Novel "Breath Figure"‐Based Synthetic PLGA Matrices for In Vitro Modeling of Mammary Morphogenesis and Assessing Chemotherapeutic Response. Issue 5 (17th October 2013)

• Record Type: Journal Article
• Authors: Ponnusamy, Thiruselvam; Chakravarty, Geetika; Mondal, Debasis; John, Vijay T.
• Is Part Of: Advanced healthcare materials. Volume 3:Issue 5(2014:May)
• Page Start: 703
• Page End: 713
• Publication Date: 2013-10-17
• Subjects: breath figures -- honeycomb structures -- PLGA -- porous polymer films -- mammary morphogenesis; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201300184
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : Breath figure porous poly(lactic‐co‐glycolic acid) (PLGA) films with relatively large porous matrices provide a conducive environment for mammary cells to steer the growth of epithelia in a stereotyped pattern to form ducts and lumini. Drug sensitivity studies carried out on breast cancer cells cultured in the physiologically relevant microenvironment of these films indicate their use as alternative biomaterials for tissue engineering and screening of anti‐cancer drugs.