Regenerative medicine, tissue engineering and biomedical research give hope to many patients who need bio-implants. Tissue engineering applications have already been developed based on bioreactors. Physiological ureter implants, however, do not still function sufficiently, as they represent tubular hollow structures with very specific cellular structures and alignments consisting of several cell types. The aim of this study was to a develop a new bioreactor system based on seamless, collagenous, tubular OPTIMAIX 3D prototype sponge as scaffold material for ex-vivo culturing of a tissue engineered ureter replacement for future urological applications. Particular emphasis was given to a great extent to mimic the physiological environment similar to the in vivo situation of a ureter. NIH-3T3 fibroblasts, C2C12, Urotsa and primary genitourinary tract cells were applied as co-cultures on the scaffold and the penetration of cells into the collagenous material was followed. By the end of this study, the bioreactor was functioning, physiological parameter as temperature and pH and the newly developed BIOREACTOR system is applicable to tubular scaffold materials with different lengths and diameters. The automatized incubation system worked reliably. The tubular OPTIMAIX 3D sponge was a suitable scaffold material for tissue engineering purposes and co-cultivation procedures.

Keywords:
Tissue engineering, Automatized bioreactor, Tubular scaffold, Biohybrid, Collagen, Ureter replacement, Urethra replacement, Primary cell culture
1.
Tschoeke B, Flanagan TC, Koch S, Harwoko MS, Deichmann T, Ellä V, et al: Tissue-Engineered Small-Caliber Vascular Graft based on a novel biodegradable composite fibrin-polylactide scaffold. Tissue Eng Part A 2009;15:1909-1918.
2.
Seliktar D, Black RA, Vito RP, Nerem RM: Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro. Ann Biomed Eng 2000;28:351-362.
3.
Liu M, Liu N, Zang R, Li Y, Yang ST: Engineering stem cell niches in bioreactors. World J Stem Cells 2013;5:124-135.
4.
Davis NF, Mooney R, Piterina AV, Callanan A, McGuire BB, Flood HD, et al: Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes. Urology 2011;78:954-960.
5.
Mills I, Cohen CR, Kamal K, Li G, Shin T, Du W, et al: Strain activation of bovine aortic smooth muscle cell proliferation and alignment: study of strain dependency and the role of protein kinase A and C signaling pathways. J Cell Physiol 1997;170:228-234.
6.
Guldberg RE, Awad HA, Vunjak-Novakovic G, Donahue H, Das A: Principles of engineering tissue regeneration (Sun Valley 2012). IBMS Bonekey 2013;10:13-14.
7.
Skalak R, Fox CF: Tissue Engineering; in Skalak R, Fox CF (eds): Tissue Engineering, Proceedings of a Workshop, held at Granibakken. Alan R. Liss Inc., New York, 1988.
8.
Martin I, Wendt D, Heberer M: The role of bioreactors in tissue engineering. Trends Biotechnol 2004;22:80-86.
9.
Instructions for Use - Optimaix-3D™ scaffolds. 2010.
10.
Freed LE, Vunjak-Novakovic G: Microgravity tissue engineering. In Vitro Cell Dev Biol Anim 1997;33:381-385.
11.
Sodian R, Lemke T, et al: Tissue-engineering bioreactors: a new combined cell-seeding and perfusion system for vascular tissue engineering. Tissue Eng 2002;8:863-870.
12.
Murphy SV, Atala A: Organ engineering - combining stem cells, biomaterials, and bioreactors to produce bioengineered organs for transplantation. Bioessays 2013;35:163-172.
13.
Gu GL, Xia SJ, Zhang J, Liu GH, Yan L, Xu ZH, et al: Tubularized urethral replacement using tissue-engineered peritoneum-like tissue in a rabbit model. Urol Int 2012;89:358-364.
14.
Balsara ZR, Ross SS, Dolber PC, Wiener JS, Tang Y, Seed PC: Enhanced susceptibility to urinary tract infection in the spinal cord-injured host with neurogenic bladder. Infect Immun 2013;81:3018-3026.
15.
Brehmer B, Rohrmann D, Becker C, Rau G, Jakse G: Different types of scaffolds for reconstruction of the urinary tract by tissue engineering. Urol Int 2007;78:23-29.
16.
Brehmer B, Rohrmann D, Rau G, Jakse G: Bladder wall replacement by tissue engineering and autologous keratinocytes in minipigs. BJU Int 2006;97:829-836.
17.
Becker C, Olde Damink L, Laeufer T, Brehmer B, Heschel I, Jakse G: ‘UroMaix' scaffolds: novel collagen matrices for application in tissue engineering of the urinary tract. Int J Artif Organs 2006;29:764-771.
18.
Montzka K, Läufer T, Becker C, Grosse J, Heidenreich A: Microstructure and cytocompatibility of collagen matrices for urological tissue engineering. BJU Int 2011;107:1974-1981.
19.
Leonhäuser D, Seifarth V, Strick K, Gaisa N, Heschel I, Tolba RH, et al: 871 Bladder wall substitution with autologously seeded collagen scaffolds ‘Optimaix' in a Göttingen minipig model. Eur Urol Suppl 2013;12:e871.
20.
Leonhäuser D, Strick K, Seifarth V, Huppertz N, Fera C, Gaisa N, et al: Vergleich zweier biodegradierbarer Kollagenscaffolds ‘OPTIMAIX' als möglicher Blasenwandersatz im Göttinger Minipig Modell; in Kongress der Deutschen Gesellschaft für Urologie e.V. Dresden, 2013, p 96.
21.
El-Assmy A, Hafez AT, El-Sherbiny MT, El-Hamid MA, Mohsen T, Nour EM, et al: Use of single layer small intestinal submucosa for long segment ureteral replacement: a pilot study. J Urol 2004;171:1939-1942.
22.
El-Hakim A, Marcovich R, Chiu KY, Lee BR, Smith AD: First prize: ureteral segmental replacement revisited. J Endourol 2005;19:1069-1074.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.