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Functional motor recovery is improved due to local placement of GDNF microspheres after delayed nerve repair

Authors

  • Matthew D. Wood,

    Corresponding author
    1. Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; telephone: 416-813-7654 ext. 28342; fax: 416-813-6637
    2. Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    • Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; telephone: 416-813-7654 ext. 28342; fax: 416-813-6637.
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  • Tessa Gordon,

    1. Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; telephone: 416-813-7654 ext. 28342; fax: 416-813-6637
    2. Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
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  • Stephen W.P. Kemp,

    1. Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; telephone: 416-813-7654 ext. 28342; fax: 416-813-6637
    2. Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
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  • Edward H. Liu,

    1. Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; telephone: 416-813-7654 ext. 28342; fax: 416-813-6637
    2. Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
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  • Howard Kim,

    1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
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  • Molly S. Shoichet,

    1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
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  • Gregory H. Borschel

    1. Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8; telephone: 416-813-7654 ext. 28342; fax: 416-813-6637
    2. Program in Physiology and Experimental Medicine, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
    4. Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
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  • The authors have no financial disclosures to reveal.

Abstract

The majority of bioengineering strategies to promote peripheral nerve regeneration after injury have focused on therapies to bridge large nerve defects while fewer therapies are being developed to treat other nerve injuries, such as nerve transection. We constructed delivery systems using fibrin gels containing either free GDNF or polylactide–glycolic acid (PLGA) microspheres with GDNF to treat delayed nerve repair, where ELISA verified GDNF release. We determined the formulation of microspheres containing GDNF that optimized nerve regeneration and functional recovery in a rat model of delayed nerve repair. Experimental groups underwent delayed nerve repair and treatment with GDNF microspheres in fibrin glue at the repair site or control treatments (empty microspheres or free GDNF without microspheres). Contractile muscle force, muscle mass, and MUNE were measured 12 weeks following treatment, where GDNF microspheres (2 weeks formulation) were superior compared to either no GDNF or short-term release of free GDNF to nerve. Nerve histology distal to the repair site demonstrated increased axon counts and fiber diameters due to GDNF microspheres (2 weeks formulation). GDNF microspheres partially reversed the deleterious effects of chronic nerve injury, and recovery was slightly favored with the 2 weeks formulation compared to the 4 weeks formulation. Biotechnol. Bioeng. 2013; 110: 1272–1281. © 2012 Wiley Periodicals, Inc.

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