Evaluating chemotherapeutic response in breast cancer

by | Apr 24, 2014

The need to develop biocompatible and biodegradable materials has intensified as the fields of bioengineering and regenerative medicine come of age.

The need to develop biocompatible and biodegradable materials has intensified as the fields of bioengineering and regenerative medicine come of age. Great emphasis is being placed on developing biomaterials that can mimic cell matrix interactions that sculpt tissues during organogenesis. Understanding the complex interplay operative during organogenesis is paramount to discern how loss of these interactions results in cancer and to utilize the knowledge gained in screening for anti-cancer compounds.

Mammary morphogenesis is an excellent model system to understand how cell matrix interactions influence mammary development and how loss of this regulation results in breast cancer. However, the lack of appropriate biomaterials that can recapitulate the in vivo environment of breast tissue poses a significant challenge in capturing the process in vitro.  The lack of necessary stiffness required to support ductal morphogenesis, batch to batch variations in the composition of the extracellular matrix, differences in the number and quantity of growth factors etc. have all necessitated the development of alternative biomaterials.

The FDA approved poly (lactic-co-glycolic acid) (PLGA)  has found acceptance in tissue culture applications as it is a readily available biodegradable synthetic material with low cost of production  and no toxicity. PLGA can be easily engineered to create micro-patterned films using a simple evaporation method whereby a water immiscible polymer solution of PLGA is rapidly evaporated in the presence of high humidity to give rise to honeycomb structured porous films. The process is similar to the exhaled condensation of water droplets on a cold surface; hence the process is also referred as the “breath figure” technique and the resultant films as breath figure films.

The paper by Ponnusamy and coworkers describes the use of PLGA to create micro-patterned breath figure films using either the spin or dip coating techniques.  Breast cancer cells cultured on these patterned films are significantly more differentiated compared to cells grown on flat surfaces. There is clear evidence of functional growth as evidenced by development of branched ductal and lobular alveolar structures and accompanying changes in gene expression.  These findings suggest that such engineered PLGA films may be an effective and alternative biomaterial to recapitulate the branching morphogenesis seen in in-vivo model systems of normal breast epithelial cells and to develop drug screening protocols against breast cancer cells. The ease of fabricating such structures is the primary driving force to further this research.

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