Abstract
Usage of bioreactors in the field of tissue engineering has played a significant role in enabling a controlled and reproducible change in the formation of damaged tissue on being provided with specific factors. Owing to the scarcity seen in providing sufficient donor organs for transplantation there is a huge requirement for large-scale production of artificial organs. This cannot be achieved by static culturing since it does not provide an in-vivo three-dimensional (3D) microenvironment therefore tissue engineering plays a vital role in the development of artificial tissues and organs as per the clinical demands whereas bioreactors have served a major role in providing the artificial microenvironment required by the cells to grow further into a tissue and then into an organ. By providing the specific biochemical cues and mechanoresponsive stimuli the bioreactors turn to be very effective in generating transplantable organs. Apart from performing studies in a controlled manner aimed at understanding biological and physicochemical effects, bioreactors also ensure the safe and reproducible production of tissue-engineered constructs to achieve cost-effective large-scale production. The design criteria for bioreactors to be used in tissue engineering include optimal aspect ratio, proper aeration for the cells to proliferate, and agitation with reduced shear stress. The current review summarizes important aspects like Height/Diameter ratio or aspect ratio, shear stress, mechanical stress, aeration, agitation, oxygenation, etc. related to the design of tissue bioreactors, different types of bioreactors that are in use to date, and the reported pieces of literature to yield an overview on the existing concepts. It mainly focuses on the generation of 3D tissue constructs in various reactor systems specially designed for their culture and development along with their applications.
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Siddiqui, N., B. Kishori, S. Rao, M. Anjum, V. Hemanth, S. Das, and E. Jabbari (2021) Electropsun polycaprolactone fibres in bone tissue engineering: a review. Mol. Biotechnol. 63: 363–388.
Tripathi, S., B. N. Singh, S. Divakar, G. Kumar, S. P. Mallick, and P. Srivastava (2021) Design and evaluation of ciprofloxacin loaded collagen chitosan oxygenating scaffold for skin tissue engineering. Biomed. Mater. 16: 025021.
Mallick, S., Z. Beyene, D. K. Suman, A. Madhual, B. N. Singh, and P. Srivastava (2019) Strategies towards orthopaedic tissue engineered graft generation: current scenario and application. Biotechnol. Bioprocess Eng. 24: 854–869.
Mallick, S. P., D. K. Suman, B. N. Singh, P. Srivastava, N. Siddiqui, V. R. Yella, A. Madhual, and P. K. Vemuri (2020) Strategies toward development of biodegradable hydrogels for biomedical applications. Polym. Plast. Technol. Mater. 59: 911–927.
Athanasiou, V. T., D. J. Papachristou, A. Panagopoulos, A. Saridis, C. D. Scopa, and P. Megas (2010) Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits. Med. Sci. Monit. 16: BR24–BR31.
Mallick, S. P., B. N. Singh, A. Rastogi, and P. Srivastava (2018) Design and evaluation of chitosan/poly(l-lactide)/pectin based composite scaffolds for cartilage tissue regeneration. Int. J. Biol. Macromol. 112: 909–920.
Singh, B. N., V. Veeresh, S. P. Mallick, Y. Jain, S. Sinha, A. Rastogi, and P. Srivastava (2019) Design and evaluation of chitosan/chondroitin sulfate/nano-bioglass based composite scaffold for bone tissue engineering. Int. J. Biol. Macromol. 133: 817–830.
Singh, B. N., V. Veeresh, S. P. Mallick, S. Sinha, A. Rastogi, and P. Srivastava (2020) Generation of scaffold incorporated with nanobioglass encapsulated in chitosan/chondroitin sulfate complex for bone tissue engineering. Int. J. Biol. Macromol. 153: 1–16.
Shick, T. M., A. Z. Abdul Kadir, N. H. A. Ngadiman, and A. Ma’aram (2019) A review of biomaterials scaffold fabrication in additive manufacturing for tissue engineering. J. Bioact. Compat. Polym. 34: 415–435.
Beyene, Z. and R. Ghosh (2019) Effect of zinc oxide addition on antimicrobial and antibiofilm activity of hydroxyapatite: a potential nanocomposite for biomedical applications. Mater. Today Commun. 21: 100612.
Singh, B. N., A. Joshi, S. P. Mallick, and P. Srivastava (2018) Tissue engineering and regenerative medicine: a translational research for antiaging strategy. pp. 47–66. In: S. Rizvi and U. Çakatay (eds.). Molecular Basis and Emerging Strategies for Anti-aging Interventions. Springer, Singapore.
Ali, A., B. N. Singh, S. Yadav, M. Ershad, S. K. Singh, S. P. Mallick, and R. Pyare (2021) CuO assisted borate 1393B3 glass scaffold with enhanced mechanical performance and cyto-compatibility: an in vitro study. J. Mech. Behav. Biomed. Mater. 114: 104231.
