A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve regeneration

Alternatives to autografts have long been sought for use in bridging neural gaps. Many entubulation materials have been studied, although with general ly disappointing results in comparison with autografts. The purpose of this study was to design a more effective neural guidance conduit, to introduce Schwann cells into the conduit, and to determine regenerative capability t hrough it fn an in vivo model. A novel, fully biodegradable polymer conduit was designed and fabricated for use in peripheral nerve repair, which appr oximates the macro- and microarchitecture of native peripheral nerves. It c omprised a series of longitudinally aligned channels, with diameters rangin g from 60 to 550 microns. The lumenal surfaces promoted the adherence of Sc hwann cells, whose presence is known to play a key role in nerve regenerati on. This unique channel architecture increased the surface area available f or Schwann cell adherence up to five-fold over that available through a sim ple hollow conduit. The conduit was composed of a high-molecular-weight cop olymer of lactic and glycolic acids (PLGA) (MW 130,000) in an 85:15 monomer ratio. A novel foam-processing technique, employing low-pressure injection molding, was used to create highly porous conduits (approximately 90% pore volume) with continuous longitudinal channels. Using this technique, condu its were constructed containing 1, 5, 16, 45, or more longitudinally aligne d channels. Prior to cellular seeding of these conduits, the foams were pre wet with 50% ethanol, flushed with physiologic saline, and coated with lami nin solution (10 mu g/mL). A Schwann cell suspension was dynamically introd uced into these processed foams at a concentration of 5 X 10(5) cells/mL, u sing a simple bioreactor flow loop. In vivo regeneration studies were carri ed out in which cell-laden five-channel polymer conduits (individual channe l ID 500 mu m, total conduit OD 2.3 mm) were implanted across a 7-mm gap in the rat sciatic nerve (n = 4), and midgraft axonal regeneration compared w ith autografts (n = 6). At 6 weeks, axonal regeneration was observed in the midconduit region of all five channels in each experimental animal, The cr oss-sectional area comprising axons relative to the open conduit cross sect ional area (mean 26.3%, SD 10.1%) compared favorably with autografts (mean 23.8%, SD 3.6%). Our methodology can be used to create polymer foam conduit s containing longitudinally aligned channels, to introduce Schwann cells in to them, and to implant them into surgically created neural defects. These conduits provide an environment permissive to axonal regeneration. Furtherm ore, this polymer foam-processing method and unique channeled architecture allows the introduction of neurotrophic factors into the conduit in a contr olled fashion. Deposition of different factors into distinct regions within the conduit may be possible to promote more precisely guided neural regene ration.