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1. Chaotic printing: using chaos to fabricate densely packed micro- and nanostructures at high resolution and speed

Author

Trujillo-de Santiago, Grissel, Alvarez, Mario Moises, Samandari, Mohamadmahdi, Prakash, Gyan, Chandrabhatla, Gouri, Rellstab-Sanchez, Pamela Ines, Byambaa, Batzaya, Abadi, Parisa Pour Shahid Saeed, Mandla, Serena, Avery, Reginald K, Vallejo-Arroyo, Alejandro, Nasajpour, Amir, Annabi, Nasim, Zhang, Yu Shrike, and Khademhosseini, Ali

Subjects
Bioengineering
Abstract

Chaotic flows are used to rapidly fabricate densely packed lamellar micro- and nanostructure that is then preserved by curing or photocrosslinking.

Published
2018

2. Visible light crosslinkable human hair keratin hydrogels.

Author

Yue, Kan, Liu, Yanhui, Byambaa, Batzaya, Singh, Vaishali, Liu, Wanjun, Li, Xiuyu, Sun, Yunxia, Zhang, Yu Shrike, Tamayol, Ali, Zhang, Peihua, Ng, Kee Woei, Annabi, Nasim, and Khademhosseini, Ali

Subjects
compounds/materials, regenerative medicine, tissue engineering
Abstract

Keratins extracted from human hair have emerged as a promising biomaterial for various biomedical applications, partly due to their wide availability, low cost, minimal immune response, and the potential to engineer autologous tissue constructs. However, the fabrication of keratin-based scaffolds typically relies on limited crosslinking mechanisms, such as via physical interactions or disulfide bond formation, which are time-consuming and result in relatively poor mechanical strength and stability. Here, we report the preparation of photocrosslinkable keratin-polyethylene glycol (PEG) hydrogels via the thiol-norbornene "click" reaction, which can be formed within one minute upon irradiation of visible light. The resulting keratin-PEG hydrogels showed highly tunable mechanical properties of up to 45 kPa in compressive modulus, and long-term stability in buffer solutions and cell culture media. These keratin-based hydrogels were tested as cell culture substrates in both two-dimensional surface seeding and three-dimensional cell encapsulation, demonstrating excellent cytocompatibility to support the attachment, spreading, and proliferation of fibroblast cells. Moreover, the photocrosslinking mechanism makes keratin-based hydrogel suitable for various microfabrication techniques, such as micropatterning and wet spinning, to fabricate cell-laden tissue constructs with different architectures. We believe that the unique features of this photocrosslinkable human hair keratin hydrogel promise new opportunities for their future biomedical applications.

Published
2018

3. Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue

Author

Byambaa, Batzaya, Annabi, Nasim, Yue, Kan, Santiago, Grissel Trujillo‐de, Alvarez, Mario Moisés, Jia, Weitao, Kazemzadeh‐Narbat, Mehdi, Shin, Su Ryon, Tamayol, Ali, and Khademhosseini, Ali

Subjects
Bioengineering, Transplantation, Stem Cell Research, Regenerative Medicine, Biotechnology, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Bioprinting, Bone and Bones, Cell Line, Cell Survival, Coculture Techniques, Human Umbilical Vein Endothelial Cells, Humans, Hydrogel, Polyethylene Glycol Dimethacrylate, Mesenchymal Stem Cells, Neovascularization, Physiologic, Osteogenesis, Tissue Engineering, Tissue Scaffolds, Vascular Endothelial Growth Factor A, 3D bioprinting, angiogenic hydrogels, bone-like tissue constructs, vascularized bone tissue, Medicinal and Biomolecular Chemistry, Biomedical Engineering, Medical Biotechnology
Abstract

Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMALOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs.

Published
2017

4. Engineering Photocrosslinkable Bicomponent Hydrogel Constructs for Creating 3D Vascularized Bone

Author

Kazemzadeh‐Narbat, Mehdi, Rouwkema, Jeroen, Annabi, Nasim, Cheng, Hao, Ghaderi, Masoumeh, Cha, Byung‐Hyun, Aparnathi, Mansi, Khalilpour, Akbar, Byambaa, Batzaya, Jabbari, Esmaiel, Tamayol, Ali, and Khademhosseini, Ali

Subjects
Engineering, Biomedical Engineering, Dental/Oral and Craniofacial Disease, Transplantation, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Stem Cell Research, Bioengineering, Musculoskeletal, Animals, Bone Regeneration, Humans, Hydrogels, Nanoparticles, Osteogenesis, Tissue Engineering, bone tissue engineering, hydrogels, micropatterning, vascularization, Medicinal and Biomolecular Chemistry, Medical Biotechnology, Medical biotechnology, Biomedical engineering
Abstract