Ying, G., N. Jiang, C. Parra-Cantu, G. Tang, J. Zhang, H. Wang, S. Chen, N. P. Huang, J. Xie, and Y. S. Zhang (2020) Bioprinted injectable hierarchically porous gelatin methacryloyl hydrogel constructs with shape-memory properties. Adv. Funct. Mater. 30: 2003740.
Castro, N., S. Ribeiro, M. M. Fernandes, C. Ribeiro, V. Cardoso, V. Correia, R. Minguez, and S. Lanceros-Mendez (2020) Physically active bioreactors for tissue engineering applications. Adv. Biosyst. 4: e2000125.
Yesil-Celiktas, O., A. Gurel, and F. Vardar-Sukan (2010) Large Scale Cultivation of Plant Cell and Tissue Culture in Bioreactors. Transworld Research Network, Trivandrum, India.
Altman, G. H., H. H. Lu, R. L. Horan, T. Calabro, D. Ryder, D. L. Kaplan, P. Stark, I. Martin, J. C. Richmond, and G. Vunjak-Novakovic (2002) Advanced bioreactor with controlled application of multi-dimensional strain for tissue engineering. J. Biomech. Eng. 124: 742–749.
Seddiqi, H., A. Saatchi, G. Amoabediny, M. N. Helder, S. Abbasi Ravasjani, M. Safari Hajat Aghaei, J. Jin, B. Zandieh-Doulabi, and J. Klein-Nulend (2020) Inlet flow rate of perfusion bioreactors affects fluid flow dynamics, but not oxygen concentration in 3D-printed scaffolds for bone tissue engineering: computational analysis and experimental validation. Comput. Biol. Med. 124: 103826.
Swaminathan, V., B. R. Bryant, V. Tchantchaleishvili, and T. K. Rajab (2021) Bioengineering lungs — current status and future prospects. Expert Opin. Biol. Ther. 21: 465–471.
Castilho, L. R. and R. A. Medronho (2002) Cell retention devices for suspended-cell perfusion cultures. Adv. Biochem. Eng. Biotechnol. 74: 129–169.
Martin, Y. and P. Vermette (2005) Bioreactors for tissue mass culture: design, characterization, and recent advances. Biomaterials. 26: 7481–7503.
Borujeni, P. M., E. Ebrahimpoor, and N. Mostoufi (2021) The impact of clearance on mixing time for interface-added substrate. Bioprocess Biosyst. Eng. 44: 701–711.
Kazemzadeh, A., C. Elias, M. Tamer, A. Lohi, and F. Ein-Mozaffari (2020) Mass transfer in a single-use angled-shaft aerated stirred bioreactor applicable for animal cell culture. Chem. Eng. Sci. 219: 115606.
Nienow, A. W. (2021) The impact of fluid dynamic stress in stirred bioreactors — the scale of the biological entity: a personal view. Chem. Ing. Tech. 93: 17–30.
Strobl, F., M. Dürkop, D. Palmberger, and G. Striedner (2020) Reconsider the shear paradigm-stirring and aeration strategies in cell culture processes. https://doi.org/10.21203/rs.3.rs-122078/v1
Li, C., X. Teng, H. Peng, X. Yi, Y. Zhuang, S. Zhang, and J. Xia (2020) Novel scale-up strategy based on three-dimensional shear space for animal cell culture. Chem. Eng. Sci. 212: 115329.
Dusting, J., J. Sheridan, and K. Hourigan (2006) A fluid dynamics approach to bioreactor design for cell and tissue culture. Biotechnol. Bioeng. 94: 1196–1208.
Gelves, R., A. Dietrich, and R. Takors (2014) Modeling of gas-liquid mass transfer in a stirred tank bioreactor agitated by a Rushton turbine or a new pitched blade impeller. Bioprocess Biosyst. Eng. 37: 365–375.
Rameez, S., S. S. Mostafa, C. Miller, and A. A. Shukla (2014) High-throughput miniaturized bioreactors for cell culture process development: reproducibility, scalability, and control. Biotechnol. Prog. 30: 718–727.
Velez-Suberbie, M. L., J. P. Betts, K. L. Walker, C. Robinson, B. Zoro, and E. Keshavarz-Moore (2018) High throughput automated microbial bioreactor system used for clone selection and rapid scale-down process optimization. Biotechnol. Prog. 34: 58–68.
Fenge, C. and E. Lullau (2005) Cell culture bioreactors. pp. 155–224. In: S. S. Ozturk and W.-S. Hu (eds.). Cell Culture Technology for Pharmaceutical and Cell-based Therapies. CRC Press, Boca Raton, FL, USA.
