title: Novel "breath figure"-based synthetic PLGA matrices for in vitro modeling of mammary morphogenesis and assessing chemotherapeutic response.
abstract: Biodegradable poly(lactic-co-glycolic acid) (PLGA) porous films are developed to support mammary cell growth and function. Such porous polymer matrices of PLGA are generated using the easily implemented water-templating "breath-figure" technique that allows water droplets to penetrate the nascent polymer films to create a rough porous polymer film. Such breath figure-based micropatterned porous films show higher epithelial differentiation and growth than the corresponding flat 2D films, and represent the first instance of using them for tissue culture. Specifically, the breath figure morphology supports robust acinar growth with almost double the number of lobular-alveolar units compared to the 2D cultures. Gene profile analysis indicates that the cells grown on porous polymer films show enhanced expressions of mammary differentiation genes (GATA3, EMA, and INTEGB4) but lower the expression of mesenchymal gene (CALLA). Hormonal stimulation of these cultures dramatically increases expression of progenitor marker gene Notch1. Importantly, cells grown on porous PLGA films exhibit an enhanced resistance to doxorubicin treatment in comparison to 2D cultures. Breath-figure PLGA films show promise in mimicking in vivo mammary functions and can potentially be used to screen chemotherapeutic drugs. The simplicity and ease of fabrication of these polymer films is especially appealing to the development of effective biomaterials to support cell culture and differentiation.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Tulane University, New Orleans, LA, 70118, USA.
authors.forename: Thiruselvam
authors.initials: T
authors.lastname: Ponnusamy
authors.forename: Geetika
authors.initials: G
authors.lastname: Chakravarty
authors.forename: Debasis
authors.initials: D
authors.lastname: Mondal
authors.forename: Vijay T
authors.initials: VT
authors.lastname: John
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D061986:MCF-7 Cells; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development*; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA; breath figures; honeycomb structures; mammary morphogenesis; porous polymer films