Development of transplantable nervous tissue constructs comprised of stretch-grown axons.
Pursuing a new approach to nervous system repair, fasciculated axon tracts grown in vitro were developed into nervous tissue constructs designed to span peripheral nerve or spinal cord lesions. We optimized the newfound process of extreme axon stretch growth to maximize the number and length of axon tracts, reach an unprecedented axon growth-rate of 1cm/day, and create 5cm long axon tracts in 8 days to serve as the core component of a living nervous tissue construct. Immunocytochemical analysis confirmed that elongating fibers were axons, and that all major cytoskeletal constituents were present across the stretch-growth regions. We formed a transplantable nervous tissue construct by encasing the elongated cells in an 80% collagen hydrogel, removing them from culture, and inserting them into a synthetic conduit. Alternatively, we induced axon stretch growth directly on a surgical membrane that could be removed from the elongation device, and formed into a cylindrical construct suitable for transplant. The ability to rapidly create living nervous tissue constructs that recapitulates the uniaxial orientations of the original nerve offers an unexplored and potentially complimentary direction in nerve repair. Ideally, bridging nerve damage with living axon tracts may serve to establish or promote new functional connections.
Pfister
Bryan J
BJ
Department of Neurosurgery, Center for Brain Injury Repair, University of Pennsylvania, 3320 Smith Walk, 105 Hayden Hall, Philadelphia, PA 19104, USA. pfister@njit.edu
Iwata
Akira
A
Taylor
Andrew G
AG
Wolf
John A
JA
Meaney
David F
DF
Smith
Douglas H
DH
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000637:transplantation* / Q000648:ultrastructure; D001705:Bioprosthesis; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D049108:Cell Enlargement; D002478:Cells, Cultured; D004548:Elasticity; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D010812:Physical Stimulation / Q000295:instrumentation* / Q000379:methods; D051381:Rats; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*