1. ¹Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA
2. ²Department of Physical Medicine and Rehabilitation, University of California, Irvine, California, USA
3. ³Reeve-Irvine Research Center, Irvine, California, USA

Correspondence: Lonnie D. Shea, Department of Chemical Engineering, Northwestern University, 2145 Sheridan Road/E156, Evanston, Illinois 60208-3120, USA. E-mail: l-shea@northwestern.edu

Received 14 February 2008; Accepted 17 October 2008; Published online 2 December 2008.

Abstract

The regeneration of tissues with complex architectures requires strategies that promote the appropriate cellular processes, and can direct their organization. Plasmid-loaded multiple channel bridges were engineered for spinal cord regeneration with the ability to support and direct cellular processes and promote gene transfer at the injury site. The bridges were manufactured with a gas foaming technique, and had multiple channels with controllable diameter and encapsulated plasmid. Initial studies investigating bridge implantation subcutaneously (SC) indicated transgene expression in vivo for 44 days, with gene expression dependent upon the pore size of the bridge. In the rat spinal cord, bridges implanted into a lateral hemisection supported substantial cell infiltration, aligned cells within the channels, axon growth across the channels, and high levels of transgene expression at the implant site with decreasing levels rostral and caudal. Immunohistochemistry revealed that the transfected cells at the implant site were present in both the pores and channels of the bridge and were mainly identified as Schwann cells, fibroblasts, and macrophages, in descending order of transfection. This synergy between gene delivery and the scaffold architecture may enable the engineering of tissues with complex architectures.