Engineering bone tissue requires the generation of a highly organized vasculature. Cellular behavior is affected by the respective niche. Directing cellular behavior and differentiation for creating mineralized regions surrounded by vasculature can be achieved by controlling the pattern of osteogenic and angiogenic niches. This manuscript reports on engineering vascularized bone tissues by incorporating osteogenic and angiogenic cell-laden niches in a photocrosslinkable hydrogel construct. Two-step photolithography process is used to control the stiffness of the hydrogel and distribution of cells in the patterned hydrogel. In addittion, osteoinductive nanoparticles are utilized to induce osteogenesis. The size of microfabricated constructs has a pronounced effect on cellular organization and function. It is shown that the simultaneous presence of both osteogenic and angiogenic niches in one construct results in formation of mineralized regions surrounded by organized vasculature. In addition, the presence of angiogenic niche improves bone formation. This approach can be used for engineered constructs that can be used for treatment of bone defects.

Published
2017

6. List of contributors

Author

Abe, Masashi, primary, Ahlstrom, Jon D., additional, Albon, Julie, additional, Allickson, Julie, additional, Almeida-Porada, Graça, additional, Altschuler, Richard A., additional, Anderson, Daniel G., additional, Annabi, Nasim, additional, Arcidiacono, Judith, additional, Ashammakhi, Nureddin, additional, Atala, Anthony, additional, Athanasiou, Kyriacos A., additional, Awad, Hani A., additional, Badylak, Stephen F, additional, Balachander, Gowri, additional, Balkan, Wayne, additional, Bara, Jennifer J., additional, Barry, Michael P., additional, Baskaran, Harihara, additional, Bedell, Matthew L., additional, Belcher, Donald Andrew, additional, Berry, David B., additional, Bhat, Hina, additional, Bhat, Zuhaib F., additional, Bhatia, Sangeeta N., additional, Blackburn, Catherine Clare, additional, Blocki, Anna, additional, Blum, Kevin M., additional, Bochenek, Matthew A., additional, Bonassar, Lawrence J., additional, Bonventre, Joseph V., additional, Borrelli, Mimi R., additional, Bowles, Robby D., additional, Bradshaw, Amy D., additional, Bratt-Leal, Andres M., additional, Breuer, Christopher K., additional, Brewster, Luke, additional, Brey, Eric M., additional, Briquez, Priscilla S., additional, Buckwalter, J.A., additional, Burg, Karen J.L., additional, Burg, Timothy C., additional, Byambaa, Batzaya, additional, Chandra, Prafulla K., additional, Chen, Amanda X., additional, Chen, Fa-Ming, additional, Chen, Shaochen, additional, Chesterman, Julian, additional, Chhabra, Arnav, additional, Chong, Seow Khoon, additional, Clark, Richard A.F., additional, Cleary, Muriel A., additional, Coleman, M., additional, Cotsarelis, George, additional, Crystal, Ronald G., additional, Dagnelie, Gislin, additional, Darabi, Mohammad Ali, additional, Davidson, Jeffrey M., additional, Davidson, Joseph, additional, De Coppi, Paolo, additional, Delcassian, Derfogail, additional, de Vos, Paul, additional, Dominijanni, Anthony, additional, Donahue, Ryan, additional, Drain, Allison P., additional, Duvall, Craig L., additional, Dziki, Jenna L., additional, Elgalad, Abdelmotagaly, additional, Eng, George, additional, Falanga, Vincent, additional, Farhang, Niloofar, additional, Ferreira, Lino, additional, Fink, Donald W., additional, Fleming, Heather E., additional, Fong, Peter, additional, Frey, Mark R., additional, Gay, Denise, additional, Gerecht, Sharon, additional, Gersbach, Charles A., additional, Gibbs, D.M.R., additional, Gidwani, Simran, additional, González Morales, Shaimar R., additional, Goyal, Ritu, additional, Grant, Maria B., additional, Gray, Andrea, additional, Greisler, Howard P., additional, Grikscheit, Tracy C., additional, Grosh, Karl, additional, Guilak, Farshid, additional, Guo, Jason L., additional, Han, Yingli, additional, Hare, Joshua M., additional, Hassanbhai, Ammar Mansoor, additional, Hatzistergos, Konstantinos, additional, Hay, David C., additional, He, Xiao-Tao, additional, Henderson, Timothy, additional, Hickerson, Darren, additional, Hickerson, Darren H.M., additional, Hmadcha, Abdelkrim, additional, Hochman-Mendez, Camila, additional, Huang, Chao, additional, Hubbell, Jeffrey A., additional, Huelsmann, Joern, additional, Huh, Jun