A collagen-poly(lactic acid-co-3-caprolactone) hybrid scaffold for bladder tissue regeneration Eva-Maria Engelhardt a , Lionel A. Micol a , Stephanie Houis b , Florian M. Wurm c , Jöns Hilborn d , Jeffrey A. Hubbell a , Peter Frey a, e, * a Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Laboratory for Experimental Pediatric Urology and Regenerative Medicine & Pharmacobiology, CH-1015 Lausanne, Switzerland b Institut für Textiltechnik, RWTH Aachen University, D-52062 Aachen, Germany c Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Laboratory of Cellular Biotechnology, CH-1015 Lausanne, Switzerland d Polymer Chemistry, Angström Laboratory, Uppsala University, SE-75121 Uppsala, Sweden e Centre Hospitalier Universitaire Vaudois, Department of Pediatric Urology, CH-1011 Lausanne, Switzerland article info Article history: Received 29 November 2010 Accepted 9 February 2011 Available online 4 March 2011 Keywords: Bladder tissue engineering Scaffold Collagen Copolymer In vitro test In vivo test abstract Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagenepoly(lactic acid-co-3-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagenePLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. CollagenePLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Congenital anomalies and diseases of the bladder, such as interstitial cystitis, acquired neurogenic bladder, or bladder cancer, may require reconstructive surgery. The standard surgical treat- ment involves the use of vascularized intestinal tissue to augment or replace the diseased bladder. The application of intestinal segments within the urinary tract may generate complications, such as metabolic disturbances, increased mucus production, stone formation, chronic infection, and even malignancy. Therefore, there is a strong need for alternative bladder tissue substitutes in the clinic [1]. Collagen-based scaffolds have proven to be adequate scaffolds for human bladder cells [2e4]. Manufactured collagen-based scaf- folds exist in forms of gels and chemically crosslinked sponges. Gels have the disadvantage of being mechanically weak, but allow a homogenous, three-dimensional cell distribution throughout the scaffold upon seeding. In contrast, sponges are stronger, but due to their chemical modification they are less biomimetic and less prone to remodeling by cells [5]. Furthermore, only surface seeding can be performed. A successful strategy to enhance mechanical properties of cellular and acellular collagen gels without chemical modifica- tion is plastic compression (pc), a technique developed by Brown et al. [5]. However, pc collagen gels are still too weak to be sutured and conveniently handled in clinical use. We sought to explore further enhancement of the strength of pc collagen gels by integration of a biodegradable synthetic co-poly- mer mesh within the collagen gel. This hybrid scaffold overcomes the weak points of pc collagen gels mentioned above while * Corresponding author. EPFL-SV-IBI-LMRP, Pediatric Surgery, Station 15, CH-1015 Lausanne, Switzerland. Tel.: þ41 21 693 96 62; fax: þ41 21 314 31 01. E-mail address: peter.frey@epfl.ch (P. Frey). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2011.02.012 Biomaterials 32 (2011) 3969e3976