They have a unique strategy for vascularization of hydrogel constructs that combine advances in 3D bioprinting technology and biomaterials.
The researchers first used a 3D bioprinter to make an agarose (naturally derived sugar-based molecule) fiber template to serve as the mold for the blood vessels. They then covered the mold with a gelatin-like substance called hydrogel, forming a cast over the mold which was then reinforced via photocrosslinks.
Artificial blood vessels are created using hydrogel constructs that combine advances in 3-D bioprinting technology and biomaterials. Credit: Khademhosseini Lab.
"Our approach involves the printing of agarose fibers that become the blood vessel channels. But what is unique about our approach is that the fiber templates we printed are strong enough that we can physically remove them to make the channels," said Khademhosseini. "This prevents having to dissolve these template layers, which may not be so good for the cells that are entrapped in the surrounding gel."
Khademhosseini and his team were able to construct microchannel networks exhibiting various architectural features. They were also able to successfully embed these functional and perfusable microchannels inside a wide range of commonly used hydrogels, such as methacrylated gelatin or poly(ethylene glycol)-based hydrogels at different concentrations.
See the long list of articles and successes with tissue engineering from the Khademhosseini lab.
A previous approach with untethered magnetic microrobots
Previously in February, 2014 : Researchers at Brigham and Women's Hospital (BWH) and Carnegie Mellon University have introduced a unique micro-robotic technique to assemble the components of complex materials, the foundation of tissue engineering and 3D printing.
The presented approach uses untethered magnetic micro-robotic coding for precise construction of individual cell-encapsulating hydrogels (such as cell blocks). The micro-robot, which is remotely controlled by magnetic fields, can move one hydrogel at a time to build structures. This is critical in tissue engineering, as human tissue architecture is complex, with different types of cells at various levels and locations. When building these structures, the location of the cells is significant in that it will impact how the structure will ultimately function. "Compared with earlier techniques, this technology enables true control over bottom-up tissue engineering," explains Tasoglu.
Tasoglu and Demirci also demonstrated that micro-robotic construction of cell-encapsulating hydrogels can be performed without affecting cell vitality and proliferation. Further benefits may be realized by using numerous micro-robots together in bioprinting, the creation of a design that can be utilized by a bioprinter to generate tissue and other complex materials in the laboratory environment.
Khademhosseini lab publications partial list. Just the 2014 articles year to date
1. N. Kaushik, P. Sharma, S. Ahadian, A. Khademhosseini, M. Takahashi, A. Makino, S. Tanaka, and M. Esashi, Metallic glass thin films for potential biomedical applications, J Biomed Mater Res B Appl Biomater (2014) (Journal article)
2. H. Bae, H. Chu, F. Edalat, J.M. Cha, S. Sant, A. Kashyap, A.F. Ahari, C.H. Kwon, J. W. Nichol, S. Manoucheri, B. Zamanian, Y. Wang, A. Khademhosseini Development of functional biomaterials with micro‐and nanoscale technologies for tissue engineering and drug delivery applications, Journal of tissue engineering and regenerative medicine, 2014, 8 (1), 1-14 (Journal article)
3. H.Y. Hsieh, G. Camci-Unal, T.W. Huang, R. Liao, T.J. Chen, A. Paul, F.G. Tseng, A. Khademhosseini Gradient static-strain stimulation in a microfluidic chip for 3D cellular alignment, Lab on a Chip, 2014, 14 (3), 482-493 (Journal article)
4. M. Ochoa, R. Rahimi, H.L. Tiffany, A. Neslihan; A. Khademhosseini, M. Dokmeci, B. Ziaie A paper-based oxygen generating platform with spatially defined catalytic regions, Sensors and Actuators B: Chemical (2014) (Journal article)
5. A. Hasan, A. Memic, N. Annabi, M. Hossain, A. Paul, M. R. Dokmeci, F. Dehghani & A. Khademhosseini Electrospun scaffolds for tissue engineering of vascular grafts, Acta Biomater 10, 11-25 (2014) (Journal article)