Tae, additional, Hunsberger, Joshua G., additional, Iannucci, Leanne E., additional, Inoue, Haruhisa, additional, Jackson, John, additional, Jiang, Yangzi, additional, Kalinichenko, Vladimir V., additional, Kanczler, J.M., additional, Karp, Jeffrey M., additional, Kasper, F. Kurtis, additional, Khademhosseini, Ali, additional, Kim, Ji Hyun, additional, Kimbrel, Erin A., additional, Klimanskaya, Irina, additional, Kohn, Joachim, additional, Kumar, Sunil, additional, Kyriakides, Themis R., additional, Lake, Spencer P., additional, Lam, Johnny, additional, Langer, Robert, additional, Lanza, Robert, additional, Leach, Timothy S., additional, Lee, Benjamin W., additional, Lee, Iris, additional, Lee, Sang Jin, additional, Li, David, additional, Li, Linheng, additional, Liu, Qian, additional, Ljubimov, Alexander V., additional, Lo, Chi, additional, Longaker, Michael T., additional, López-Beas, Javier, additional, Loring, Jeanne F., additional, Luo, Ying, additional, MacArthur, Ben D., additional, Madigan, Nicolas N., additional, Madry, Henning, additional, Magalhaes, Renata S., additional, Manley, Nancy Ruth, additional, Mansbridge, Jonathan, additional, Mao, Jeremy J., additional, Marshall, K.M., additional, Martin, J.A., additional, Martins-Green, M., additional, Maselli, Kathryn M., additional, Maxfield, Mark W., additional, McCracken, Kyle W., additional, Melville, James, additional, Mikos, Antonios G., additional, Millán, José del R., additional, Mirotsou, Maria, additional, Montoro, Daniel T., additional, Murphy, Matthew P., additional, Murphy, Sean V., additional, Musillo, Michael, additional, Muthukumaran, Padmalosini, additional, Navara, Adam M., additional, Nelson, Christopher E., additional, Niklason, Laura E., additional, Nowell, Craig Scott, additional, O’Keefe, Regis J., additional, O’Neill, Kathy E., additional, Oreffo, Richard O.C., additional, Ortiz, Ophir, additional, Palmer, Andre Francis, additional, Perdikis, Serafeim, additional, Petreaca, M., additional, Plikus, Maksim V., additional, Porada, Christopher D., additional, Post, Mark, additional, Prokop, Aleš, additional, Puri, Raj K., additional, Qian, Pengxu, additional, Radisic, Milica, additional, Raredon, Micha Sam Brickman, additional, Richie, Ellen Rothman, additional, Rouse, Paul, additional, Sadri-Ardekani, Hooman, additional, Saltzman, W. Mark, additional, Sampaio, Luiz C., additional, Schlieve, Christopher R., additional, Sha, Su-Hua, additional, Sharpe, Paul T., additional, Shastri, V. Prasad, additional, Shi, Yanhong, additional, Shupe, Thomas, additional, Sirabella, Dario, additional, Skardal, Aleksander, additional, Slack, J.M.W., additional, Sloan, Stephen R., additional, Soker, Shay, additional, Soria, Bernat, additional, Soria-Juan, Bárbara, additional, Stockdale, Frank E., additional, Stover, Josh, additional, Stransky, Thomas, additional, Stronks, H. Christiaan, additional, Stumpf, Patrick S., additional, Sung, Kyung Eun, additional, Swarr, Daniel, additional, Szkolnicka, Dagmara, additional, Takahashi, Jun, additional, Tang, D.K.O., additional, Tang, Winson, additional, Taylor, Doris A., additional, Teng, Yao, additional, Teoh, Swee Hin, additional, Smith, Anthony J., additional, Treffeisen, Elsa, additional, Tuan, Rocky S., additional, Vacanti, Joseph P., additional, van der Weele, Cor, additional, Vincent, Matthew, additional, Vunjak-Novakovic, Gordana, additional, Wahlberg, Lars U., additional, Wan, Derrick C., additional, Wang, Anne, additional, Wang, Dan, additional, Wang, Qiwei, additional, Wang, Yanling, additional, Wang, Yu-li, additional, Wang, Zhanwen, additional, Weaver, Valerie M., additional, Wells, J.A., additional, Welter, Jean F., additional, Wen, Feng, additional, Weston, Jake, additional, Whitsett, Jeffrey A., additional, Williams, James K., additional, Windebank, Anthony J., additional, Wong, Mark Eu-Kien, additional, Worgall, Stefan, additional, Wu, Iwen, additional, Wu, Rui-Xin, additional, Xie, Virginia Y., additional, Xing, Malcolm, additional, Yamada, Kenneth M., additional, Yamanaka, Shinya, additional, Yoo, James J., additional, Young, Simon, additional, Yu, Claire, additional, Yu, Hanry, additional, Yuan, Yifan, additional, Zacharias, William, additional, Zakko, Jason, additional, Zhang, Ai, additional, Zhang, Yuanyuan, additional, Zhang, Zheng, additional, Zhao, Chunfeng, additional, Zhao, Yimu, additional, and Zoloth, Laurie, additional

