title: Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo.
abstract: Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration.
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors: Daniel
authors: D
authors: Santos
authors: The BioRobotics Institute, Scuola Superiore Sant׳Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy.
authors: Guido
authors: G
authors: Giudetti
authors: The BioRobotics Institute, Scuola Superiore Sant׳Anna, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy; Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.
authors: Silvestro
authors: S
authors: Micera
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.
authors: Xavier
authors: X
authors: Navarro
authors: Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain. Electronic address: jaume.delvalle@uab.cat.
authors: Jaume
authors: J
authors: Del Valle
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001672:Biocompatible Materials / Q000494:pharmacology* / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D008855:Microscopy, Electron, Scanning; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects*; D009924:Organ Culture Techniques; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D011100:Polyglycolic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000648:ultrastructure; D013116:Spinal Cord / Q000166:cytology; D013266:Stilbamidines / Q000378:metabolism
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D001672:Biocompatible Materials; D009414:Nerve Growth Factors; D013266:Stilbamidines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Growth factors; Microspheres; Motor axons; Nerve conduit; Nerve regeneration; Sensory axons