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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.