Platas Barradas, O., U. Jandt, L. Da Minh Phan, M. Villanueva, A. Rath, U. Reichl, E. Schräder, S. Scholz, T. Noll, V. Sandig, R. Pörtner, and A. P. Zeng (2011) Criteria for bioreactor comparison and operation standardisation during process development for mammalian cell culture. BMC Proc. 5: P47.
Xing, Z., B. M. Kenty, Z. J. Li, and S. S. Lee (2009) Scale-up analysis for a CHO cell culture process in large-scale bioreactors. Biotechnol. Bioeng. 103: 733–746.
Thomas, B., D. Ohde, S. Matthes, C. Engelmann, P. Bubenheim, K. Terasaka, M. Schlüter, and A. Liese (2021) Comparative investigation of fine bubble and macrobubble aeration on gas utility and biotransformation productivity. Biotechnol. Bioeng. 118: 130–141.
Schmitt, A., J. Mendret, M. Roustan, and S. Brosillon (2020) Ozonation using hollow fiber contactor technology and its perspectives for micropollutants removal in water: a review. Sci. Total Environ. 729: 138664.
Bilodeau, K. and D. Mantovani (2006) Bioreactors for tissue engineering: focus on mechanical constraints. A comparative review. Tissue Eng. 12: 2367–2383.
Galaction, A.-I., R. Ciorap, D. Zaharia, and D. Caşcaval (2009) Bioengineering aspects of tissues culture bioreactors for medicine and environmental applications. Environ. Eng. Manag. J. 8: 195–200.
Bahnemann, J., A. Enders, and S. Winkler (2021) Microfluidic systems and organ (human) on a chip. pp. 175–200. In: C. Kasper, D. Egger, and A. Lavrentieva (eds.). Basic Concepts on 3D Cell Culture. Springer, Cham, Switzerland.
Lone, S. R., V. Kumar, J. R. Seay, D. L. Englert, and H. T. Hwang (2020) Mass transfer and rheological characteristics in a stirred tank bioreactor for cultivation of Escherichia coli BL21. Biotechnol. Bioprocess Eng. 25: 766–776.
Thamer, A. A. and N. A. Issa Alhaboubi (2020) Study the effect of different types impellers on the transfer coefficient in photobioreactor. IOP Conf. Ser. Mater. Sci. Eng. 928: 022144.
Andleeb, S., N. Atiq, M. I. Ali, R. Razi-Ul-Hussnain, M. Shafique, B. Ahmad, P. B. Ghumro, M. Hussain, A. Hameed, and S. Ahmad (2010) Biological treatment of textile effluent in stirred tank bioreactor. Int. J. Agric. Biol. 12: 256–260.
Wang, S. J. and J. J. Zhong (1996) A novel centrifugal impeller bioreactor. I. Fluid circulation, mixing, and liquid velocity profiles. Biotechnol. Bioeng. 51: 511–519.
Amadori, M., G. Volpe, P. Defilippi, and C. Berneri (1997) Phenotypic features of BHK-21 cells used for production of foot-and-mouth disease vaccine. Biologicals. 25: 65–73.
Kretzmer, G. (2002) Industrial processes with animal cells. Appl. Microbiol. Biotechnol. 59: 135–142.
Phillips, A. W., G. D. Ball, K. H. Fantes, N. B. Finter, and M. D. Johnston (1985) Experience in the cultivation of mammalian cells on the 8000 1 scale. pp. 87–95. In: J. Feder and W. R. Tolbert (eds.). Large-Scale Mammalian Cell Culture. Academic Press, Orlando, FL, USA.
Rijken, D. C. and D. Collen (1981) Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J. Biol. Chem. 256: 7035–7041.
Pajić-Lijaković, I., D. Bugarski, M. Plavšić, and B. Bugarski (2007) Influence of microenvironmental conditions on hybridoma cell growth inside the alginate-poly-L-lysine microcapsule. Process Biochem. 42: 167–174.
Zhong, J. J. (2010) Recent advances in bioreactor engineering. Korean J. Chem. Eng. 27: 1035–1041.
Plunkett, N. and F. J. O’Brien (2011) Bioreactors in tissue engineering. Technol. Health Care. 19: 55–69.
Plunkett, N. and F. J. O’Brien (2010) IV.3. Bioreactors in tissue engineering. Stud. Health Technol. Inform. 152: 214–230.
Patil, H., I. S. Chandel, A. K. Rastogi, and P. Srivastava (2013) Studies on a novel bioreactor design for chondrocyte culture. Int. J. Tissue Eng. 2013: 976894.
Nokhbatolfoghahaei, H., M. Bohlouli, Z. Paknejad, M. R. Rad, L. M. Amirabad, N. Salehi-Nik, M. M. Khani, S. Shahriari, N. Nadjmi, A. Ebrahimpour, and A. Khojasteh (2020) Bioreactor cultivation condition for engineered bone tissue: effect of various bioreactor designs on extra cellular matrix synthesis. J. Biomed. Mater. Res. A. 108: 1662–1672.