Published
2020
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9. Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA

Author

Elkhoury, Kamil, primary, Chen, Mo, additional, Koçak, Polen, additional, Enciso-Martínez, Eduardo, additional, Bassous, Nicole Joy, additional, Lee, Myung Chul, additional, Byambaa, Batzaya, additional, Rezaei, Zahra, additional, Li, Yang, additional, Ubina López, María Elizabeth, additional, Gurian, Melvin, additional, Sobahi, Nebras, additional, Hussain, Mohammad Asif, additional, Sanchez-Gonzalez, Laura, additional, Leijten, Jeroen, additional, Hassan, Shabir, additional, Arab-Tehrany, Elmira, additional, Ward, Jennifer Ellis, additional, and Shin, Su Ryon, additional

Published
2022
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12. Smart wound scaffolds: light-controlled growth factors release on tetrapodal ZnO-Incorporated 3D-printed hydrogels for developing smart wound scaffold

Author

Siebert, Leonard, Luna-Cerón, Eder, García-Rivera, Luis Enrique, Oh, Junsung, Jang, JunHwee, Mishra, Yogendra Kumar, Rosas-Gómez, Diego A., Pérez-Gómez, Mitzi D., Maschkowitz, Gregor, Fickenscher, Helmut, Oceguera-Cuevas, Daniela, Holguín-León, Carmen G., Byambaa, Batzaya, Hussain, Mohammad A., Enciso-Martínez, Eduardo, Cho, Minsung, Lee, Yuhan, Sobahl, Nebras, Hasan, Anwarul, P. Orgill, Dennis, Adelungd, Rainer, Lee, Eunjung, and Shin, Su Ryon

Subjects
integumentary system, humanities
Abstract

n article number 2007555, Leonard Siebert, Eunjung Lee, Su Ryon Shin, and co-workers develop a 3D printed smart wound scaffold encapsulating growth factors decorated with light-sensitive and antibacterial tetrapodal zinc oxide (t-ZnO) microparticles for the treatment of chronic wounds. The multifunctional pro perties of the smart scaffold combined with light-triggered angiogenic factor release, antibacterial properties, and tissue compatibility enable fast wound recovery.

Published
2021

13. Smart Wound Scaffolds: Light‐Controlled Growth Factors Release on Tetrapodal ZnO‐Incorporated 3D‐Printed Hydrogels for Developing Smart Wound Scaffold (Adv. Funct. Mater. 22/2021)

Author

Siebert, Leonard, primary, Luna‐Cerón, Eder, additional, García‐Rivera, Luis Enrique, additional, Oh, Junsung, additional, Jang, JunHwee, additional, Rosas‐Gómez, Diego A., additional, Pérez‐Gómez, Mitzi D., additional, Maschkowitz, Gregor, additional, Fickenscher, Helmut, additional, Oceguera‐Cuevas, Daniela, additional, Holguín‐León, Carmen G., additional, Byambaa, Batzaya, additional, Hussain, Mohammad A., additional, Enciso‐Martínez, Eduardo, additional, Cho, Minsung, additional, Lee, Yuhan, additional, Sobahi, Nebras, additional, Hasan, Anwarul, additional, Orgill, Dennis P., additional, Mishra, Yogendra Kumar, additional, Adelung, Rainer, additional, Lee, Eunjung, additional, and Shin, Su Ryon, additional

Published
2021
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15. Recent advances in 3D bioprinting of musculoskeletal tissues

