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PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance
Camilla Carbone1, Salvatrice Rigogliuso2, Valerio Maria Bartolo Brucato1
1Engineering Department, University of Palermo, Palermo, Italy.
Journal of Biomedical Materials Research. Part A
|November 16, 2024
Summary
Three-dimensional (3D) breast cancer models using poly-l-lactic-acid scaffolds show increased chemoresistance compared to 2D cultures. These biomimetic models better represent drug response, aiding research into multidrug resistance and treatment failure.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Materials Science
Background:
- Multidrug resistance (MDR) in breast cancer is a significant obstacle to effective treatment.
- Traditional 2D cell cultures do not fully recapitulate the complex tumor microenvironment, limiting their predictive power for drug response.
- Sophisticated 3D models are needed to better understand MDR mechanisms and develop improved therapeutic strategies.
Purpose of the Study:
- To develop and evaluate poly-l-lactic-acid (PLLA) porous scaffolds as 3D models for breast cancer research.
- To compare the chemoresistance of breast cancer cell lines (MDA-MB-231, MCF-7, MCF-7R) in 3D scaffolds versus traditional 2D cultures when treated with doxorubicin.
- To investigate the influence of 3D architecture on cellular morphology and drug response.
Main Methods:
- Porous PLLA scaffolds were fabricated using thermally induced phase separation.
- Breast cancer cell lines (MDA-MB-231, MCF-7, MCF-7R) were cultured in 2D and on PLLA 3D scaffolds.
- The MTS assay was employed to determine half-maximal inhibitory concentration (IC50) values after doxorubicin treatment in both 2D and 3D cultures.
- Cellular morphology was analyzed post-treatment.
Main Results:
- IC50 values for doxorubicin were significantly higher in 3D cultures across all cell lines compared to 2D cultures.
- MCF-7R cells, a multidrug-resistant variant, exhibited enhanced resistance in 3D models, with IC50 values reached only after 6 days of treatment.
- Cellular morphology changes were observed in 3D cultures post-treatment, with MDA-MB-231 cells losing clustered structure and MCF-7/MCF-7R cells showing disrupted layers.
- All tested cell lines demonstrated increased chemoresistance in the 3D scaffold environment, indicating a more biomimetic response.
Conclusions:
- Polymeric 3D scaffolds provide a more accurate and biomimetic platform for studying breast cancer chemoresistance.
- The 3D scaffold model effectively enhances the observed drug resistance, particularly in multidrug-resistant cell lines.
- These findings highlight the potential of PLLA 3D scaffolds as an intermediate model between 2D cultures and animal studies for breast cancer research and drug development.
