Engineering functional bladder tissues Maya Horst 1 , Srinivas Madduri 1 , Rita Gobet 3 , Tullio Sulser 1 , Vinzent Milleret 2 , Heike Hall 2 , Anthony Atala 4 and Daniel Eberli 1 * 1 Laboratory for Urologic Tissue Engineering and Stem Cell Therapy, Department of Urology, University Hospital, Zurich, Switzerland 2 Cells and Biomaterials, Department of Materials, ETH Zurich, Switzerland 3 Division of Pediatric Urology, Department of Pediatric Surgery, University Children’s Hospital, Zurich, Switzerland 4 Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA Abstract Purpose: End stage bladder disease can seriously affect patient quality of life and often requires surgical reconstruction with bowel tissue, which is associated with numerous complications. Bioengineering of functional bladder tissue using tissue-engineering techniques could provide new functional tissues for reconstruction. In this review, we discuss the current state of this field and address different approaches to enable physiologic voiding in engineered bladder tissues in the near future. Materials and Methods: In a collaborative effort, we gathered researchers from four institutions to discuss the current state of functional bladder engineering. A MEDLINE W and PubMed W search was conducted for articles related to tissue engineering of the bladder, with special focus on the cells and biomaterials employed as well as the microenvironment, vascu- larisation and innervation strategies used. Results: Over the last decade, advances in tissue engineering technol- ogy have laid the groundwork for the development of a biological substitute for bladder tissue that can support storage of urine and restore physiologic voiding. Although many researchers have been able to demonstrate the formation of engineered tissue with a structure similar to that of native bladder tissue, restoration of physiologic voiding using these constructs has never been demonstrated. The main issues hindering the development of larger contractile tissues that allow physiologic voiding include the development of correct muscle alignment, proper innervation and vascularization. Conclusion: Tissue engineering of a construct that will support the contractile properties that allow physiologic voiding is a complex process. The combination of smart scaffolds with controlled topography, the ability to deliver multiple trophic factors and an optimal cell source will allow for the engineering of functional bladder tissues in the near future. Copyright © 2012 John Wiley & Sons, Ltd. Received 11 May 2011; Revised 12 September 2011; Accepted 14 November 2011 Keywords bioengineering; functional bladder tissue; scaffolds; innervation; vascularization 1. Introduction Replacement of the urinary bladder in whole or part is indicated in a variety of clinical disorders. After radical cystectomy in patients with invasive bladder cancer, the entire bladder is substituted. In patients with anatomical or func- tional bladder outlet obstruction including congenital anoma- lies, benign prostatic hypertrophy and neuropathic bladder secondary to spina bifida or spinal cord injury, partial bladder replacement (bladder enlargement) is performed. Currently, intestinal tissue is used to replace or reconstruct the urinary bladder. However, the use of intestinal tissue is associated with numerous complications such as metabolic disturbance, increased mucus production, urolithiasis, infections and even malignancy. Over the last decade, a better understanding of the biology and physiology of the urinary tract as well as advances in tissue engineering (TE) technology have laid the groundwork for the development of biological substitutes for native organs. For hollow organs such as the bladder, urethra, oesophagus, intestine, vagina, or blood vessels, TE strategies generally include implantation of a scaffold that is either unseeded or pre-seeded with cultured cells. Most often, to create cell-seeded scaffolds, autologous cells are dissociated from a tissue biopsy, expanded in culture and seeded onto a biomaterial in vitro. The construct is then allowed to mature in a bioreactor for a short time before it is implanted into the patient. After implantation, the scaffold becomes *Correspondence to: Daniel Eberli, University Hospital Zurich, Frauenklinikstr. 10, CH-8091 Zurich, Switzerland. E-mail: daniel. eberli@usz.ch Copyright © 2012 John Wiley & Sons, Ltd. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE REVIEW J Tissue Eng Regen Med (2012) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.547