title: A naonoporous cell-therapy device with controllable biodegradation for long-term drug release.
abstract: Herein we describe the development and implementation of a nanoporous cell-therapy device with controllable biodegradation. Dopamine-secreting PC12 cells were housed within newly formulated alginate-glutamine degradable polylysine (A-GD-PLL) microcapsules. The A-GD-PLL microcapsules provided a 3-D microenvironment for good spatial cell growth, viability and proliferation. The microcapsules were subsequently placed within a poly(ethylene glycol) (PEG)-coated poly(ε-caprolactone) (PCL) chamber covered with a PEG-grafted PCL nanoporous membrane formed by phase inversion. To enhance PC12 cell growth and to assist in controlled degradation of both the PC12 cells and the device construct, small PCL capsules containing neural growth factor (PCL-NGF) and a poly(lactic-co-glycolic acid) pellet containing glutamine (PLGA-GLN) were also placed within the PCL chamber. Release of NGF from the PCL-NGF capsules facilitated cell proliferation and viability, while the controlled release of GLN from the PLGA-GLN pellet resulted in A-GD-PLL microcapsule degradation and eventual PC12 cell death following a pre-specified period of time (4 weeks in this study). In vivo, our device was found to be well tolerated and we successfully demonstrated the controlled release of dopamine over a period of four weeks. This integrated biodegradable device holds great promise for the future treatment of a variety of diseases.
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: He
authors.forename: Eric
authors.initials: E
authors.lastname: Luedke
authors.forename: Xulang
authors.initials: X
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Alessandra
authors.initials: A
authors.lastname: Schmitt
authors.forename: Ben
authors.initials: B
authors.lastname: McClarren
authors.forename: Valerie
authors.initials: V
authors.lastname: Grignol
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D017690:Cell Transplantation / Q000295:instrumentation*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004298:Dopamine / Q000008:administration & dosage* / Q000737:chemistry; D004867:Equipment Design; D020723:Glucuronic Acid / Q000737:chemistry; D005973:Glutamine / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000737:chemistry; D016716:PC12 Cells; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000737:chemistry; D016062:Porosity; D051381:Rats
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D005973:Glutamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid; D020932:Nerve Growth Factor; D004298:Dopamine