Advancing Cell-on-a-Chip Interfaces with Bio-functional Terpolymer Nano-Brushes Exhibiting Strong Resistance to Bacterial Adhesion

Introduction:

Bioengineering plays a crucial role in developing advanced biomedical devices and interfaces that integrate biological systems. One major challenge in the development of cell-on-a-chip interfaces is preventing bacterial contamination while maintaining cellular compatibility. Low-fouling (super-)hydrophilic zwitterionic polymer materials have emerged as potential biomedical materials and bio-functional coatings. Here, we report a novel terpolymer nano-brush coating that effectively suppresses undesired biomolecular fouling and biofilm formation while providing sufficient molecular functionalization capacity..

Methods

A terpolymer brush nanolayer composed of carboxybetaine methacrylamide (CBMAA), N-(2-hydroxypropyl) methacrylamide (HPMAA), and sulfobetaine methacrylamide (SBMAA) was synthesized on glass and gold-coated glass substrates using the ATRP method. The chemical structure, thickness, surface zeta potential, fouling resistance, and wettability of this coating were analyzed using XPS, FT-IRRAS, spectroscopic ellipsometry, electrokinetic analyzer, SPR, and water contact angle measurements. Bacterial and cell adhesion studies were conducted on bare and RGD-functionalized terpolymer brushes.

Results

In vitro analyses confirmed the coating’s exceptional resistance against Staphylococcus epidermidis and Pseudomonas aeruginosa while enhancing macrophage mobility compared to uncoated glass, likely due to the coating’s highly hydrated nature and low protein adsorption. RGD-functionalized terpolymer coatings were found to be non-cytotoxic for SaOS-2 osteosarcoma cells, promoting cell adhesion and spreading without significantly increasing bacterial adhesion or protein adsorption. These results demonstrate that bio-functional terpolymer nano-brushes provide a dual benefit of bacterial resistance and cellular compatibility, making them highly prospective for cell-on-a-chip applications.

Discussion

This study discusses the importance of combining antifouling efficacy, enhanced cellular interaction, and non-cytotoxicity when developing tailored materials for next-generation cell-on-a-chip interfaces. Future research will focus on scaling up the synthesis process and exploring the long-term stability and biocompatibility of these nano-brushes in various bioengineering applications.