred as the TE triad. [3] Nevertheless, novel approaches in TE that include the application of a biophysical stimuli to the scaffolds through the use of a bioreactor are emerging. [4] Tissue engineering (TE) is a strongly expanding research area. TE approaches require biocompatible scaffolds, cells, and different applied stimuli, which altogether mimic the natural tissue microenvironment. Also, the extracellular matrix serves as a structural base for cells and as a source of growth factors and biophysical cues. The 3D characteristics of the microenvironment is one of the most recognized key factors for obtaining specific cell responses in vivo, being the physical cues increasingly investigated. Supporting those advances is the progress of smart and multifunctional materials design, whose properties improve the cell behavior control through the possibility of providing specific chemical and physical stimuli to the cellular environment. In this sense, a varying set of bioreactors that properly stimulate those materials and cells in vitro, creating an appropriate biomimetic microenvironment, is developed to obtain active bioreactors. This review provides a comprehensive overview on the important microenvironments of different cells and tissues, the smart materials type used for providing such microenvironments and the specific bioreactor technologies that allow subjecting the cells/ tissues to the required biomimetic biochemical and biophysical cues. Further, it is shown that microfluidic bioreactors represent a growing and interesting field that hold great promise for achieving suitable TE strategies.

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Mechanistic role of perfusion culture on bone regeneration

Cited by 20 publications

References 55 publications

The effect of macropore size of hydroxyapatite scaffold on the osteogenic differentiation of bone mesenchymal stem cells under perfusion culture

The effect of macropore size of hydroxyapatite scaffold on the osteogenic differentiation of bone mesenchymal stem cells under perfusion culture

Bioengineered Living Bone Grafts—A Concise Review on Bioreactors and Production Techniques In Vitro

Physically Active Bioreactors for Tissue Engineering Applications

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