Author

Potyondy, Tyler, primary, Uquillas, Jorge Alfredo, additional, Tebon, Peyton J, additional, Byambaa, Batzaya, additional, Hasan, Anwarul, additional, Tavafoghi, Maryam, additional, Mary, Heloise, additional, Aninwene, George E, additional, Pountos, Ippokratis, additional, Khademhosseini, Ali, additional, and Ashammakhi, Nureddin, additional

Published
2021
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16. Light‐Controlled Growth Factors Release on Tetrapodal ZnO‐Incorporated 3D‐Printed Hydrogels for Developing Smart Wound Scaffold

Author

Siebert, Leonard, primary, Luna‐Cerón, Eder, additional, García‐Rivera, Luis Enrique, additional, Oh, Junsung, additional, Jang, JunHwee, additional, Rosas‐Gómez, Diego A., additional, Pérez‐Gómez, Mitzi D., additional, Maschkowitz, Gregor, additional, Fickenscher, Helmut, additional, Oceguera‐Cuevas, Daniela, additional, Holguín‐León, Carmen G., additional, Byambaa, Batzaya, additional, Hussain, Mohammad A., additional, Enciso‐Martínez, Eduardo, additional, Cho, Minsung, additional, Lee, Yuhan, additional, Sobahi, Nebras, additional, Hasan, Anwarul, additional, Orgill, Dennis P., additional, Mishra, Yogendra Kumar, additional, Adelung, Rainer, additional, Lee, Eunjung, additional, and Shin, Su Ryon, additional

Published
2021
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18. Advancing Frontiers in Bone Bioprinting

Author

Ashammakhi, Nureddin, primary, Hasan, Anwarul, additional, Kaarela, Outi, additional, Byambaa, Batzaya, additional, Sheikhi, Amir, additional, Gaharwar, Akhilesh K., additional, and Khademhosseini, Ali, additional

Published
2019
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19. Porous Electrospun Fibers With Self-Sealing Functionality: An Enabling Strategy For Trapping Biomacromolecules

Author

Zhang, Jin, Zheng, Ting, Alarcin, Emine, Byambaa, Batzaya, Guan, Xiaofei, Ding, Jianxun, Zhang, Yu Shrike, and Li, Zhongming

Abstract

Stimuli-responsive porous polymer materials have promising biomedical application due to their ability to trap and release biomacromolecules. In this work, a class of highly porous electrospun fibers is designed using polylactide as the polymer matrix and poly(ethylene oxide) as a porogen. Carbon nanotubes (CNTs) with different concentrations are further impregnated onto the fibers to achieve self-sealing functionality induced by photothermal conversion upon light irradiation. The fibers with 0.4 mg mL(-1) of CNTs exhibit the optimum encapsulation efficiency of model biomacromolecules such as dextran, bovine serum albumin, and nucleic acids, although their photothermal conversion ability is slightly lower than the fibers with 0.8 mg mL(-1) of CNTs. Interestingly, reversible reopening of the surface pores is accomplished with the degradation of PLA, affording a further possibility for sustained release of biomacromolecules after encapsulation. Effects of CNT loading on fiber morphology, structure, thermal/mechanical properties, degradation, and cell viability are also investigated. This novel class of porous electrospun fibers with self-sealing capability has great potential to serve as an enabling strategy for trapping/release of biomacromolecules with promising applications in, for example, preventing inflammatory diseases by scavenging cytokines from interstitial body fluids.

Published
2017

23. Engineering Photocrosslinkable Bicomponent Hydrogel Constructs for Creating 3D Vascularized Bone.

Author

Kazemzadeh-Narbat, Mehdi, Kazemzadeh-Narbat, Mehdi, Rouwkema, Jeroen, Annabi, Nasim, Cheng, Hao, Ghaderi, Masoumeh, Cha, Byung-Hyun, Aparnathi, Mansi, Khalilpour, Akbar, Byambaa, Batzaya, Jabbari, Esmaiel, Tamayol, Ali, Khademhosseini, Ali, Kazemzadeh-Narbat, Mehdi, Kazemzadeh-Narbat, Mehdi, Rouwkema, Jeroen, Annabi, Nasim, Cheng, Hao, Ghaderi, Masoumeh, Cha, Byung-Hyun, Aparnathi, Mansi, Khalilpour, Akbar, Byambaa, Batzaya, Jabbari, Esmaiel, Tamayol, Ali, and Khademhosseini, Ali

