Functional recovery after peripheral nerve injury and implantation of a collagen guide Olivier Alluin a , Catherine Wittmann b , Tanguy Marqueste a , Jean-François Chabas c, d , Ste ´ phane Garcia e , Marie-Noe ¨lle Lavaut e , Didier Guinard d , François Feron c , Patrick Decherchi a, * a UMR CNRS 6233, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe « Plasticite´ des Syste`mes Nerveux et Musculaires », Universite´delaMe´diterrane ´e (Aix-Marseille II), Aix-Marseille Universite´, Parc Scientifique et Technologique de Luminy, Faculte´ des Sciences du Sport de Marseille, Case Postale 910, 163, avenue de Luminy, 13288 Marseille Cedex 09, France b Universite´ de Lyon, UPSP 2007.03.135 RTI2B « Re ´parationTissulaire, Interactions Biologiques et Biomate´riaux », Universite ´ Claude Bernard Lyon I, Institut des Sciences Pharmaceutiques et Biologiques (ISPB), 8, avenue Rockefeller, 69673 Lyon Cedex 08, France c Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (CNRS UMR 6184), Universite´ de la Me´diterrane´e (Aix-Marseille II), Aix-Marseille Universite´, Institut Fe ´de´ratif de Recherche Jean ROCHE (IFR11), Faculte ´ de Me´decine (Secteur Nord), 51, boulevard Pierre Dramard,13015 Marseille, France d Services de Chirurgie de la Main, Chirurgie Plastique et Re ´paratrice des Membres, Assistance Publique, Ho ˆpitaux de Marseille, Ho ˆpital de la Conception, 147, boulevard Baille, 13385 Marseille Cedex 05, France e Service Hospitalier d’Anatomie et Cytologie Pathologiques Humaines, Universite´ de la Me´diterrane´e (Aix-Marseille II), Aix-Marseille Universite´, Assistance Publique, Ho ˆpitaux de Marseille, Institut de Cance´rologie et d’Immunologie de Marseille (IFR 137), Faculte ´ de Me´decine Nord, 51, boulevard Pierre Dramard, 13916 Marseille Cedex 20, France article info Article history: Received 18 July 2008 Accepted 10 September 2008 Available online 16 October 2008 Keywords: Afferent fiber Electrophysiology Nerve repair Nerve guide Collagen conduit Metabosensitivity abstract Although surgery techniques improved over the years, the clinical results of peripheral nerve repair remain unsatisfactory. In the present study, we compare the results of a collagen nerve guide conduit to the standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves. We assessed behavioral and functional sensori-motor recovery in a rat model of peroneal nerve tran- section. A 1 cm segment of the peroneal nerve innervating the Tibialis anterior muscle was removed and immediately replaced by a new biodegradable nerve guide fabricated from highly purified type I þ III collagens derived from porcine skin. Four groups of animals were included: control animals (C, n ¼ 12), transected animals grafted with either an autologous nerve graft (Gold Standard; GS, n ¼ 12) or a collagen tube filled with an acellular skeletal muscle matrix (Tube-Muscle; TM, n ¼ 12) or an empty collagen tube (Collagen-Tube; CT, n ¼ 12). We observed that 1) the locomotor recovery pattern, analyzed with kinetic parameters and peroneal functional index, was superior in the GS and CT groups; 2) a muscle contraction was obtained in all groups after stimulation of the proximal nerve but the mechanical muscle properties (twitch and tetanus threshold) parameters indicated a fast to slow fiber transition in all operated groups; 3) the muscular atrophy was greater in animals from TM group; 4) the metabosensitive afferent responses to electrically induced fatigue and to two chemical agents (KCl and lactic acid) was altered in GS, CT and TM groups; 5) the empty collagen tube supported motor axonal regeneration. Altogether, these data indicate that motor axonal regeneration and locomotor recovery can be obtained with the insertion of the collagen tube RevolNerv Ò . Future studies may include engineered conduits that mimic as closely as possible the internal organization of uninjured nerve. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Complex peripheral nerve injuries that result in extended neu- rectomy require reconstructive surgery with nerve grafts [1]. Autologous nerve grafts are currently used in the reconstruction of a peripheral nerve gap. The autologous nerve is a natural substitute, acting as a conduit for axonal regeneration. The surgical procedure, named ‘‘Gold Standard’’ technique, consists of harvesting one nerve from the patient and grafting it in between the two stumps of the transected nerve. However, grafting causes morbidity at the donor Abbreviations: C, Control; CT, Collagen-Tube; EIF, Electrical Induced Fatigue; GS, Gold Standard; PFI, Peroneal Functional Index; PPD, p-Phenylenediamine; TM, Tube-Muscle. * Corresponding author. Tel./fax: þ33 4 91 82 84 09. E-mail address: patrick.decherchi@univmed.fr (P. Decherchi). URL: http://www.physiologie.staps.univ-mrs.fr Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2008.09.043 Biomaterials 30 (2009) 363–373