title: Strategies for neurotrophin-3 and chondroitinase ABC release from freeze-cast chitosan-alginate nerve-guidance scaffolds.
abstract: Freeze casting, or controlled unidirectional solidification, can be used to fabricate chitosan-alginate (C-A) scaffolds with highly aligned porosity that are suitable for use as nerve-guidance channels. To augment the guidance of growth across a spinal cord injury lesion, these scaffolds are now evaluated in vitro to assess their ability to release neurotrophin-3 (NT-3) and chondroitinase ABC (chABC) in a controlled manner. Protein-loaded microcapsules were incorporated into C-A scaffolds prior to freeze casting without affecting the original scaffold architecture. In vitro protein release was not significantly different when comparing protein loaded directly into the scaffolds with release from scaffolds containing incorporated microcapsules. NT-3 was released from the C-A scaffolds for 8 weeks in vitro, while chABC was released for up to 7 weeks. Low total percentages of protein released from the scaffolds over this time period were attributed to limitation of diffusion by the interpenetrating polymer network matrix of the scaffold walls. NT-3 and chABC released from the scaffolds retained bioactivity, as determined by a neurite outgrowth assay, and the promotion of neurite growth across an inhibitory barrier of chondroitin sulphate proteoglycans. This demonstrates the potential of these multifunctional scaffolds for enhancing axonal regeneration through growth-inhibiting glial scars via the sustained release of chABC and NT-3. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Francis
authors.affiliation: Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA.|Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Hunger
authors.affiliation: Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA.
authors.forename: Amalie E
authors.initials: AE
authors.lastname: Donius
authors.affiliation: Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH, 03755, USA.
authors.forename: Ulrike G K
authors.initials: UG
authors.lastname: Wegst
authors.affiliation: School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Wheatley
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001369:Axons / Q000473:pathology; D048271:Chitosan / Q000737:chemistry; D019765:Chondroitin ABC Lyase / Q000378:metabolism*; D004339:Drug Compounding; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000502:physiology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000628:therapy; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020933:Neurotrophin 3; D011108:Polymers; D020723:Glucuronic Acid; D048271:Chitosan; D019765:Chondroitin ABC Lyase
keywords: chitosan-alginate scaffold; chondroitinase ABC; freeze casting; microcapsule; neurotrophin-3; spinal cord injury