title: Nanofibrous Patches for Spinal Cord Regeneration.
abstract: The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here we developed scaffolds with aligned nanofibers for nerve guidance and drug delivery in spinal cord. Blended polymers including Poly (l-lactic acid) (PLLA) and Poly (lactide-co-glycolide) (PLGA) were used to electrospin nanofibrous scaffolds with two-layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer. Rolipram, a small molecule that can enhance cAMP activity in neurons and suppress inflammatory responses, was immobilized onto nanofibers. To test the therapeutic effects of nanofibrous scaffolds, the nanofibrous scaffolds loaded with rolipram were used to bridge the hemisection lesion in 8-week old athymic rats. The scaffolds with rolipram increased axon growth through the scaffolds and in the lesion, promoted angiogenesis through the scaffold, and decreased the population of astrocytes and chondroitin sulfate proteoglycans in the lesion. Locomotor scale rating analysis showed that the scaffolds with rolipram significantly improved hindlimb function after 3 weeks. This study demonstrated that nanofibrous scaffolds offered a valuable platform for drug delivery for spinal cord regeneration.
authors: Department of Bioengineering, University of California, Berkeley ; Department of Neurosurgery, Huashan Hospital, Shanghai, China ; Department of Anesthesia and Perioperative Care, University of California, San Francisco.
authors: Yiqian
authors: Y
authors: Zhu
authors: Aijun
authors: A
authors: Wang
authors: Wenqian
authors: W
authors: Shen
authors: Shyam
authors: S
authors: Patel
authors: Rong
authors: R
authors: Zhang
authors: William
authors: W
authors: Young
authors: Song
authors: S
authors: Li
references: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9459-64
references: 19470644
references: Science. 2002 Feb 8;295(5557):1029-31
references: 11834824
references: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11915-20
references: 17615237
references: Biochem Biophys Res Commun. 2008 Aug 8;372(4):601-6
references: 18515080
references: Neuron. 2002 Jun 13;34(6):885-93
references: 12086637
references: Nat Rev Neurosci. 2006 Aug;7(8):617-27
references: 16858390
references: Nano Lett. 2006 Mar;6(3):537-42
references: 16522058
references: J Neurosci. 2002 Apr 1;22(7):2792-803
references: 11923444
references: J Cereb Blood Flow Metab. 2007 Jun;27(6):1096-107
references: 17033690
references: Nano Lett. 2007 Jul;7(7):2122-8
references: 17567179
references: J Neurosci. 1999 Oct 15;19(20):8979-89
references: 10516316
references: Neurosurgery. 2002 Sep;51(3):742-51; discussion 751-2
references: 12188954
references: Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80
references: 18321149
references: Annu Rev Neurosci. 2004;27:341-68
references: 15217336
references: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3024-9
references: 11867737
references: Biomaterials. 2008 May;29(13):1989-2006
references: 18281090
references: J Cell Sci. 1995 Mar;108 ( Pt 3):1307-15
references: 7622613
references: Neuroscience. 2003;120(4):951-60
references: 12927201
references: Inflammation. 1993 Jun;17(3):333-44
references: 7687237
references: Adv Drug Deliv Rev. 2007 Dec 10;59(14):1392-412
references: 17884240
references: Exp Neurol. 2008 Feb;209(2):294-301
references: 17617407
references: J Neurosci. 2003 Oct 15;23(28):9276-88
references: 14561854
references: Science. 1998 Sep 4;281(5382):1515-8
references: 9727979
references: J Neurol Sci. 2005 Jun 15;233(1-2):43-7
references: 15949495
references: Neuroscientist. 2001 Aug;7(4):325-39
references: 11488398
references: J Neurotrauma. 1995 Feb;12(1):1-21
references: 7783230
references: CNS Drug Rev. 2001 Winter;7(4):387-98
references: 11830756
references: Nature. 2000 Jan 27;403(6768):439-44
references: 10667797
references: Neurosci Lett. 2007 May 17;418(2):165-9
references: 17398001
references: J Neurosci. 2008 Apr 2;28(14):3814-23
references: 18385339
references: Biomaterials. 2001 May;22(10):1125-36
references: 11352092
references: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8786-90
references: 15173585
references: Front Biosci. 2004 May 01;9:1422-32
references: 14977557
references: Neuron. 1994 Sep;13(3):757-67
references: 7522484
references: Neurosurg Focus. 2008;25(5):E2
references: 18980476
references: J Neurotrauma. 2006 Mar-Apr;23(3-4):335-44
references: 16629620
references: J Neurosci. 1991 Nov;11(11):3398-411
references: 1719160
references: Exp Neurol. 2009 Apr;216(2):490-8
references: 19320007