Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair.
Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate-based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG+GFs), compared to SCI animals without biomaterial treatment.
Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.
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Grulova
Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.
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Slovinska
Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.
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Blaško
Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.|Laboratoire PRISM: Protéomique, Réponse Inflammatoire, Spectrométrie de Masse, INSERM U1192, Bât SN3, 1er étage, Université de Lille 1, F-59655 Villeneuve d'Ascq, France.
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Devaux
Laboratoire PRISM: Protéomique, Réponse Inflammatoire, Spectrométrie de Masse, INSERM U1192, Bât SN3, 1er étage, Université de Lille 1, F-59655 Villeneuve d'Ascq, France.
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Wisztorski
Laboratoire PRISM: Protéomique, Réponse Inflammatoire, Spectrométrie de Masse, INSERM U1192, Bât SN3, 1er étage, Université de Lille 1, F-59655 Villeneuve d'Ascq, France.
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Salzet
Laboratoire PRISM: Protéomique, Réponse Inflammatoire, Spectrométrie de Masse, INSERM U1192, Bât SN3, 1er étage, Université de Lille 1, F-59655 Villeneuve d'Ascq, France.
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Fournier
The Center of Regenerative Medicine and Stem Cell Research and The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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Kryukov
The Center of Regenerative Medicine and Stem Cell Research and The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.
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Cohen
Institute of Neurobiology, Center of Excellence for Brain Research, Department of Regenerative Medicine and Stem Cell Therapy, Slovak Academy of Sciences, Soltesovej 4-6, 040 01 Kosice, Slovakia.|Laboratoire PRISM: Protéomique, Réponse Inflammatoire, Spectrométrie de Masse, INSERM U1192, Bât SN3, 1er étage, Université de Lille 1, F-59655 Villeneuve d'Ascq, France.
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Cizkova
D000464:Alginates / Q000737:chemistry; D000818:Animals; D001369:Axons / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006930:Hyperalgesia; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D020543:Proteome; D040901:Proteomics / Q000379:methods; D051381:Rats; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation / Q000628:therapy; D013572:Synaptic Vesicles / Q000378:metabolism; D054457:Tissue Scaffolds
C100745:Aif1 protein, rat; D000464:Alginates; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D006603:Hexuronic Acids; D008840:Microfilament Proteins; D009414:Nerve Growth Factors; D020543:Proteome; D020723:Glucuronic Acid; D015740:Calcitonin Gene-Related Peptide