Bit, A., J. S. Suri, and K. Deskmukh (2020) Bioreactors for tissue engineered blood vessels. pp. 11–30. In: A. Bit and J. S. Suri (eds.). Flow Dynamics and Tissue Engineering of Blood Vessels. IOP Publishing, Bristol, UK.
Bancroft, G N., V. I. Sikavitsas, and A. G. Mikos (2003) Design of a flow perfusion bioreactor system for bone tissue-engineering applications. Tissue Eng. 9: 549–554.
Nokhbatolfoghahaei, H., M. Bohlouli, K. Adavi, Z. Paknejad, M. Rezai Rad, M. M. Khani, N. Salehi-Nik, and A. Khojasteh (2020) Computational modeling of media flow through perfusion-based bioreactors for bone tissue engineering. Proc. Inst. Mech. Eng. H. 234: 1397–1408.
Putame, G., S. Gabetti, D. Carbonaro, F. D. Meglio, V. Romano, A. M. Sacco, I. Belviso, G. Serino, C. Bignardi, U. Morbiducci, C. Castaldo, and D. Massai (2020) Compact and tunable stretch bioreactor advancing tissue engineering implementation. Application to engineered cardiac constructs. Med. Eng. Phys. 84: 1–9.
Mabvuure, N., S. Hindocha, and W. S. Khan (2012) The role of bioreactors in cartilage tissue engineering. Curr. Stem Cell Res. Ther. 7: 287–292.
Schulz, R. M. and A. Bader (2007) Cartilage tissue engineering and bioreactor systems for the cultivation and stimulation of chondrocytes. Eur. Biophys. J. 36: 539–568.
Kuo, C. K., W.-J. Li, R. L. Mauck, and R. S. Tuan (2006) Cartilage tissue engineering: its potential and uses. Curr. Opin. Rheumatol. 18: 64–73.
Martin, I., D. Wendt, and M. Heberer (2004) The role of bioreactors in tissue engineering. Trends Biotechnol. 22: 80–86.
Temenoff, J. S. and A. G. Mikos (2000) Review: tissue engineering for regeneration of articular cartilage. Biomaterials. 21: 431–440.
Eftekhari, A., S. Maleki Dizaj, S. Sharifi, S. Salatin, Y. Rahbar Saadat, S. Zununi Vahed, M. Samiei, M. Ardalan, M. Rameshrad, E. Ahmadian, and M. Cucchiarini (2020) The use of nanomaterials in tissue engineering for cartilage regeneration; current approaches and future perspectives. Int. J. Mol. Sci. 21: 536.
Bramson, M. T. K., S. K. Van Houten, and D. T. Corr (2020) Mechanobiology in soft tissue engineering. pp. 137–159. In: G. L. Niebur (eds.). Mechanobiology: From Molecular Sensing to Disease. Elsevier, Amsterdam, Netherlands.
Bayir, E., M. Sahinler, M. M. Celtikoglu, and A. Sendemir (2020) Bioreactors in tissue engineering: mimicking the microenvironment. pp. 709–752. In: N. E. Vrana, H. Knopf-Marques, and J. Barthes (eds.). Biomaterials for Organ and Tissue Regeneration: New Technologies and Future Prospects. Woodhead Publishing, Oxford, UK.
Grossemy, S., P. P. Chan, and P. M. Doran (2020) Stimulation of cell growth and neurogenesis using protein-functionalized microfibrous scaffolds and fluid flow in bioreactors. Biochem. Eng. J. 159: 107602.
Marlovits, S., B. Tichy, M. Truppe, D. Gruber, and W. Schlegel (2003) Collagen expression in tissue engineered cartilage of aged human articular chondrocytes in a rotating bioreactor. Int. J. Artif. Organs. 26: 319–330.
Chang, C. H., C. C. Lin, C. H. Chou, F. H. Lin, and H. C. Liu (2005) Novel bioreactors for osteochondral tissue engineering. Biomed. Eng. (Singapore). 17: 38–43.
Fernandes Freitas, D. M. (2019) A Mechano-Perfusion Bioreactor for Tissue Engineering. Ph.D. Thesis. University of Girona, Girona, Spain.
Sánchez-Pérez, C., M. E. Fernández-Santos, F. Chana-Rodríguez, J. Vaquero-Martín, D. Crego-Vita, E. Carbó Laso, I. González de Torre, and J. Narbona-Cárceles (2020) In vitro chondral culture under compression and shear stimuli. From mesenchymal stem cells to hyaline cartilage. Rev. Esp. Cir. Ortop. Traumatol. (Engl. Ed.) 64: 380–387.