Abstract

Engineering bone tissue requires the generation of a highly organized vasculature. Cellular behavior is affected by the respective niche. Directing cellular behavior and differentiation for creating mineralized regions surrounded by vasculature can be achieved by controlling the pattern of osteogenic and angiogenic niches. This manuscript reports on engineering vascularized bone tissues by incorporating osteogenic and angiogenic cell-laden niches in a photocrosslinkable hydrogel construct. Two-step photolithography process is used to control the stiffness of the hydrogel and distribution of cells in the patterned hydrogel. In addittion, osteoinductive nanoparticles are utilized to induce osteogenesis. The size of microfabricated constructs has a pronounced effect on cellular organization and function. It is shown that the simultaneous presence of both osteogenic and angiogenic niches in one construct results in formation of mineralized regions surrounded by organized vasculature. In addition, the presence of angiogenic niche improves bone formation. This approach can be used for engineered constructs that can be used for treatment of bone defects.

Published
2017

24. Hybrid Microscopy: Enabling Inexpensive High-Performance Imaging through Combined Physical and Optical Magnifications

Author

Byambaa Batzaya, Mehmet R. Dokmeci, Aishwarya Aravamudhan Ramanujam, Mario Moises Alvarez, Paul W. Tillberg, Grissel Trujillo-de Santiago, Fei Chen, Jae-Byum Chang, Mehdi Kazemzadeh-Narbat, Vaishali Krishnadoss, Julio Aleman, Ali Khademhosseini, Edward S. Boyden, Yu Shrike Zhang, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Media Laboratory, Massachusetts Institute of Technology. Microsystems Technology Laboratories, McGovern Institute for Brain Research at MIT, Program in Media Arts and Sciences (Massachusetts Institute of Technology), Massachusetts Institute of Technology. Center for Neurobiological Engineering, Zhang, Yu Shrike, Chang, Jae-Byum, Alvarez, Mario Moises, Trujillo de Santiago, Grissel, Aleman, Julio, Batzaya, Byambaa, Krishnadoss, Vaishali, Ramanujam, Aishwarya Aravamudhan, Kazemzadeh-Narbat, Mehdi, Chen, Fei, Tillberg, Paul W., Dokmeci, Mehmet R., Boyden, Edward, and Khademhosseini, Alireza

Subjects
0301 basic medicine, Microscope, Computer science, Orders of magnitude (temperature), Cost-Benefit Analysis, Magnification, Mice, Transgenic, Article, law.invention, 03 medical and health sciences, Mice, Optics, law, Tubulin, Microscopy, Animals, Humans, Instrumentation (computer programming), Luminescent Proteins, Multidisciplinary, Microscopy, Confocal, business.industry, Brain, Reproducibility of Results, Fluorescence, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, Microscopy, Fluorescence, NIH 3T3 Cells, business
Abstract

To date, much effort has been expended on making high-performance microscopes through better instrumentation. Recently, it was discovered that physical magnification of specimens was possible, through a technique called expansion microscopy (ExM), raising the question of whether physical magnification, coupled to inexpensive optics, could together match the performance of high-end optical equipment, at a tiny fraction of the price. Here we show that such “hybrid microscopy” methods—combining physical and optical magnifications—can indeed achieve high performance at low cost. By physically magnifying objects, then imaging them on cheap miniature fluorescence microscopes (“mini-microscopes”), it is possible to image at a resolution comparable to that previously attainable only with benchtop microscopes that present costs orders of magnitude higher. We believe that this unprecedented hybrid technology that combines expansion microscopy, based on physical magnification, and mini-microscopy, relying on conventional optics—a process we refer to as Expansion Mini-Microscopy (ExMM)—is a highly promising alternative method for performing cost-effective, high-resolution imaging of biological samples. With further advancement of the technology, we believe that ExMM will find widespread applications for high-resolution imaging particularly in research and healthcare scenarios in undeveloped countries or remote places., National Institutes of Health (U.S.) (EB012597), National Institutes of Health (U.S.) (AR057837), National Institutes of Health (U.S.) (DE021468), National Institutes of Health (U.S.) (HL099073), National Institutes of Health (U.S.) (R56AI105024), United States. Office of Naval Research. Young Investigator Program, Presidential Early Career Award for Scientists and Engineers, MIT International Science and Technology Initiatives, Massachusetts Institute of Technology. Media Laboratory, National Institutes of Health (U.S.) (Transformative Award NIH 1R01MH103910), National Institutes of Health (U.S.) (Transformative Award NIH 1U01MH106011), National Institutes of Health (U.S.) (Director’s Pioneer Award 1DP1NS087724), New York Stem Cell Foundation (New York Stem Cell Foundation-Robertson Award), Simons Foundation

Published
2016
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