title: In vivo screening of extracellular matrix components produced under multiple experimental conditions implanted in one animal.
abstract: Animal experiments help to progress and ensure safety of an increasing number of novel therapies, drug development and chemicals. Unfortunately, these also lead to major ethical concerns, costs and limited experimental capacity. We foresee a coercion of all these issues by implantation of well systems directly into vertebrate animals. Here, we used rapid prototyping to create wells with biomaterials to create a three-dimensional (3D) well-system that can be used in vitro and in vivo. First, the well sizes and numbers were adjusted for 3D cell culture and in vitro screening of molecules. Then, the functionality of the wells was evaluated in vivo under 36 conditions for tissue regeneration involving human mesenchymal stem cells (hMSCs) and bovine primary chondrocytes (bPCs) screened in one animal. Each biocompatible well was controlled to contain μl-size volumes of tissue, which led to tissue penetration from the host and tissue formation under implanted conditions. We quantified both physically and biologically the amounts of extracellular matrix (ECM) components found in each well. Using this new concept the co-culture of hMSCs and bPCs was identified as a positive hit for cartilage tissue repair, which was a comparable result using conventional methods. The in vivo screening of candidate conditions opens an entirely new range of experimental possibilities, which significantly abates experimental animal use and increases the pace of discovery of medical treatments.
authors: Screvo Ltd, Enschede, The Netherlands. gustavo.higuera@screvo.net
authors: Gustavo A
authors: GA
authors: Higuera
authors: Jeanine A A
authors: JA
authors: Hendriks
authors: Joost
authors: J
authors: van Dalum
authors: Ling
authors: L
authors: Wu
authors: Roka
authors: R
authors: Schotel
authors: Liliana
authors: L
authors: Moreira-Teixeira
authors: Mirella
authors: M
authors: van den Doel
authors: Jeroen C H
authors: JC
authors: Leijten
authors: Jens
authors: J
authors: Riesle
authors: Marcel
authors: M
authors: Karperien
authors: Clemens A
authors: CA
authors: van Blitterswijk
authors: Lorenzo
authors: L
authors: Moroni
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002417:Cattle; D019902:Chondrocytes / Q000737:chemistry* / Q000166:cytology; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000737:chemistry* / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D001672:Biocompatible Materials