Tannic Acid Cross-linked Collagen Scaffolds and Their Anti-cancer Potential in a Tissue Engineered Breast Implant

Abstract

Tannic acid (TA) is a hydrolysable plant tannin, and it has been determined that TA functions as a collagen cross-linking agent through hydrogen-bonding mechanisms and hydrophobic effects. Since TA may have anti-tumor properties, it may be a viable cross-linking agent for collagen-based breast tissue scaffolds. The goal of this work was to determine if TA cross-linked scaffolds induce apoptotic processes in MCF-7 cancer cells, with minimal toxic effect on healthy D1 mesenchymal stem-like stromal cells. Cross-linked collagen scaffolds that were uniform, easily reproduced, easily characterized, and readily used in cell culture were manufactured. Thermal denaturation temperatures of the cross-linked scaffolds (68°C) were shown to be significantly higher when compared to those of uncross-linked scaffolds (55°C). Scanning electron microscopy images demonstrated the replacement of irregular collagen fibers with sheet-like structures upon cross-linking. The cross-linking solution concentration of TA that appears to be best for inducing apoptotic processes in MCF-7 cells, while minimizing toxic effect on D1 cells, is 1 mg/ml. At this concentration, the MCF-7 cell metabolic activity did not change over a 72-h period (i.e., proliferation was limited) while there was an increase in metabolic activity of D1 cells over the 72-h period. TA did appear to inhibit the production of lipid by D1 cells cultured in an adipogenic cocktail; in the future, the rate and duration of inhibition could be tailored to allow gradual bulking of the implant. The results suggest that the level of TA cross-linking can be modulated to provide optimal use in a tissue engineering composite.