A Polyurethane-Gelatin Hybrid Construct for Manufacturing Implantable Bioartificial Livers

Abstract

A novel 3D hybrid construct was developed for liver manufacturing by depositing biodegradable polyurethane (PU) and a naturally derived polymer gelatin simultaneously via a double nozzle rapid prototyping (RP) technique. A grid object was produced by precisely and simultaneously dispersing the PU and gelatin to form 3D constructs with interconnected macro-channels at a low temperature (-28°C). Micro-pores were formed by freeze-drying the constructs. The PU polymer provided mechanical support while gelatin provided accommodation for implant cells. The hydrophilicity of the hybrid constructs was between the pure PU and pure gelatin structures. The interconnected channels allow nutrients and oxygen to be supplied throughout the construct as well as provide space for the attachment of cells. The design and fabrication strategies, used to create complex physical objects directly from computer aided design (CAD) models, represent a promising technique for implantable bioartificial livers. It is anticipated that these PU-gelatin hybrid constructs will serve as a useful model for bioartificial liver manufacturing.

Keywords

rapid prototyping (RP)hybrid construct vascular systems cell assembling liver manufacturing.

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References

Zdrahala, R.J. and Zdrahala, I.J. (1999). Biomedical Applications of Polyurethanes: A Review of Past Promises, Present Realities, and a Vibrant Future , Journal of Biomaterials Applications, 14(1): 67-90.

Wang, X.H. , Yan, Y.N. and Zhang, R.J. (2007). Rapid Prototyping as a Tool for Manufacturing Bioartificial Livers . Trends in Biotechnology, 25(11): 505-513.

Ciardilli, G. , Rechichi, A. , Sartori, S. , D'Acunto, M. , Caporale, A. , Peggion, E. , et al. (2006). Bioactive Polyurethanes in Clinical Applications , Polymers for Advanced Technologies , 17: 786-789.

Xu, W. , Wang, X.H. , Yan, Y.N. and Zhang, R.J. (2008). Rapid Prototyping of Polyurethane for the Creation of Branched Vascular Systems , J. Bioact. Comp. Polym., 23(2): 154-170 (Featured by Nature China on May 3, 2008).

Yan, Y.N. , Wang, X.H. , Yin, D.Z. and Zhang, R.J. (2007). A New Polyurethane/Heparin Vascular Graft for Small-caliber Vein Repair , J. Bioact. Compat. Polym., 22(3): 323-341.

Ciardelli, G. , Rechichi, A. , Cerrai, P. , Tricoli, M. , Barban, N. and Giusti, P. (2004). Segmented Polyurethanes for Medical Applications: Synthesis, Characterization and In Vitro Enzymatic Degradation Studies , Macromolecular Symposia , 218(1): 261-271.

Yan, Y.N. , Wang, X.H. , Xiong, Z. , Liu, H.X. , Liu, F. , Lin, F. et al. (2005). Direct Construction of a Three-dimensional Structure with Cells and Hydrogel , J. Bioact. Compat. Polym., 20: 259-269.

Wang, X.H. , Yan, Y.N. , Pan, Y.Q. , Xiong, Z. , Liu, H.X. , Cheng, J. et al. (2006). Generation of Three-dimensional Hepatocyte/gelatin Structures with Rapid Prototyping System , Tissue Engineering , 12(1): 83-90.

Yan, Y.N. , Wang, X.H. , Pan, Y.Q. , Liu, H.X. , Cheng, J. , Xiong, Z. et al. (2005). Fabrication of Viable Tissue-engineered Constructs with 3D Cell-assembly Technique , Biomaterials, 26: 5864-5871.

10.

Xu, W. , Wang, X.H. , Yan, Y.N. , Zheng, W. , Xiong, Z. , Lin, F. et al. (2007). Rapid Prototyping of Three-dimensional Cell/Gelatin/Fibrinogen Constructs for Medical Regeneration , J. Bioact. Compat. Polym., 22(4): 363-377.

11.

Hiraoka, Y. , Kimura, Y. , Ueda, H. and Tabata, Y. (2003). Fabrication and Biocompatibility of Collagen Sponge Reinforced with Poly(Glycolic Acid) Fiber , Tissue Engineering, 9: 1101-1112.

12.

Chen, G.P. , Ushida, T. and Tateishi, T. (2001). Poly(DL-lactic-co-glycolic acid) Sponge Hybridized with Collagen Microsponges and Deposited Apatite Particulates , Journal of Biomedical Materials Research, 57: 8-14.

13.

Matsumoto, K. , Ohnishi, K. , Kiyotani, T. , Sekine, T. , Ueda, H. , Nakamura, T. et al. (2000). Peripheral Nerve Regeneration across an 80-mm Gap Bridged by a Polyglycolic Acid (PGA)-collagen Tube Filled with Laminin-coated Collagen Fibers: A Histological and Electrophysiological Evaluation of Regenerated Nerves , Brain Research, 869: 315-320.

14.

Yeong, W.Y. , Chua, C.K. , Leong, K.F. and Chandrasekaran, M. (2004). Rapid Prototyping in Tissue Engineering: Challenges and Potential , Trends in Biotechnology , 22: 643-652.

15.

Khalil, S. , Nam, F. and Sun, W. (2005). Multi-nozzle Deposition for Construction of 3D Biopolymer Tissue Scaffolds , Rapid Prototyping Journal, 11: 9-17.

16.

Liu, L. i., Yan, Y.N. , Xiong, Z. , Zhang, R.J. and Wang, X.H. A Novel poly(lactic-co-glycolic acid)-collagen Hybrid Scaffold Fabricated via Multi-nozzle Low-temperature Deposition . The 3rd International Conference on Advanced Research in Virtual and Rapid Prototyping . Virtual Rapid Manufacturing? Bártolo et al. (eds). © 2008 Taylor & Francis Group, London, ISBN 978-0-415-41602-3. (VRAP, www.dem.estg. ipleiria.pt/vrap 2007)

17.

Yin, D.Z. , Wang, X.H. , Yan, Y.N. and Zhang, R.J. (2007). Preliminary Studies on Peripheral Nerve Regeneration along a New Polyurethane Conduit , J. Bioact. and Compat. Polym., 22(2): 143-159.