title: Thermally-triggered gelation of PLGA dispersions: towards an injectable colloidal cell delivery system.
abstract: In this study the properties of poly(D,L-lactide-co-glycolide) (PLGA) dispersions containing a thermoresponsive cationic copolymer were investigated. The PLGA dispersions were prepared by interfacial deposition in aqueous solution and were rendered thermoresponsive by addition of a cationic poly(N-isopropyl acrylamide) (PNIPAm) graft copolymer. The copolymers used had the general composition PDMA(x)(+)-g-(PNIPAm(n))(y). DMA(+) is quarternarized N,N-dimethylaminoethyl methacrylate. The PDMA(x)(+)-g-(PNIPAm(n))(y) copolymers have x and y values that originate from the macroinitiator used for their preparation; values for n correspond to the PNIPAm arm length. The thermoresponsive dispersions were characterised using photon correlation spectroscopy, turbidity measurements and electrophoretic mobility measurements. A strong electrostatic attraction between the anionic PLGA particles and cationic copolymer was present and the dispersions showed thermally-triggered gelation at total polymer volume fractions as low as 0.015. These new PLGA gels, which formed at about 32 degrees C, had elastic modulus values that could be controlled using dispersion composition. Scanning electron micrographs of the gels showed high porosity and interconnectivity of elongated pores. Remarkably, the gels were flexible and had critical yield strains as high as 160%. The ability of the gels to support growth of bovine nucleus pulposus cells was investigated using two-dimensional cell culture. The cells proliferated and remained viable on the gels after 3days. The results suggest that this general family of biodegradable thermogelling PLGA dispersions, introduced here for the first time, may have longer-term application as an injectable colloidal cell delivery system.
authors.affiliation: Biomaterial Science Group, School of Materials, The University of Manchester, Grosvenor Street, Manchester M17HS, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Fraylich
authors.forename: Ruixue
authors.initials: R
authors.lastname: Liu
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richardson
authors.forename: Pauline
authors.initials: P
authors.lastname: Baird
authors.forename: Judith
authors.initials: J
authors.lastname: Hoyland
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Freemont
authors.forename: Cameron
authors.initials: C
authors.lastname: Alexander
authors.forename: Kevin
authors.initials: K
authors.lastname: Shakesheff
authors.forename: Francesco
authors.initials: F
authors.lastname: Cellesi
authors.forename: Brian R
authors.initials: BR
authors.lastname: Saunders
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000180:Acrylic Resins; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D003102:Colloids / Q000737:chemistry*; D005782:Gels / Q000737:chemistry*; D007267:Injections; D007403:Intervertebral Disc / Q000166:cytology; D019344:Lactic Acid / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013696:Temperature; D023822:Tissue Engineering
chemical_list: D000178:Acrylamides; D000180:Acrylic Resins; D001672:Biocompatible Materials; D003102:Colloids; D005782:Gels; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C052970:poly-N-isopropylacrylamide; D011100:Polyglycolic Acid; D019344:Lactic Acid