Li, D., Z. Yin, Y. Liu, S. Feng, Y. Liu, F. Lu, Y. Xu, P. Min, M. Hou, K. Li, A. He, W. Zhang, W. Liu, Y. Zhang, G. Zhou, and Y. Cao (2019) Regeneration of trachea graft with cartilage support, vascularization, and epithelization. Acta Biomater. 89: 206–216.
Shahin, K. and P. M. Doran (2012) Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints. Biotechnol. Bioeng. 109: 1060–1073.
Wendt, D., A. Marsano, M. Jakob, M. Heberer, and I. Martin (2003) Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity. Biotechnol. Bioeng. 84: 205–214.
Tekari, A., R. J. Egli, V. Schmid, J. Justiz, and R. Luginbuehl (2020) A novel bioreactor system capable of simulating the in vivo conditions of synovial joints. Tissue Eng. Part C Methods. 26: 617–627.
Nokhbatolfoghahaei, H., Z. Paknejad, M. Bohlouli, M. Rezai Rad, P. Aminishakib, S. Derakhshan, L. Mohammadi Amirabad, N. Nadjmi, and A. Khojasteh (2020) Fabrication of decellularized engineered extracellular matrix through bioreactor-based environment for bone tissue engineering. ACS Omega. 5: 31943–31956.
Stella, J. A., A. D’Amore, W. R. Wagner, and M. S. Sacks (2010) On the biomechanical function of scaffolds for engineering load-bearing soft tissues. Acta Biomater. 6: 2365–2381.
Ikada, Y. (2011) Tissue Engineering: Fundamentals and Applications. Academic Press/Elsevier, Amsterdam, Netherlands.
Carter, D. R. and M. Wong (2003) Modelling cartilage mechanobiology. Philos. Trans. R. Soc. Lond. B Biol. Sci. 358: 1461–1471.
DuRaine, G. D. and K. A. Athanasiou (2015) ERK activation is required for hydrostatic pressure-induced tensile changes in engineered articular cartilage. J. Tissue Eng. Regen. Med. 9: 368–374.
Toyoda, T., B. B. Seedhom, J. Q. Yao, J. Kirkham, S. Brookes, and W. A. Bonass (2003) Hydrostatic pressure modulates proteoglycan metabolism in chondrocytes seeded in agarose. Arthritis Rheum. 48: 2865–2872.
Correia, C., A. L. Pereira, A. R. Duarte, A. M. Frias, A. J. Pedro, J. T. Oliveira, R. A. Sousa, and R. L. Reis (2012) Dynamic culturing of cartilage tissue: the significance of hydrostatic pressure. Tissue Eng. Part A. 18: 1979–1991.
Wang, W., Q. Deng, T. Li, Y. Liu, Y. Liu, Y. Sun, C. Deng, X. Zhou, Z. Ma, L. Qiang, J. Wang, and K. Dai (2021) Research update on bioreactors used in tissue engineering. J. Shanghai Jiaotong Univ. Sci. 26: 272–283.
Fu, L., P. Li, H. Li, C. Gao, Z. Yang, T. Zhao, W. Chen, Z. Liao, Y. Peng, F. Cao, X. Sui, S. Liu, and Q. Guo (2021) The application of bioreactors for cartilage tissue engineering: advances, limitations, and future perspectives. Stem Cells Int. 2021: 6621806.
Liao, J., X. Guo, K. J. Grande-Allen, F. K. Kasper, and A. G. Mikos (2010) Bioactive polymer/extracellular matrix scaffolds fabricated with a flow perfusion bioreactor for cartilage tissue engineering. Biomaterials. 31: 8911–8920.
Gonçalves, A., P. Costa, M. T. Rodrigues, I. R. Dias, R. L. Reis, and M. E. Gomes (2011) Effect of flow perfusion conditions in the chondrogenic differentiation of bone marrow stromal cells cultured onto starch based biodegradable scaffolds. Acta Biomater. 7: 1644–1652.
Bhardwaj, N., D. Devi, and B. B. Mandal (2015) Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors. Macromol. Biosci. 15: 153–182.
Grab, M., F. Stieglmeier, J. Emrich, L. Grefen, A. Leone, F. König, C. Hagl, and N. Thierfelder (2021) Customized 3D printed bioreactors for decellularization-high efficiency and quality on a budget. Artif. Organs. 45: 1477–1490.
Swaminathan, V., G. Bechtel, and V. Tchantchaleishvili (2021) Artificial tissue creation under microgravity conditions: considerations and future applications. Artif. Organs. 45: 1446–1455.
McCoy, R. J. and F. J. O’Brien (2010) Influence of shear stress in perfusion bioreactor cultures for the development of three-dimensional bone tissue constructs: a review. Tissue Eng. Part B Rev. 16: 587–601.
Szpalski, C., M. Barbara, F. Sagebin, and S. M. Warren (2012) Bone tissue engineering: current strategies and techniques—part II: cell types. Tissue Eng. Part B Rev. 18: 258–269.
