Vascular Endothelial Growth Factor and Fibroblast Growth Factor 2 Delivery from Spinal Cord Bridges to Enhance Angiogenesis Following Injury

Overview

Journal J Biomed Mater Res A

Specialty Biomedical Engineering

Date 2011 Jun 2

PMID 21630429

Citations 14

Authors

Laura De Laporte

Anne des Rieux

Hannah M Tuinstra

Marina L Zelivyanskaya

Nora M De Clerck

Andrei A Postnov

Veronique Preat

Lonnie D Shea

Affiliations

Soon will be listed here.

Abstract

The host response to spinal cord injury can lead to an ischemic environment that can induce cell death and limits cell transplantation approaches to promote spinal cord regeneration. Spinal cord bridges that provide a localized and sustained release of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were investigated for their ability to promote angiogenesis and nerve growth within the injury. Bridges were fabricated by fusion of poly(lactide-co-glycolide) microspheres using a gas foaming/particulate leaching technique, and proteins were incorporated by encapsulation into the microspheres and/or mixing with the microspheres before foaming. Compared to the mixing method, encapsulation reduced the losses during leaching and had a slower protein release, while VEGF was released more rapidly than FGF-2. In vivo implantation of bridges loaded with VEGF enhanced the levels of VEGF within the injury at 1 week, and bridges releasing VEGF and FGF-2 increased the infiltration of endothelial cells and the formation of blood vessel at 6 weeks postimplantation. Additionally, substantial neurofilament staining was observed within the bridge; however, no significant difference was observed between bridges with or without protein. Bridges releasing angiogenic factors may provide an approach to overcome an ischemic environment that limits regeneration and cell transplantation-based approaches.

Citing Articles

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References

Krum J, Mani N, Rosenstein J . Angiogenic and astroglial responses to vascular endothelial growth factor administration in adult rat brain. Neuroscience. 2002; 110(4):589-604. DOI: 10.1016/s0306-4522(01)00615-7. View

Storkebaum E, Lambrechts D, Carmeliet P . VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 2004; 26(9):943-54. DOI: 10.1002/bies.20092. View

Yang Y, De Laporte L, Rives C, Jang J, Lin W, Shull K . Neurotrophin releasing single and multiple lumen nerve conduits. J Control Release. 2005; 104(3):433-46. PMC: 2648409. DOI: 10.1016/j.jconrel.2005.02.022. View

Stokols S, Tuszynski M . Freeze-dried agarose scaffolds with uniaxial channels stimulate and guide linear axonal growth following spinal cord injury. Biomaterials. 2005; 27(3):443-51. DOI: 10.1016/j.biomaterials.2005.06.039. View

Ferrara N, Alitalo K . Clinical applications of angiogenic growth factors and their inhibitors. Nat Med. 1999; 5(12):1359-64. DOI: 10.1038/70928. View

Jones L, Oudega M, Bunge M, Tuszynski M . Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury. J Physiol. 2001; 533(Pt 1):83-9. PMC: 2278599. DOI: 10.1111/j.1469-7793.2001.0083b.x. View

De Laporte L, Yan A, Shea L . Local gene delivery from ECM-coated poly(lactide-co-glycolide) multiple channel bridges after spinal cord injury. Biomaterials. 2009; 30(12):2361-8. PMC: 2752148. DOI: 10.1016/j.biomaterials.2008.12.051. View

Shen Q, Goderie S, Jin L, Karanth N, Sun Y, Abramova N . Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science. 2004; 304(5675):1338-40. DOI: 10.1126/science.1095505. View

von Degenfeld G, Banfi A, Springer M, Wagner R, Jacobi J, Ozawa C . Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. FASEB J. 2006; 20(14):2657-9. DOI: 10.1096/fj.06-6568fje. View

10.

Hobson M, Green C, Terenghi G . VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J Anat. 2001; 197 Pt 4:591-605. PMC: 1468175. DOI: 10.1046/j.1469-7580.2000.19740591.x. View

11.

Asahara T, Bauters C, Zheng L, Takeshita S, Bunting S, Ferrara N . Synergistic effect of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in vivo. Circulation. 1995; 92(9 Suppl):II365-71. DOI: 10.1161/01.cir.92.9.365. View

12.

Yang Y, De Laporte L, Zelivyanskaya M, Whittlesey K, Anderson A, Cummings B . Multiple channel bridges for spinal cord injury: cellular characterization of host response. Tissue Eng Part A. 2009; 15(11):3283-95. PMC: 2792065. DOI: 10.1089/ten.TEA.2009.0081. View

13.

Sheridan M, Shea L, Peters M, Mooney D . Bioabsorbable polymer scaffolds for tissue engineering capable of sustained growth factor delivery. J Control Release. 2000; 64(1-3):91-102. DOI: 10.1016/s0168-3659(99)00138-8. View

14.

Ruiz de Almodovar C, Lambrechts D, Mazzone M, Carmeliet P . Role and therapeutic potential of VEGF in the nervous system. Physiol Rev. 2009; 89(2):607-48. DOI: 10.1152/physrev.00031.2008. View

15.

Kaigler D, Wang Z, Horger K, Mooney D, Krebsbach P . VEGF scaffolds enhance angiogenesis and bone regeneration in irradiated osseous defects. J Bone Miner Res. 2006; 21(5):735-44. DOI: 10.1359/jbmr.060120. View

16.

Riddle K, Kong H, Leach J, Fischbach C, Cheung C, Anseth K . Modifying the proliferative state of target cells to control DNA expression and identifying cell types transfected in vivo. Mol Ther. 2007; 15(2):361-8. DOI: 10.1038/sj.mt.6300017. View

17.

Widenfalk J, Lipson A, Jubran M, Hofstetter C, Ebendal T, Cao Y . Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience. 2003; 120(4):951-60. DOI: 10.1016/s0306-4522(03)00399-3. View

18.

Jang J, Rives C, Shea L . Plasmid delivery in vivo from porous tissue-engineering scaffolds: transgene expression and cellular transfection. Mol Ther. 2005; 12(3):475-83. PMC: 2648405. DOI: 10.1016/j.ymthe.2005.03.036. View

19.

Biondi M, Ungaro F, Quaglia F, Netti P . Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev. 2007; 60(2):229-42. DOI: 10.1016/j.addr.2007.08.038. View

20.

Peters M, Polverini P, Mooney D . Engineering vascular networks in porous polymer matrices. J Biomed Mater Res. 2002; 60(4):668-78. DOI: 10.1002/jbm.10134. View