Functional Recovery Following Spinal Cord Hemisection Mediated by a Unique Polymer Scaffold Seeded with Neural Stem Cell
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Functional Recovery Following Spinal Cord Hemisection Mediated by a Unique Polymer Scaffold Seeded with Neural Stem Cells 1
2 3 2 2 4 Erin Lavik, Yang D. Teng, David Zurakowski, Xianlu Qu, Evan Snyder, Robert Langer
1Department of Materials Science and Engineering, MIT; 2Department of Neurology, Children’s Hospital, Boston; 3Department of Orthopedics, Children’s Hospital, Boston; 4Department of Chemical Engineering, MIT ABSTRACT A dual scaffold structure made of biodegradable polymers and seeded with neural stem cells has been developed to address the issues of spinal cord injury including axonal severance and the loss of neurons and glia. The general design of the scaffold is derived the structure of the spinal cord with an outer section which mimics the white matter with long axial pores to provide axonal guidance and an inner section seeded with neural stem cells to address the issues of cell replacement and mimic the general character of the gray matter. The seeded scaffold leads to improved functional recovery as compared with the lesion control or cells alone following spinal cord injury. INTRODUCTION Each year in the U.S. approximately 10,000 people sustain spinal cord injuries. The median age at injury is only 26 years old. While medical science has made great strides in maintaining patients with spinal cord injuries, the prognosis for recovery is very poor. 45% of those who are injured do not recover any feeling or function below the site of injury, and less than 1% of those who are injured fully recover [1]. Traumatic spinal cord injury results in the loss of neurons, supporting cells, myelin, and axonal damage or severance Encouraging results have been reported using a variety of approaches [2, 3] including scaffolds [4-7]. It appears that given a hospitable environment, the spinal cord can regenerate following injury. We hypothesized that such an environment might be created using a tissue engineered implant which incorporated neural stem cells into a three dimensional biodegradable polymer scaffold to mimic the general structure of the spinal cord. The spinal cord consists of two major components: the gray matter at the center of the cord, which is composed of the cell bodies of the axons and glia, and the white matter at the outside of the cord which consists of the long, axonal tracts. To mimic this structure, a dual implant consisting of inner and outer scaffolds was designed. The inner scaffold was designed to support the seeding of cells to replace those lost after SCI, and the outer portion was designed to have axially oriented pores to for axonal guidance (Figure 1). Neural stem cells, specifically the C17.2 clone, were seeded on the implant to hopefully replace cells lost during injury. These cells have been shown to be capable of differentiating in vivo into all the cell types of the central nervous system[8]. EXPERIMENTAL METHODS Both the inner and outer scaffolds were fabricated from a blend of 75% 50:50 poly(lacticco-glycolic acid) (PLGA) ( Mn ~40,000) and 25% a block copolymer of poly(lac
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