6. A. Polini, L. Prodanov, N. S. Bhise, V. Manoharan, M. R. Dokmeci, A. Khademhosseini Organs-on-a-chip: a new tool for drug discovery, Expert Opin. Drug Discov., 2014, 9-4,335–52 (Journal article)
7. N. Annabi, A. Tamayol, J.A. Uquillas, M. Akbari, L.E. Bertassoni, C. Cha, G. Camci‐Unal, M.R. Dokmeci, N. A Peppas, A. Khademhosseini 25th anniversary article: Rational design and applications of hydrogels in regenerative medicine, Advanced Materials, 2014, 26 (1), 85-124 (Journal article)
8. R. Obregon, J. Ramon-Azcon, S. Ahadian, H. Shiku, M. Ramalingam, A. Khademhosseini, T. Matsue “Gradient biomaterials as tissue scaffolds” in “Stem Cell Biology and Tissue Engineering in Dental Sciences”, Editors: Ajaykumar Vishwakarma, Paul Sharpe, Songtao Shi, Xiu-Ping Wang, Murugan Ramalingam, Elsevier. (2014) In press. (Book chapter)
9. N. Masoumi, B. L. Larson, N. Annabi, M. Kharaziha, B. Zamanian, K. S. Shapero, A.T. Cubberley, G. Camci-Unal, K. B. Manning, J. E. Mayer, A. Khademhosseini Electrospun PGS:PCL microfibers align human valvular interstitial cells and provide tunable scaffold anisotropy, Adv Healthc Mater (2014) (Journal article)
10. Y. Shevchenko, G. Camci-Unal, D.F. Cuttica, M.R. Dokmeci, J. Alberta, A. Khademhosseini Surface plasmon resonance fiber sensor for real-time and label-free monitoring of cellular behavior, Biosens Bioelectron 56, 359-367 (2014) (Journal article)
11. Gaharwar, Akhilesh K.; Mihaila, Silvia M.; Kulkarni, Ashish A.; Patel, Alpesh; Di Luca, Andrea; Reis, Rui L.; Gomes, Manuela E.; van Blitterswijk, Clemens; Moroni, Lorenzo; Khademhosseini, Ali Amphiphilic Beads as Depots for Sustained Drug Release Integrated into Fibrillar Scaffolds (Journal article)
12. M. Akbari, A. Tamayol, N. Annabi, D. Juncker, A. Khademhosseini “Microtechnologies in the fabrication of fibers for tissue engineering” in “Microfluidics for medicine or medical applications”, edited by A. van der Berg and L. Segerink. Royal Society of Chemistry (2014) In press (Book chapter)
13. S. Ostrovidov, X. Shi, L. Zhang, X. Liang, S.B. Kim, T. Fujie, M. Ramalingam, M. Chen, K. Nakajima, F. Al-Hazmi, H. Bae, A. Memic, A. Khademhosseini Myotube formation on gelatin nanofibers–Multi-walled carbon nanotubes hybrid scaffolds, Biomaterials, 2014, 35, 24, 6268–6277 (Journal article)
14. X. Zhao, Š. Selimović, G. Camci-Unal, M. R. Dokmeci, L. Yildirimer, N. Annabi, A. Khademhosseini “Microfabrication of three-dimensional vascular structures” in “Vascularization: Regenerative Medicine and Tissue Engineering”, Editor: Eric Brey, CRC Press. (2014). ISBN 9781466580459 (Book chapter)
15. S. Ahadian, S. Ostrovidov, T. Fujie, P. P. Selvakumar, H. Kaji, K. Sampathkumar, M. Ramalingam, A. Khademhosseini “Microfabrication and nanofabrication techniques for dental tissue engineering and regeneration” in “Stem Cell Biology and Tissue Engineering in Dental Sciences” edited by Ajaykumar Vishwakarma, Paul Sharpe, Songtao Shi, Xiu-Ping Wang, Murugan Ramalingam, Elsevier. (2014) In press. (Book chapter)
16. S. Ostrovidov, A. Seidi, K. Sampathkumar, A. Srivastava, A. Khademhosseini, M. Ramalingam “Introduction to nanobioscience: A tissue engineering perspective”. In the Encyclopedia of Live Support Systems (EOLSS), UNESCO, (Ch. 6.152.34) (2014) (Book chapter)
17. T. Fujie, S. Ostrovidov, S., Ahadian, S. Prakash Parthiban, A. Khademhosseini, H., Kaji. “Muscle biology and structure for use in bioengineered muscle tissue devices” in “Handbook of Biomimetics and Bioinspiration” 3 Volume Set. Editors: E. Jabbari, A. Khademhosseini, L.P. Lee, D.-H. Kim, A. Ghaemmaghami. World Scientific Publishing, Singapore (2014). ISBN: 978-981-4354-92-9 (Book chapter)
18. T. Fujie, Y. Mori, S. Ito, M. Nishizawa, H. Bae, N. Nagai, H. Onami, T. Abe, A. Khademhosseini, H. Kaji Micropatterned polymeric nanosheets for local delivery of an engineered epithelial monolayer, Adv Mater 26, 1699-1705 (2014) (Journal article)
19. C. Cha, P. Soman, W. Zhu, M. Nikkhah, G. Camci-Unal, S. Chen, A. Khademhosseini Structural reinforcement of cell-laden hydrogels with microfabricated three dimensional scaffolds, Biomaterials Science, Biomaterials Science 2, 703-709 (2014) (Journal article)
