Authors: Taci Pereira, Vice President and General Manager of Bioprinting for 3D Systems, and Yu Shrike Zhang, Assistant Professor at Harvard Medical School, will be participating in Additive Manufacturing Strategies 2022, Panel 1: Current uses of bioprinting.
Bioprinting is the result of applying additive manufacturing to biology. Since its inception, the technology has evolved from the placement of cells in a traditional inkjet printer to complex systems composed of high-end 3D printing methods and sophisticated cell-laden bioactive materials to engineer tissues that recapitulate human physiology. Research progress has been tremendous in areas such as drug development and regenerative medicine as various groups work on pushing the boundaries of what is possible with this platform.
One of the key current uses of bioprinting is the creation of advanced tissue models that reproduce human physiology or pathology for the development of novel therapeutics. The investment required to discover, test, and approve a new drug is estimated to range from $314 million to $2.8 billion . Bioprinting has emerged as a promising method to create highly complex and hence more functional and predictive preclinical models to help solve this pressing issue. We have seen the first published tumor-on-a-chip system that combines a blood and lymphatic vessel pair to better model delivery as well as drainage of anticancer drugs . This is a revolutionary step in better modeling the human complexity to identify the failure of drugs that are bound to fail more quickly, instead of letting rates of clinical trial success remain at 10%.
In addition to drug development, regenerative medicine is a key application area. Since the inception of tissue engineering research, the scientific community has dreamt of the day in which we would be able to 3D bioprint tissues and organs for human implantation. Decades later, this challenge remains. Vascularization is a significant limitation of traditional tissue engineering approaches that can be resolved by using high-resolution bioprinting. Light-based platforms have successfully demonstrated the creation of vessels that enable gas exchange and blood oxygenation, functions that are key for tissue survival . For example, 3D Systems has leveraged these technologies through a partnership with United Therapeutics in an effort to bioprint human lungs. This work has led to the development of the revolutionary Print-to-Perfusion™ process, which has shown promise to enable levels of vascularization not achievable through traditional biofabrication methods.
With the continued development of the field, 3D bioprinting has also seen expansion into unconventional use cases to tackle some of the pressing needs facing its applications. One such development attempts to address the limitation of oxygen supply in engineered tissues by incorporating plant cells into the bioinks that can be co-bioprinted with human cells to create the environment needed for tissue oxygenation [4, 5]. Plant cells can then be selectively removed from the tissue constructs prior to final usage also enabling vascularization to occur with the leftover perfusable microchannel networks. Moreover, a cryobioprinting method utilizing proprietary bioink formulations has been reported to enable simultaneous bioprinting and cryopreservation of tissue constructs, which in turn improves tissue shelf-life for use in production settings . Additional interesting applications scenarios of 3D bioprinting that are being increasingly investigated include but are not limited to those applied to food engineering  and space research .
Over the last two decades or so, the field of 3D bioprinting has seen tremendous advances spanning from hardware/software configurations, such as expanded types of bioprinting methods and enhanced digital controls ; to the bioinks that have been significantly enriched  and their downstream translational applications in various areas . Yet, we see continuing possibilities in further improving the 3D bioprinting technologies primarily from three perspectives. First lies in the potential merge of the different techniques; since each bioprinting modality has its unique advantages and limitations, it is anticipated that the integration of two or more modalities into single ones may lead to extended capacities than each of them separately can attain . Secondly, the combination with artificial intelligence has the potential to open up new avenues to make the bioprinting processes more automated and precise . Finally, miniaturization of 3D bioprinting methods to fit into minimally invasive surgical strategies will make it possible to conduct patient-specific intraoperative procedures to enable more rapid outcomes in areas such as wound healing.
|||O.J. Wouters, M. McKee, J. Luyten, “Estimated research and development investment needed to bring a new medicine to market, 2009-2018,” JAMA, pp. 844-853, 2020.|
|||X. Cao, R. Ashfaq, F. Cheng, S. Maharjan, J. Li, G. Ying, S. Hassan, H. Xiao, K. Yue, Y.S. Zhang, “A Tumor-on-a-Chip System with Bioprinted Blood and Lymphatic Vessel Pair,” Advanced Functional Materials, 2019.|
|||B. Grigoryan, S. J. Paulsen, D.C. Corbett, D.W. Sazer, C. L. Fortin, A.J. Zaita, P.T. Greenfield, N.J. Calafat, J.P. Gounley, J.S. Miller, “Multivascular Networks and Functional Intravascular Topologies within Biocompatible Hydrogels,” Science, 2019.|
|||A. Lode, F. Krujatz, S. Brüggemeier, M. Quade, K. Schütz, S. Knaack, J. Weber, T. Bley, M. Gelinsky, “Green bioprinting: Fabrication of photosynthetic algae‐laden hydrogel scaffolds for biotechnological and medical applications,” Wiley Online Library, 2015.|
|||S. Maharjan, J. Alva, C. Cámara, A.G. Rubio, D. Hernández, C. Delavaux, E. Correa, M.D. Romo, D. Bonilla, M.L. Santiago, W. Li, F. Cheng, G. Ying, Y.S. Zhang, “Symbiotic Photosynthetic Oxygenation within 3D-Bioprinted Vascularized Tissues,” Matter, vol. 4, pp. 217-240, 2021.|
|||H. Ravanbakhsh, Z. Luo, X. Zhang, S. Maharjan, H.S. Mirkarimi, G. Tang, C. Chávez-Madero, L. Mongeau, Y.S. Zhang, “Freeform cell-laden cryobioprinting for shelf-ready tissue fabrication and storage,” Matter, 2022.|
|||C.K. Chua, “Publication Trends in 3D Bioprinting and 3D Food Printing,” International Journal of Bioprinting, vol. 6, no. 1, pp. 1-3, 2020.|
|||L. Moroni, K. Tabury, H. Stenuit, D. Grimm, S. Baatout, V. Mironov, “What can biofabrication do for space and what can space do for biofabrication?,” Trends in Biotechnology, 2021.|
|||C.E. Garciamendez-Mijares, P. Agrawal, G. García Martínez, E. Cervantes Juarez, Y.S. Zhang, “State-of-art affordable bioprinters: A guide for the DiY community,” Applied Physics Reviews, vol. 8, 2021.|
|||Y.S. Zhang, “Biomaterial Inks,” Advanced Healthcare Materials, vol. 9, no. 15, 2020.|
|||A.C. Daly, M.E. Prendergast, A.J. Hughes, J.A. Burdick, “Bioprinting for the Biologist,” Cell, vol. 184, no. 1, pp. 18-32, 2021.|
|||R. Levato, T. Jungst, R.G. Scheuring, T. Blunk, J. Groll, J. Malda, “From shape to function: the next step in bioprinting,” Advanced Materials, vol. 32, no. 12, 2020.|
|||Z. Zhu, D.W.H. Ng, H.S. Park, M.C. McAlpine, “3D-printed multifunctional materials enabled by artificial-intelligence-assisted fabrication technologies,” Nature Reviews Materials, vol. 6, pp. 27-47, 2020.|
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