Tissue engineering strategies for nerve repair employ polymer conduits termed guidance channels and bridges to promote regeneration for peripheral nerve injury and spinal cord injury, respectively. An approach for fabrication of nerve conduits with single and multiple lumens capable of controlled release of neurotrophic factors was developed. These conduits were fabricated from a mixture of poly(lactide-co-glycolide) (PLG) microspheres and porogen (NaCl) that was loaded into a mold and processed by gas foaming. The porosity and mechanical properties of the constructs were regulated by the ratio of porogen to polymer microsphere. The neurotrophin, nerve growth factor (NGF), was incorporated into the conduit by either mixing the protein with microspheres or encapsulating the protein within microspheres prior to gas foaming. A sustained release was observed for at least 42 days, with the release rate controlled by method of incorporation and polymer molecular weight. Released NGF retained its bioactivity, as demonstrated by its ability to stimulate neurite outgrowth from primary dorsal root ganglion (DRG). In vivo results indicate that conduits retain their original architecture, and allow for cellular infiltration into the channels. Polymer conduits with controllable lumen diameters and protein release may enhance nerve regeneration by guiding and stimulating neurite outgrowth.
Bibliographical noteFunding Information:
The authors would like to thank Hammad Saudye and Mark Rovedo for contributions to the conduit fabrication process, Mr. Lonnie L. Shea for fabrication of conduit molds, and Bridget Mann and Jon E. Levine (Northwestern University) for use of the radiation gamma counter. Support for this research was provided by the Christopher Reeve Paralysis Foundation (SAC2-0208-2) and NIH (R01 EB003806-01).
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science