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WIREs Nanomed Nanobiotechnol
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Hydrogel mediated delivery of trophic factors for neural repair

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Abstract Neurotrophins have been implicated in a variety of diseases and their delivery to sites of disease and injury has therapeutic potential in applications including spinal cord injury, Alzheimer's disease, and Parkinson's disease. Biodegradable polymers, and specifically, biodegradable water‐swollen hydrogels, may be advantageous as delivery vehicles for neurotrophins because of tissue‐like properties, tailorability with respect to degradation and release behavior, and a history of biocompatibility. These materials may be designed to degrade via hydrolytic or enzymatic mechanisms and can be used for the sustained delivery of trophic factors in vivo. Hydrogels investigated to date include purely synthetic to purely natural, depending on the application and intended release profiles. Also, flexibility in material processing has allowed for the investigation of injectable materials, the development of scaffolding and porous conduits, and the use of composites for tailored molecule delivery profiles. It is the objective of this review to describe what has been accomplished in this area thus far and to remark on potential future directions in this field. Ultimately, the goal is to engineer optimal biomaterials to deliver molecules in a controlled and dictated manner that can promote regeneration and healing for numerous neural applications. Copyright © 2008 John Wiley & Sons, Inc. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease

Examples of techniques for in situ gelation of hydrogel solutions. (a) For agarose, nitrogen is passed from the tank through a bath of dry ice and acetone (box) through an aluminum rod surrounded by dry ice to cool the solution and induce gelation. (b) Shear forces, induced through syringe injection, allow methylcellulose and acetate‐modified hyaluronan (HAMC) gels to flow and then re‐gel at physiological temperatures in vivo, potentially in the intrathecal space.

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PLGA porous nerve conduits. (a, b) Schematics for fabrication of single and multiple lumen conduits, respectively. (c, d) Images of single and multiple lumen porous conduits. Scale bars: (c) 700µm, (d) 500µm. (Reprinted, with permission, from Ref. 82. Copyright 2005 Elsevier).

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Schematic of growth factor immobilization to a fibrin matrix through interactions with heparin. (Reprinted, with permission, from Ref. 76. Copyright 2006 Elsevier).

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Aligned agarose nerve tubes synthesized by ice crystallization. (a, b) SEM images of freeze‐dried tubes a| longitudinally and (b) cross‐sectionally. (c) Axonal penetration in vivo through the agarose tubes. Scale bars = 100µm. (Reprinted, with permission, from Ref. 63. Copyright 2006 Elsevier).

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Insertion of collagen‐filled HEMA‐co‐MMA nerve tubes into a complete transection spinal cord injury. (a) Injury pre‐insertion. (b) Filling of tubes with collagen. (c) Half‐implanted tube. (d) Fully‐inserted nerve tube at site of injury. (Reprinted, with permission, from Ref. 57. Copyright 2006 Elsevier).

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(a) Structure of PEG modified with degradable groups and reactive acrylates to allow for degradation and photopolymerization, respectively. (b) Cumulative release of neurotrophins ciliary‐neurotrophic factor (CNTF) (●), BDNF (⧫), and NT‐3 (▪) from 10 wt% PEG hydrogels. (Reprinted, with permission, from Ref. 48. Copyright 2006 Elsevier).

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