REGULAR ARTICLE A collagen-based interface construct for the assessment of cell-dependent mechanical integration of tissue surfaces M. Marenzana & D. J. Kelly & P. J. Prendergast & R. A. Brown Received: 8 March 2006 / Accepted: 1 August 2006 / Published online: 6 October 2006 # Springer-Verlag 2006 Abstract The interface between any newly engineered tissue and pre-existing tissue is of great importance to tissue engineering; however, this process has so far been largely ignored, with few reports regarding the mechanical strength of newly integrated connective tissues surfaces. A new model system has been developed to generate a well- defined interface between two collagen lattices: one pre- contracted by resident fibroblasts and the other a cell-free wrapping gel. This construct can be cultured for prolonged periods (>2 weeks) and can also be fitted onto a mechanical testing system to measure the interface adhesive strength at the end of the culture time. Interface adhesive strength shows a six-fold increase after 1 week in culture, compared with the time-zero baseline. Observations of cell migration across the interface suggest that cell translocation in the three-dimen- sional matrix might play an important role in the integration process. In this new controlled geometry, normal and shear stresses at the interface can be analysed by finite element modelling and the areas at which debonding starts can be defined. The current experimental design permits solid mul- tiple (homogeneous or heterogeneous) interface formation in vitro with a well-defined geometry and the possibility of measuring mechanical linkage. This design should enable many other factors affecting cell-driven interface strength- ening to be investigated. Keywords Engineered tissue interface . Tissue integration in vitro . Cell migration . Three-dimensional matrix . Finite element analysis . Tissue interfaces . Collagen gel . Rat Introduction Concepts in tissue engineering have focused mainly on the production of a variety of tissues or even organs. These have included such diverse structures as skin, cornea, artery, nerve, cartilage, bone, bladder and liver and, in most cases, model systems have been developed for the three-dimen- sional (3D) support and culture of cell populations on a biodegradable support matrix (Brown 2000). Support matrices in use are either derived from aggregates of natural macromolecules (collagen, fibrin, fibronectin, hy- aluronan, soya protein) or synthetic polymers (e.g. poly- lactic acid, glycolic acid, capriolactone). However, the vast majority of work has clearly concen- trated on engineering single tissues, i.e. relatively homoge- neous entities. This current approach offers little within an area of major importance in surgical tissue reconstruction and repair biology, namely the engineering of tissue interfaces. Interfaces between tissues (particularly if adjacent tissues are injured or diseased) represent a major clinical difficulty, although techniques allowing intervention at this level would offer many new avenues for effective reconstruction Cell Tissue Res (2007) 327:293–300 DOI 10.1007/s00441-006-0316-z This study was supported by the Fifth Framework Programme of the European Commission, “Biomechanical Interactions in Tissue Engineering and Surgical Repair (BITES)”. M. Marenzana : R. A. Brown (*) RFUCMS, Tissue Repair and Engineering Centre, Institute of Orthopaedics, Stanmore Campus, University College London, Brockley Hill, Stanmore HA7 4LP, UK e-mail: rehkrab@ucl.ac.uk D. J. Kelly : P. J. Prendergast Bioengineering Group, Department of Mechanical and Manufacturing Engineering, Parsons Building, Trinity College Dublin, Dublin 2, Ireland