title: Vascularization and cellular isolation potential of a novel electrospun cell delivery vehicle.
abstract: A clinical need exists for a cell delivery device that supports long-term cell viability, cell retention within the device and retrieval of delivered cells if necessary. Previously, cell isolation devices have been based on hollow fiber membranes, porous polymer scaffolds, alginate systems, or micro-machined membranes. We present the development and characterization of a novel dual porosity electrospun membrane based device, which supports cellular infiltration and vascularization of its outer porous layer and maintains cellular isolation within a lumen bounded by an inner low porosity layer. Electrospinning conditions were initially established to support electrospun fiber deposition onto nonconductive silicone surfaces. With these parameters established, devices for in vivo evaluations were produced using nylon as a nonconductive scaffold for deposition of dual porosity electrospun fibers. The outer porous layer supported the development of a penetrating microcirculation and the membrane supported the transfer of insulin from encapsulated sustained release pellets for 4 weeks. Viable cells implanted within the device could be identified after 2 weeks of implantation. Through the successful demonstration of survival and cellular isolation of human epithelial cells within the implanted devices and the ability to use the device to deliver insulin, we have established the utility of this device toward localized cell transplantation. The cell delivery device establishes a platform to test the feasibility of approaches to cell dose control and cell localization at the site of implantation in the clinical use of modified autologous or allogeneic cells.
authors.affiliation: Cardiovascular Innovation Institute, University of Louisville and Jewish Hospital, Louisville, Kentucky, 40202.
authors.forename: Laxminarayanan
authors.initials: L
authors.lastname: Krishnan
authors.forename: Jeremy
authors.initials: J
authors.lastname: Touroo
authors.forename: Robert
authors.initials: R
authors.lastname: Reed
authors.forename: Eugene
authors.initials: E
authors.lastname: Boland
authors.forename: James B
authors.initials: JB
authors.lastname: Hoying
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Williams
mesh_terms: D001672:Biocompatible Materials; D001808:Blood Vessels / Q000254:growth & development*; D002469:Cell Separation; D004058:Diffusion; D007328:Insulin / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D007328:Insulin
keywords: cellular isolation; electrospinning; neovascularization; porosity; vascularized cell delivery
references.citation: J Biomed Mater Res A. 2006 Jul;78(1):59-65
references.pmid: 16602088
references.citation: Transplant Proc. 2011 Nov;43(9):3256-61
references.pmid: 22099770
references.citation: Tissue Eng. 1996 Winter;2(4):289-98
references.pmid: 19877960
references.citation: Adv Drug Deliv Rev. 1998 Aug 3;33(1-2):87-109
references.pmid: 10837655
references.citation: Nat Biotechnol. 1997 Apr;15(4):358-62
references.pmid: 9094138
references.citation: Tissue Eng. 2005 Jan-Feb;11(1-2):257-66
references.pmid: 15738680
references.citation: Transplant Proc. 1992 Dec;24(6):2924
references.pmid: 1281580
references.citation: Biomaterials. 1996 Feb;17(3):257-66
references.pmid: 8745322
references.citation: Biotechnol Bioeng. 1993 Sep 5;42(6):716-23
references.pmid: 18613104
references.citation: J Biomed Mater Res A. 2010 Dec 1;95(3):811-8
references.pmid: 20734331
references.citation: Tissue Eng Part A. 2011 Mar;17(5-6):841-53
references.pmid: 20973748
references.citation: Biomed Microdevices. 2009 Feb;11(1):297-312
references.pmid: 18987977
references.citation: ASAIO J. 2009 Jul-Aug;55(4):400-5
references.pmid: 19506465
references.citation: J Hepatobiliary Pancreat Surg. 2000;7(4):374-9
references.pmid: 11180858
references.citation: J Biomed Mater Res A. 2009 Oct;91(1):231-40
references.pmid: 18814222
references.citation: Tissue Eng Part A. 2009 Jun;15(6):1363-71
references.pmid: 18976155
references.citation: Biomed Microdevices. 1999;1(2):131-8
references.pmid: 16281113
references.citation: J Biomed Mater Res A. 2011 Oct;99(1):67-73
references.pmid: 21800416
references.citation: J Biomed Mater Res. 1995 Dec;29(12):1517-24
references.pmid: 8600142
references.citation: Biointerphases. 2012 Dec;7(1-4):13
references.pmid: 22589056
references.citation: Cardiovasc Pathol. 1999 Mar-Apr;8(2):63-71
references.pmid: 10724503