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      Biomaterials for Local, Controlled Drug Delivery to the Injured Spinal Cord

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          Abstract

          Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present studies using a variety of biomaterials, including hydrogels, particles, and fibers/conduits for drug delivery. Subsequently, we discuss how each may be manipulated to optimize drug release during a specific time frame following SCI. Developing polymer biomaterials that can effectively release drug to target specific aspects of SCI pathophysiology will result in more efficacious approaches leading to better regeneration and recovery following SCI.

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          Most cited references157

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          Nanometre diameter fibres of polymer, produced by electrospinning

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            Epidemiology, demographics, and pathophysiology of acute spinal cord injury.

            Spinal cord injury occurs through various countries throughout the world with an annual incidence of 15 to 40 cases per million, with the causes of these injuries ranging from motor vehicle accidents and community violence to recreational activities and workplace-related injuries. Survival has improved along with a greater appreciation of patterns of presentation, survival, and complications. Despite much work having been done, the only treatment to date known to ameliorate neurologic dysfunction that occurs at or below the level of neurologic injury has been intravenous methylprednisolone therapy. Much research over the past 30 to 40 years has focused on elucidating the mechanisms of spinal cord injury, with the complex pathophysiologic processes slowly being unraveled. With a greater understanding of both primary and secondary mechanisms of injury, the roles of calcium, free radicals, sodium, excitatory amino acids, vascular mediators, and apoptosis have been elucidated. This review examines the epidemiology, demographics, and pathophysiology of acute spinal cord injury.
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              Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering.

              Nerve tissue engineering is one of the most promising methods to restore nerve systems in human health care. Scaffold design has pivotal role in nerve tissue engineering. Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue-engineering applications. Random and aligned PCL/gelatin biocomposite scaffolds were fabricated by varying the ratios of PCL and gelatin concentrations. Chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by FTIR, porometry, contact angle and tensile measurements, while the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. PCL/gelatin 70:30 nanofiber was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (C17.2 cells). MTS assay and SEM results showed that the biocomposite of PCL/gelatin 70:30 nanofibrous scaffolds enhanced the nerve differentiation and proliferation compared to PCL nanofibrous scaffolds and acted as a positive cue to support neurite outgrowth. It was found that the direction of nerve cell elongation and neurite outgrowth on aligned nanofibrous scaffolds is parallel to the direction of fibers. PCL/gelatin 70:30 nanofibrous scaffolds proved to be a promising biomaterial suitable for nerve regeneration.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                10 May 2017
                2017
                : 8
                : 245
                Affiliations
                [1]Department of Biomedical Engineering and Center for Biotechnology and Interdisciplinary Sciences, Rensselaer Polytechnic Institute, Troy NY, USA
                Author notes

                Edited by: Peregrine B. Osborne, University of Melbourne, Australia

                Reviewed by: Giles Plant, Stanford University, USA; Weien Yuan, Shanghai Jiao Tong University, China

                *Correspondence: Ryan J. Gilbert, gilber2@ 123456rpi.edu

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2017.00245
                5423911
                28539887
                bcc0ab29-2b3d-478b-b4d0-12587f7b10b0
                Copyright © 2017 Ziemba and Gilbert.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 08 February 2017
                : 19 April 2017
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 197, Pages: 20, Words: 0
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01NS092754
                Funded by: National Science Foundation 10.13039/100000001
                Award ID: Career 1150125
                Award ID: Graduate Research Fellowship DGE-1247271
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                spinal cord injury,inflammation,regeneration,drug delivery,biomaterials,hydrogels,particles,fibers

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