20. S. Rajabi-Zeleti, S.J. Firoozinezhad, M. Azarnia, F. Khayyatan, S. Vahdat, S. Nikeghbalian, A. Khademhosseini, H. Baharvand, N. Aghdami The behavior of cardiac progenitor cells on macroporous pericardium-derived scaffolds, Biomaterials 35 (3), 970-982. (Journal article)
21. J. Almodovar, R. Guillot, C. Monge, J. Vollaire, S. Selimovic, J. L. Coll, A. Khademhosseini & C. Picart Spatial patterning of bmp-2 and bmp-7 on biopolymeric films and the guidance of muscle cell fate, Biomaterials 35, 3975-3985 (2014) (Journal article)
22. A.K. Gaharwar, N.A. Peppas, A. Khademhosseini Nanocomposite hydrogels for biomedical applications, Biotechnol Bioeng 111, 441-453 (2014) (Journal article)
23. S. Ostrovidov, V. Hosseini, T. Fujie1, S.P. Parthiban, S. Ahadian, M. Ramalingam, H. Bae, H. Kaji, A. Khademhosseini Skeletal muscle tissue engineering: Methods to form skeletal myotubes and their applications, Tissue Eng Part B Rev (2014) (Journal article)
24. L.E. Bertassoni, J.C. Cardoso, V. Manoharan, A.L. Cristino, N.S. Bhise, W.A. Araujo, P. Zorlutuna, N.E. Vrana, A.M. Ghaemmaghami, M.R. Dokmeci, A. Khademhosseini Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels, Biofabrication 6, 024105 (2014) (Journal article)
25. C. Cha, J. Oh, K. Kim, Y. Qiu, M. Joh, S.R. Shin, X. Wang, G. Camci-Unal, K. Wan, R. Liao, A. Khademhosseini Microfluidics-assisted fabrication of gelatin-silica core-shell microgels for injectable tissue constructs, Biomacromolecules 15, 283-290 (2014) (Journal article)
26. X. Shi, S. Ostrovidov, Y. Shu, X. Liang, K. Nakajima, H. Wu, A. Khademhosseini Microfluidic generation of polydopamine gradients on hydrophobic surfaces, Langmuir 30, 832-838 (2014) (Journal article)
27. S. Ahadian, J. Ramón-Azcón, M. Estili, X. Liang, S. Ostrovidov, H. Shiku, M. Ramalingam, K. Nakajima, Y. Sakka, H. Bae, T. Matsue, A. Khademhosseini Hybrid hydrogels containing vertically aligned carbon nanotubes with anisotropic electrical conductivity for muscle myofiber fabrication, Sci Rep 4, 4271 (2014) (Journal article)
28. A.K. Gaharwar, S. Mukundan, E. Karaca, A.Dolatshahi-Pirouz, A. Patel, K. Rangarajan, S.M. Mihaila, G. Iviglia, H. Zhang, A. Khademhosseini nanoclay enriched poly(ε-caprolactone) electrospun scaffolds for osteogenic differentiation of human mesenchymal stem cells, Tissue Engineering Part A (2014) (Journal article)
29. S. Naahidi, M. Jafari, M. Logan, F. Edalat, A. Khademhosseini, B. Dixon & P. Chen Immuno- and hemocompatibility of amino acid pairing peptides for potential use in anticancer drug delivery, Journal of Bioactive and Compatible Polymers: Biomedical Applications (2014) (Journal article)
30. M. Akbari, A. Tamayol, V. Laforte, N. Annabi, A. H. Najafabadi, A. Khademhosseini, D. Juncker, “ Composite Living Fibers for Creating Tissue Constructs Using Textile Techniques, Adv. Funct. Mater., 2014 (Journal article)
31. S. K. Ameri, P. K. Singh, M. R. Dokmeci, A. Khademhosseini, Q. Xu & S. R. Sonkusale All electronic approach for high-throughput cell trapping and lysis with electrical impedance monitoring, Biosens Bioelectron 54, 462-467 (2014) (Journal article)
32. C. Cha, S. R. Shin, X. Gao, N. Annabi, M. R. Dokmeci, X. S. Tang & A. Khademhosseini Controlling mechanical properties of cell-laden hydrogels by covalent incorporation of graphene oxide, Small 10, 514-523 (2014) (Journal article)
33. A. Dolatshahi-Pirouz, M. Nikkhah, A. K. Gaharwar, B. Hashmi, E. Guermani, H. Aliabadi, G. Camci-Unal, T. Ferrante, M. Foss, D. E. Ingber & A. Khademhosseini A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells, Sci Rep 4, 3896 (2014) (Journal article)
34. E. Jabbari, D.-H. Kim, L. P. Lee, A. Ghaemmaghami & A. Khademhosseini “Handbook of Biomimetics and Bioinspiration: Biologically-Driven Engineering of Materials, Processes, Devices, and Systems” World Scientific Series in Nanoscience and Nanotechnology. (2014) ISBN: 978-981-4354-92-9 (Journal article)
35. X. Shi, T. Fujie, A. Saito, S. Takeoka, Y. Hou, Y. Shu, M. Chen, H. Wu & A. Khademhosseini Periosteum-mimetic structures made from freestanding microgrooved nanosheets, Adv Mater (2014) (Journal article)
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