Fröhlich, M., W. L. Grayson, D. Marolt, J. M. Gimble, N. Kregar-Velikonja, and G. Vunjak-Novakovic (2010) Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng. Part A. 16: 179–189.
Yang, G., B. Mahadik, J. Y. Choi, J. R. Yu, T. Mollot, B. Jiang, X. He, and J. P. Fisher (2021) Fabrication of centimeter-sized 3D constructs with patterned endothelial cells through assembly of cell-laden microbeads as a potential bone graft. Acta Biomater. 121: 204–213.
Orr, D. E. and K. J. Burg (2008) Design of a modular bioreactor to incorporate both perfusion flow and hydrostatic compression for tissue engineering applications. Ann. Biomed. Eng. 36: 1228–1241.
Mygind, T., M. Stiehler, A. Baatrup, H. Li, X. Zou, A. Flyvbjerg, M. Kassem, and C. Bünger (2007) Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. Biomaterials. 28: 1036–1047.
Stiehler, M., C. Bünger, A. Baatrup, M. Lind, M. Kassem, and T. Mygind (2009) Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells. J. Biomed. Mater. Res. A. 89: 96–107.
Song, C., Z. Guo, Q. Ma, Z. Chen, Z. Liu, H. Jia, and G. Dang (2003) Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochem. Biophys. Res. Commun. 308: 458–462.
Bancroft, G. N., V. I. Sikavitsas, J. van den Dolder, T. L. Sheffield, C. G. Ambrose, J. A. Jansen, and A. G. Mikos (2002) Fluid flow increases mineralized matrix deposition in 3D perfusion culture of marrow stromal osteoblasts in a dose-dependent manner. Proc. Natl. Acad. Sci. U. S. A. 99: 12600–12605.
Jansen, J., E. Ooms, N. Verdonschot, and J. Wolke (2005) Injectable calcium phosphate cement for bone repair and implant fixation. Orthop. Clin. North Am. 36: 89–95, vii.
Xu, X., L. Liao, and W. Tian (2022) Strategies of prevascularization in tissue engineering and regeneration of craniofacial tissues. Tissue Eng. Part B Rev. 28: 464–475.
Yeatts, A. B. and J. P. Fisher (2011) Bone tissue engineering bioreactors: dynamic culture and the influence of shear stress. Bone. 48: 171–181.
Mokhtari-Jafari, F., G. Amoabediny, M. M. Dehghan, S. Abbasi Ravasjani, M. Jabbari Fakhr, and Y. Zamani (2021) Osteogenic and angiogenic synergy of human adipose stem cells and human umbilical vein endothelial cells cocultured in a modified perfusion bioreactor. Organogenesis. 17: 56–71.
Marsell, R. and T. A. Einhorn (2011) The biology of fracture healing. Injury. 42: 551–555.
Masante, B. (2021) Perfusion and Electromagnetic Stimulation Bioreactor for Bone Tissue Engineering: Optimization, Characterization and Validation Tests. Master Thesis. Politecnico di Torino, Torino, Italy.
Huang, Ru-Lin, E. Kobayashi, K. Liu and Q. Li (2016) Bone graft prefabrication following the in vivo bioreactor principle. EBioMedicine. 12: 43–54.
Ikada, Y. (2006) Challenges in tissue engineering. J. R. Soc. Interface. 3: 589–601.
Castro, N., M. M. Fernandes, C. Ribeiro, V. Correia, R. Minguez, and S. Lanceros-Méndez (2020) Magnetic bioreactor for magneto-, mechano- and electroactive tissue engineering strategies. Sensors (Basel). 20: 3340.
Canadas, R. F., A. P. Marques, R. L. Reis, and J. M. Oliveira (2018) Bioreactors and microfluidics for osteochondral interface maturation. Adv. Exp. Med. Biol. 1059: 395–420.
Tanimizu, N., N. Ichinohe, M. Yamamoto, H. Akiyama, Y Nishikawa, and T. Mitaka (2017) Progressive induction of hepatocyte progenitor cells in chronically injured liver. Sci. Rep. 7: 39990.
Allen, J. W., T. Hassanein, and S. N. Bhatia (2001) Advances in bioartificial liver devices. Hepatology. 34: 447–455.
Li, W. J., X. J. Zhu, T. J. Yuan, Z. Y. Wang, Z. Q. Bian, H. S. Jing, X. Shi, C. Y. Chen, G. B. Fu, W. J. Huang, Y. P. Shi, Q. Liu, M. Zeng, H. D. Zhang, H. P. Wu, W. F. Yu, B. Zhai, and H. X. Yan (2020) An extracorporeal bioartificial liver embedded with 3D-layered human liver progenitor-like cells relieves acute liver failure in pigs. Sci. Transl. Med. 12: eaba5146.
