Methods for promoting the revascularization and reenervation of CNS lesions
The present invention provides methods of promoting the revascularization and/or reenervation of central nervous system lesions using an in-situ crosslinkable hydrogel. The present invention also provides methods of treating a spinal cord injury by topically delivering to the spinal cord injury site a vehicle comprising a neurotrophic factor and/or anti-inflammatory agent. Also provided are methods of treating a spinal cord injury by topically administering or delivering a hydrogel to the injury site.
1. A method of treating a spinal cord injury, comprising topically delivering to the spinal cord injury site an amount of a neurotrophic factor and/or an anti-inflammatory agent effective to treat the spinal cord injury, wherein the neurotrophic factor and/or the anti-inflammatory agent is in a hydrogel comprising chitosan, gelatin and a crosslinker, wherein the hydrogel is delivered to the spinal cord injury site as a liquid and gels in situ.
2. The method of claim 1 , wherein the spinal cord injury is an acute spinal cord injury.
3. The method of claim 1 , wherein the hydrogel comprises a covalent crosslinker and an ionic crosslinker.
4. The method of claim 3 , wherein the covalent crosslinker is genipin.
5. The method of claim 3 , wherein the ionic crosslinker is glycerol phosphate.
6. The method of claim 3 , wherein the covalent crosslinker is added to a chitosan and gelatin mixture prior to addition of the ionic crosslinker.
7. The method of claim 1 , wherein the neurotrophic factor is glial derived neurotrophic factor (GDNF).
8. A method of treating a spinal cord injury, comprising topically delivering to the spinal cord injury site an amount of a hydrogel effective to treat the spinal cord injury, wherein the hydrogel comprises chitosan, gelatin and a crosslinker, wherein the hydrogel is delivered to the spinal cord injury site as a liquid and gels in situ.
9. The method of claim 8 , wherein the spinal cord injury is an acute spinal cord injury.
10. The method of claim 8 , wherein the hydrogel comprises a neurotrophic factor and/or an anti-inflammatory agent.
11. The method of claim 10 , wherein the neurotrophic factor is glial derived neurotrophic factor (GDNF).
12. A method of reducing inhibition of axonal regeneration at a spinal cord injury site, comprising topically delivering to the site an amount of a hydrogel effective in reducing inhibition of axonal regeneration at the spinal cord injury site, wherein the hydrogel comprises chitosan, gelatin and a crosslinker, wherein the hydrogel is delivered to the spinal cord injury site as a liquid and gels in situ.
13. The method of claim 12 , wherein the hydrogel comprises a neurotrophic factor and/or an anti-inflammatory agent.
14. The method of claim 13 , wherein the neurotrophic factor is glial derived neurotrophic factor (GDNF).
15. A method of decreasing secondary injury at a spinal cord injury site, comprising topically delivering to the site an amount of a hydrogel effective in decreasing secondary injury at the spinal cord injury site, wherein the hydrogel comprises chitosan, gelatin and a crosslinker, wherein the hydrogel is delivered to the spinal cord injury site as a liquid and gels in situ.
16. The method of claim 15 , wherein the spinal cord injury is an acute spinal cord injury.
17. The method of claim 15 , wherein the hydrogel comprises a neurotrophic factor and/or an anti-inflammatory agent.
18. The method of claim 17 , wherein the neurotrophic factor is glial derived neurotrophic factor (GDNF).