Neurotrophin releasing single and multiple lumen nerve conduits.
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.
Yang
Yang
Y
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd E156, Evanston, IL 60208-3120, USA.
De Laporte
Laura
L
Rives
Christopher B
CB
Jang
Jae-Hyung
JH
Lin
Wei-Chun
WC
Shull
Kenneth R
KR
Shea
Lonnie D
LD
D020341:Absorbable Implants; D000818:Animals; D002642:Chick Embryo; D003692:Delayed-Action Preparations; D004355:Drug Stability; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D019344:Lactic Acid; D008297:Male; D008422:Materials Testing; D051379:Mice; D008815:Mice, Inbred Strains; D008863:Microspheres; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016501:Neurites / Q000502:physiology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D016062:Porosity; D023822:Tissue Engineering
D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020932:Nerve Growth Factor