Inverted human umbilical arteries with tunable wall thicknesses for nerve regeneration Thomas Crouzier, Trosper McClendon, Zehra Tosun, Peter S. McFetridge School of Chemical, Biological and Materials Engineering, The University of Oklahoma Bioengineering Center, University of Oklahoma, 100 East Boyd Street, Norman, Oklahoma 73019-1004 Received 25 August 2007; revised 18 January 2008; accepted 12 February 2008 Published online 9 July 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.32103 Abstract: Tubular nerve guides have shown a potential to bridge nerve defects, by directing neuronal elongation, localizing growth factors, and inhibiting fibrotic cellular ingrowth. These investigations describe a novel acellular scaffold derived from the human umbilical cord artery that aims to enhance nerve regeneration by presenting a unique mechanical and chemical environment to the dam- aged nerve ends. A rapid, semiautomated dissection tech- nique is described that isolates the human umbilical artery (HUA) from the umbilical cord, after which the vessel is decellularized using sodium dodecyl sulfate (SDS). The artery is turned inside out to produce a 3D scaffold, that unlike previous vessels for nerve repair, is more resistant to collapse. The scaffold has the potential as either an acel- lular bridge-implant, or for in vitro nerve regeneration. Stress–strain relationships and suture retention were assessed to determine whether the material had similar mechanical properties to native nerves. A dual process- flow perfusion bioreactor was developed to assess glucose mass transfer, and to investigate the culture of neuronal- like PC12 cells within the scaffold. These investigations have shown the automated dissecting method yields a smooth tubular scaffold, where wall thickness can be tuned to alter the mechanical behavior of the scaffold. Inverting the scaffold prevents collapse, with the decellu- larized iHUA having comparable mechanical properties to native nerves. Bioreactor cultures with PC12 cells seeded within iHUA lumenal void were shown to adhere and migrate into the preexisting ECM after 11 days of culture. These investigations show the potential of the iHUA as a unique 3D scaffold that may enhance nerve regeneration. Ó 2008 Wiley Periodicals, Inc. J Biomed Mater Res 89A: 818–828, 2009 Key words: umbilical artery; tissue engineering; nerve; nerve guide INTRODUCTION In the United States, more than 50,000 surgical procedures are carried out to repair peripheral nerves annually. In addition to loss of function and disability; treatment costs have a significant econom- ical impact. 1,2 As a result, research efforts toward developing efficient repair techniques to bridge sev- ered nerves are actively sort. Earlier techniques, such as end-to-end microsutures, were shown to improve nerve function; however, autograft harvesting and relocation remains the ‘‘gold standard’’ for clinical treatment. Although these treatments have been suc- cessful over smaller defects, there remains a clinical need to bridge larger defects, and minimize the need to use autologous tissue in which secondary injuries are induced. Tubular guidance channels have had some success with smaller defects by providing a supportive ma- trix that prevents fibrous tissue infiltration, and allows growth factors secreted by the nerve stumps to be concentrated to promote axonal elongation. 3 The tissue engineering approaches aims to further improve regeneration, by implanting partially (or wholly) grown neo-nerve tissue to bridge the defect. Current materials can be grouped into several dis- tinct categories; autologous tissue grafts, nonautolo- gous tissue and acellular grafts, natural-based mate- rials, and synthetic materials. Although significant progress has been made in recent years, little is known of the regenerative process, due predomi- nantly to the complexity of healing phenomena. This problem has been attenuated by the difficulty in rec- reating the wound in an artificial environment to facilitate our understanding of these biological proc- esses. However, identifying ideal materials that pro- mote nerve regeneration without undesirable side effects remains an active area of research. Previous investigations have shown the utility of nonnervous autologous tissue grafts. In particular, Correspondence to: P. S. McFetridge; e-mail: pmcfetridge@ ou.edu Ó 2008 Wiley Periodicals, Inc.