Streetz, K. L. (2008) Bio-artificial liver devices—tentative, but promising progress. J. Hepatol. 48: 189–191.
Sauer, I. M., K. Zeilinger, G. Pless, D. Kardassis, T. Theruvath, A. Pascher, M. Goetz, P. Neuhaus, and J. C. Gerlach (2003) Extracorporeal liver support based on primary human liver cells and albumin dialysis-treatment of a patient with primary graft non-function. J. Hepatol. 39: 649–653.
Mavri-Damelin, D., L. H. Damelin, S. Eaton, M. Rees, C. Selden, and H. J. Hodgson (2008) Cells for bioartificial liver devices: the human hepatoma-derived cell line C3A produces urea but does not detoxify ammonia. Biotechnol. Bioeng. 99: 644–651.
Rezania, V., D. Coombe, and J. Tuszynski (2020) Liver bioreactor design issues of fluid flow and zonation, fibrosis, and mechanics: a computational perspective. J. Funct. Biomater. 11: 13.
Arnaout, W. S., A. D. Moscioni, R. L. Barbour, and A. A. Demetriou (1990) Development of bioartificial liver: bilirubin conjugation in Gunn rats. J. Surg. Res. 48: 379–382.
Sussman, N. L., M. G. Chong, T. Koussayer, D. E. He, T. A. Shang, H. H. Whisennand, and J. H. Kelly (1992) Reversal of fulminant hepatic failure using an extracorporeal liver assist device. Hepatology. 16: 60–65.
Flendrig, L. M., J. W. la Soe, G. G. Jörning, A. Steenbeek, O. T. Karlsen, W. M. Bovée, N. C. Ladiges, A. A. te Velde, and R. A. Chamuleau (1997) In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates. J. Hepatol. 26: 1379–1392.
Shito, M., N. H. Kim, H. Baskaran, A. W. Tilles, R. G Tompkins, M. L. Yarmush, and M. Toner (2001) In vitro and in vivo evaluation of albumin synthesis rate of porcine hepatocytes in a flat-plate bioreactor. Artif. Organs. 25: 571–578.
Gerlach, J., T. Trost, C. J. Ryan, M. Meissler, O. Hole, C. Müller, and P. Neuhaus (1994) Hybrid liver support system in a short term application on hepatectomized pigs. Int. J. Artif. Organs. 17: 549–553.
van de Kerkhove, M.-P., E. Di Florio, V. Scuderi, A. Mancini, A. Belli, A. Bracco, M. Dauri, G. Tisone, G. Di Nicuolo, P. Amoroso, A. Spadari, G. Lombardi, R. Hoekstra, F. Calise, and R. A. Chamuleau (2002) Phase I clinical trial with the AMC-bioartificial liver. Int. J. Artif. Organs. 25: 950–959.
Watanabe, F. D., C. J. Mullon, W. R. Hewitt, N. Arkadopoulos, E. Kahaku, S. Eguchi, T. Khalili, W. Arnaout, C. R. Shackleton, J. Rozga, B. Solomon, and A. A. Demetriou (1997) Clinical experience with a bioartificial liver in the treatment of severe liver failure. A phase I clinical trial. Ann. Surg. 225: 484–494.
Zhang, Y., K. Huang, D. Zhu, and L. Li (2021) Hybrid artificial liver. pp. 505–518. In: L. Li (eds.). Artificial Liver. Springer, Singapore.
Sussman, N. L., G. T. Gislason, C. A. Conlin, and J. H. Kelly (1994) The Hepatix extracorporeal liver assist device: initial clinical experience. Artif. Organs. 18: 390–396.
Bao, Q., J. Guo, Y. Chen, F. Yang, and L. Li (2021) Mechanism for the functioning of the artificial liver. pp. 321–378. In: L. Li (eds.). Artificial Liver. Springer, Singapore.
Jinga, M., V. D. Balaban, E. Bontas, and I. C. Tintoiu (2020) Future approaches in liver disorders: regenerative medicine. pp. 811–827. In: F. Radu-Ionita, N. Pyrsopoulos, M. Jinga, I. Tintoiu, Z. Sun, and E. Bontas (eds.). Liver Diseases: A Multidisciplinary Textbook. Springer, Cham, Switzerland.
Sauer, I. M. and J. C. Gerlach (2002) Modular extracorporeal liver support. Artif. Organs. 26: 703–706.
Khaoustov, V. I., G. J. Darlington, H. E. Soriano, B. Krishnan, D. Risin, N. R. Pellis, and B. Yoffe (1999) Induction of three-dimensional assembly of human liver cells by simulated microgravity. In Vitro Cell. Dev. Biol. Anim. 35: 501–509.
