Microfluidic synthesis of composite cross-gradient materials for investigating cell-biomaterial interactions

Combinatorial material synthesis is a powerful approach for creating composite material libraries for the high-throughput screening of cell-material interactions. Although current combinatorial screening platforms have been tremendously successful in identifying target (termed "hit") materials from composite material libraries, new material synthesis approaches are needed to further optimize the concentrations and blending ratios of the component materials. Here we employed a microfluidic platform to rapidly synthesize composite materials containing cross-gradients of gelatin and chitosan for investigating cell-biomaterial interactions. The microfluidic synthesis of the cross-gradient was optimized experimentally and theoretically to produce quantitatively controllable variations in the concentrations and blending ratios of the two components. The anisotropic chemical compositions of the gelatin/chitosan cross-gradients were characterized by Fourier transform infrared spectrometry and X-ray photoelectron spectrometry. The three-dimensional (3D) porous gelatin/chitosan cross-gradient materials were shown to regulate the cellular morphology and proliferation of smooth muscle cells (SMCs) in a gradient-dependent manner. We envision that our microfluidic cross-gradient platform may accelerate the material development processes involved in a wide range of biomedical applications.