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BIM289A Final - Regeneration of Central Nervous System...

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Unformatted text preview: Regeneration of Central Nervous System Injuries by Application of a Bioactive Polymer Scaffold Seeded with Autologous Neural Stem Cells Harold J. Ting Department of Biomedical Engineering, University of California at Davis, Davis CA Central Nervous Damage Spinal Cord Injuries Degenerative Neurological Diseases (Parkinson's, Huntington's, Lou Gehrig's) Difficulties in CNS Repair Inhibitory glycoproteins associated with myelin (myelin-associated glycoprotein, oligodendrocyte myelin glycoprotein) Developmentally repulsive cues (semaphorins, ephrins, etc) Blood-spine barrier "Reactive astrocytes" Possible Interventions Necessary Components for Successful CNS Defect Intervention Device Elements Photolithographic Micropatterning Mitogen Loaded Microspheres Magnetically Aligned Collagen Polypyrrole Surface Treatment Autologous Nervous Stem Cells Surgical Implantation and Immobilization Biodegradability/Porosity Collagen Gel Rod High biocompatibility, low inflammatory index Readily biodegradable, inert byproducts Reasonably porous, allows for diffusion of nutrients, wastes, gas exchange and cellular cues. Controlled Release of Growth Factors Microspheres loaded with mitogen along a chemical gradient Surface modifications are highly regulated spatially, but remain porous. Electrical Activity Polypyrrole is electrically conductive. Electric fields enhance nervous tissue migration and proliferation Transiently generates electric potentials Applied via Ink-Jet Printer technology. Oriented Nervous Substratum Collagen gel is magnetically aligned along the axis of preferred axonal growth. Microspheres will establish a chemical gradient for NGF. Micropatterning will present a path of least resistance for cellular migration. Isolation of NSCs Biopsies will be performed to isolate promising tissue samples. In the future, NCS's derived from non invasive regions may be developed. Unfortunately, currently highly invasive, though only minute amounts need be recovered. NCS can be derived from dermis, blood, or blood marrow but difficult to isolate from large populations of other cells. In the future, NCS's derived from these noninvasive regions may be developed. Incorporation of Support Cells Isolated NSC's will be added to the fully synthesized polymer implant. These will then differentiate primarily into neuroglial cells due to mitotic cues (NGF and nanofiber substrate of implant) in the culture system. Implant walls will serve to delay astrocyte migration preventing additional glial cap formation, but after degradation will allow for later development of fully functional nervous tissue. References 1. Schwab ME, Kapfhammer JP, Bandtlow CE. Inhibitors of neurite growth. Annu Rev Neurosci. 1993;16:565-95. Neurosci. 2. Filbin MT. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci. 2003;4:703-13. Neurosci. 3. Asher RA, Morgenstern DA, Moon LD, Fawcett JW. Chondroitin sulphate proteoglycans: inhibitory components of the glial scar. Prog Brain Res. 2001;132:611-9. Res. 4. Cai D, Qiu J, Cao Z, McAtee M, Bregman BS, Filbin MT. 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