Catapano, G. and J. C. Gerlach (2007) Bioreactors for liver tissue engineering. pp. 1–42. In: N. Ashammakhi, R. Reis, and E. Chiellini (eds.). Topics in Tissue Engineering. Vol. 3, Biomaterials and Tissue Engineering Group. https://www.oulu.fi/spareparts/ebook_topics_in_t_e_vol3/abstracts/catapano_01.pdf
Chu, X., K. Korzekwa, R. Elsby, K. Fenner, A. Galetin, Y. Lai, P. Matsson, A. Moss, S. Nagar, G. R. Rosania, J. P. Bai, J. W. Polli, Y. Sugiyama, K. L. Brouwer, and International Transporter Consortium (2013) Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver. Clin. Pharmacol. Ther. 94: 126–141.
Khetani, S. R., D. R. Berger, K. R. Ballinger, M. D. Davidson, C. Lin, and B. R. Ware (2015) Microengineered liver tissues for drug testing. J. Lab. Autom. 20: 216–250.
Chowdhury, S. R., Y. Lokanathan, L. J. Xian, F. M. Busra, M. D. Yazid, N. Sulaiman, G. Lahiry, and M. E. Hoque (2020) 3D printed bioscaffolds for developing tissue-engineered constructs. pp. 187–208. In: E. Yasa, M. Mhadhbi, and E. Santecchia (eds.). Design and Manufacturing. IntechOpen, London, UK.
Grün, C., B. Altmann, and E. Gottwald (2020) Advanced 3D cell culture techniques in micro-bioreactors, part I: a systematic analysis of the literature published between 2000 and 2020. Processes (Basel). 8: 1656.
Sodhi, J. K. and L. Z. Benet (2021) Successful and unsuccessful prediction of human hepatic clearance for lead optimization. J. Med. Chem. 64: 3546–3559.
Wang, A. J. (2020) Engineering Physiologically Relevant In Vitro Liver Models for Inflammation Response and Vascularized Co-Culture. Ph.D. Thesis. Massachusetts Institute of Technology, Cambridge, MA, USA.
Catapano, G., J. K. Unger, E. M. Zanetti, G. Fragomeni, and J. C. Gerlach (2021) Kinetic analysis of lidocaine elimination by pig liver cells cultured in 3D multi-compartment hollow fiber membrane network perfusion bioreactors. Bioengineering (Basel). 8: 104.
Ladd, M. R., S. J. Lee, A. Atala, and J. J. Yoo (2009) Bioreactor maintained living skin matrix. Tissue Eng. Part A. 15: 861–868.
Sun, T., D. Norton, J. W. Haycock, A. J. Ryan, and S. MacNeil (2005) Development of a closed bioreactor system for culture of tissue-engineered skin at an air-liquid interface. Tissue Eng. 11: 1824–1831.
Radtke, A. L. and M. M. Herbst-Kralovetz (2012) Culturing and applications of rotating wall vessel bioreactor derived 3D epithelial cell models. J. Vis. Exp. 62: 3868.
Kalyanaraman, B. and S. Boyce (2007) Assessment of an automated bioreactor to propagate and harvest keratinocytes for fabrication of engineered skin substitutes. Tissue Eng. 13: 983–993.
Selden, C. and B. Fuller (2018) Role ofbioreactor technology in tissue engineering for clinical use and therapeutic target design. Bioengineering (Basel). 5: 32.
Khan, F. and M. Tanaka (2018) Designing smart biomaterials for tissue engineering. Int. J. Mol. Sci. 19: 17.
Lim, D., E. S. Renteria, D. S. Sime, Y. M. Ju, J. H. Kim, T. Criswell, T. D. Shupe, A. Atala, F. C. Marini, M. N. Gurcan, S. Soker, J. Hunsberger, and J. J. Yoo (2022) Bioreactor design and validation for manufacturing strategies in tissue engineering. Biodes. Manuf. 5: 43–63.
Maschmeyer, I., A. K. Lorenz, K. Schimek, T. Hasenberg, A. P. Ramme, J. Hübner, M. Lindner, C. Drewell, S. Bauer, A. Thomas, N. S. Sambo, F. Sonntag, R. Lauster, and U. Marx (2015) A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab. Chip. 15: 2688–2699.
Gangatirkar, P., S. Paquet-Fifield, A. Li, R. Rossi, and P. Kaur (2007) Establishment of 3D organotypic cultures using human neonatal epidermal cells. Nat. Protoc. 2: 178–186.
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Anand, A., Mallick, S.P., Singh, B.N. et al. A Critical Aspect of Bioreactor Designing and Its Application for the Generation of Tissue Engineered Construct: Emphasis on Clinical Translation of Bioreactor. Biotechnol Bioproc E 27, 494–514 (2022). https://doi.org/10.1007/s12257-021-0128-8
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DOI: https://doi.org/10.1007/s12257-021-0128-8