Bioprinted gelatin hydrogel platform promotes smooth muscle cell contractile phenotype maintenance
- 244 Downloads
Three dimensional (3D) bioprinting has been proposed as a method for fabricating tissue engineered small diameter vascular prostheses. This technique not only involves constructing the structural features to obtain a desired pattern but the morphology of the pattern may also be used to influence the behavior of seeded cells. Herein, we 3D bioprinted a gelatin hydrogel microchannel construct to promote and preserve the contractile phenotype of vascular smooth muscle cells (vSMCs), which is crucial for vasoresponsiveness. The microchanneled surface of a gelatin hydrogel facilitated vSMC attachment and an elongated alignment along the microchannel direction. The cells displayed distinct F-actin anisotropy in the direction of the channel. The vSMC contractile phenotype was confirmed by the positive detection of contractile marker gene proteins (α-smooth muscle actin (α-SMA) and smooth muscle-myosin heavy chain (SM-MHC)). Having demonstrated the effectiveness of the hydrogel channels bioprinted on a film, the bioprinting was applied radially to the surface of a 3D tubular construct by integrating a rotating mandrel into the 3D bioprinter. The hydrogel microchannels printed on the 3D tubular vascular construct also orientated the vSMCs and strongly promoted the contractile phenotype. Together, our study demonstrated that microchannels bioprinted using a transglutaminase crosslinked gelatin hydrogel, could successfully promote and preserve vSMC contractile phenotype. Furthermore, the hydrogel bioink could be retained on the surface of a rotating polymer tube to print radial cell guiding channels onto a vascular graft construct.
Keywords3D extrusion bioprinting Gelatin hydrogel Transglutaminase Vascular prosthesis Vascular smooth muscle cells Contractile phenotype
This research is supported by the Singapore National Research Foundation under CREATE programme (NRF-Technion): The Regenerative Medicine Initiative in Cardiac Restoration Therapy Research Program.
Compliance with ethical standards
Statement of ethical approval
No ethical approval was required for this study.
Conflict of interest
The authors declare no conflict of interests.
- G. Abagnale, M. Steger, V.H. Nguyen, N. Hersch, A. Sechi, S. Joussen, B. Denecke, R. Merkel, B. Hoffmann, A. Dreser, U. Schnakenberg, A. Gillner, W. Wagner, Surface topography enhances differentiation of mesenchymal stem cells towards osteogenic and adipogenic lineages. Biomaterials 61, 316–326 (2015)CrossRefGoogle Scholar
- A. Agrawal, B.H. Lee, S.A. Irvine, J. An, R. Bhuthalingam, V. Singh, K.Y. Low, C.K. Chua, S.S. Venkatraman, Smooth muscle cell alignment and phenotype control by melt spun Polycaprolactone fibers for seeding of tissue engineered blood vessels. Int. J. Biomater. 434876 (2015)Google Scholar
- R. Bhuthalingam, P.Q. Lim, S.A. Irvine, and S.S. Venkatraman, Automated Robotic Dispensing Technique for Surface Guidance and Bioprinting of Cells, J. Vis. Exp. 117, e54604 (2016)Google Scholar
- G. Cama, D.E. Mogosanu, A. Houben and P. Dubruel, Synthetic biodegradable medical polyesters: Poly-ε-caprolactone. In Xiang Zhang (Ed.), Science and Principles of Biodegradable and Bioresorbable Medical Polymers ( Woodhead Publishing, 2017)Google Scholar
- C.Y. Tay, Y-L. Wu, P. Cai, N.S. Tan, S.S Venkatraman, X. Chen, L.P Tan, Bio-inspired micropatterned hydrogel to direct and deconstruct hierarchical processing of geometry-force signals by human mesenchymal stem cells during smooth muscle cell differentiation. NPG Asia Materials 7, e199 (2015)Google Scholar
- T.K. Merceron, S.V. Murphy, in Anthony Atala and James J. Yoo (Eds.), Essentials of 3D Biofabrication and Translation. Hydrogels for 3D Bioprinting applications (Academic Press, Boston, 2015)Google Scholar
- H. Omidian, K. Park, Introduction to hydrogels. in, Biomedical applications of hydrogels handbook (Springer, 2010)Google Scholar
- S. Pashneh-Tala, S. MacNeil, F. Claeyssens, The Tissue-Engineered Vascular Graft-Past, Present, and Future (B Rev, Tissue Eng Part, 2015)Google Scholar
- F. Pati, J. Jang, W.L. J.W. Lee, D.W. Cho, Extrusion Bioprinting. In Anthony Atala and James J. Yoo (Eds.), Essentials of 3D Biofabrication and Translation (Academic Press, 2015)Google Scholar
- J. Puetz, M. A. Aegerter, Dip Coating Technique. in Michel A. Aegerter and Martin Mennig (eds.), Sol-Gel Technologies for Glass Producers and Users (Springer US: Boston, MA, 2004)Google Scholar
- J.A.G. Rhodin, Architecture of the Vessel Wall. In, Comprehensive Physiology (John Wiley & Sons, Inc., 2011)Google Scholar
- A. Tijore, S. A. Irvine, U. Sarig, P. Mhaisalkar, V. Baisane, S. S. Venkatraman, Contact Guidance for Cardiac Tissue Engineering Using 3D Bioprinted Gelatin Patterned hydrogel, Biofabrication 10(2):025003 (2017)Google Scholar
- S.K. Yazdani, B. Watts, M. Machingal, Y.P. Jarajapu, M.E. Van Dyke, G.J. Christ, Smooth muscle cell seeding of decellularized scaffolds: The importance of bioreactor preconditioning to development of a more native architecture for tissue-engineered blood vessels. Tissue Eng. Part A 15, 827–840 (2009)CrossRefGoogle Scholar