title: Novel high-viscosity polyacrylamidated chitosan for neural tissue engineering: fabrication of anisotropic neurodurable scaffold via molecular disposition of persulfate-mediated polymer slicing and complexation.
abstract: Macroporous polyacrylamide-grafted-chitosan scaffolds for neural tissue engineering were fabricated with varied synthetic and viscosity profiles. A novel approach and mechanism was utilized for polyacrylamide grafting onto chitosan using potassium persulfate (KPS) mediated degradation of both polymers under a thermally controlled environment. Commercially available high molecular mass polyacrylamide was used instead of the acrylamide monomer for graft copolymerization. This grafting strategy yielded an enhanced grafting efficiency (GE = 92%), grafting ratio (GR = 263%), intrinsic viscosity (IV = 5.231 dL/g) and viscometric average molecular mass (MW = 1.63 × 106 Da) compared with known acrylamide that has a GE = 83%, GR = 178%, IV = 3.901 dL/g  and MW = 1.22 × 106 Da. Image processing analysis of SEM images of the newly grafted neurodurable scaffold was undertaken based on the polymer-pore threshold. Attenuated Total Reflectance-FTIR spectral analyses in conjugation with DSC were used for the characterization and comparison of the newly grafted copolymers. Static Lattice Atomistic Simulations were employed to investigate and elucidate the copolymeric assembly and reaction mechanism by exploring the spatial disposition of chitosan and polyacrylamide with respect to the reactional profile of potassium persulfate. Interestingly, potassium persulfate, a peroxide, was found to play a dual role initially degrading the polymers-"polymer slicing"-thereby initiating the formation of free radicals and subsequently leading to synthesis of the high molecular mass polyacrylamide-grafted-chitosan (PAAm-g-CHT)-"polymer complexation". Furthermore, the applicability of the uniquely grafted scaffold for neural tissue engineering was evaluated via PC12 neuronal cell seeding. The novel PAAm-g-CHT exhibited superior neurocompatibility in terms of cell infiltration owing to the anisotropic porous architecture, high molecular mass mediated robustness, superior hydrophilicity as well as surface charge due to the acrylic chains. Additionally, these results suggested that the porous PAAm-g-CHT scaffold may act as a potential neural cell carrier.
authors.affiliation: Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa. viness.pillay@wits.ac.za.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Girish
authors.initials: G
authors.lastname: Modi
authors.forename: Dinesh
authors.initials: D
authors.lastname: Naidoo
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008970:Molecular Weight; D009416:Nerve Regeneration; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D017680:Potassium Compounds / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry; D013816:Thermodynamics; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014783:Viscosity; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D048271:Chitosan; D011108:Polymers; D017680:Potassium Compounds; D013431:Sulfates; D000099166:Polyacrylamides; C009007:potassium persulfate