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 four weeks. Viable cells implanted within the device could be identified after two 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.

Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid) electrospun fibrous scaffold for bone regeneration

“…It is believed that the enhancement of the scaffold surface area may promote cell growth more efficiently than a bulk substrate. 50 Similar results were observed in other studies showing that addition of MBG into the polymer matrix enhanced cell spreading and proliferation. 43,51 Altogether, these data leave little doubt that MBG possesses excellent in vitro bioactivity.…”

Overcoming foreign-body reaction through nanotopography: Biocompatibility and immunoisolation properties of a nanofibrous membrane

“…In comparison, plastics-based macroencapsulation devices represent a more practical or translatable strategy for developing robust products for cell transplantation [3]. However, the choice of biocompatible and porous materials is so far limited, despite the fact that polytetrafluoroethylene (PTFE) [9,37] and acrylic copolymer-based membranes [4] have been fabricated with precise pore sizes and selective permeability [38].…”

Prevascularized silicon membranes for the enhancement of transport to implanted medical devices

“…Vascularization of porous matrices for interfacing the blood supply to an underlying foreign body has been pursued for 20 years with limited success. One key limit to existing approaches may be the largely random pore structure of expanded or electrospun polymer matrices. Electrospun nonwoven mats do not have pores in the traditional sense, but simply void space of undefined shape and widely varying characteristic width around randomly arrayed fibers.…”