A paradigm for high-throughput screening of cell-selective surfaces coupling orthogonal gradients and machine learning-based cell recognition

Hongye Hao; Yunfan Xue; Yuhui Wu; Cong Wang; Yifeng Chen; Xingwang Wang; Peng Zhang; Jian Ji

doi:10.1016/j.bioactmat.2023.04.022

A paradigm for high-throughput screening of cell-selective surfaces coupling orthogonal gradients and machine learning-based cell recognition

Bioact Mater. 2023 May 5:28:1-11. doi: 10.1016/j.bioactmat.2023.04.022. eCollection 2023 Oct.

Authors

Hongye Hao^{1

2}, Yunfan Xue^{1

2}, Yuhui Wu^{1

2}, Cong Wang^{1

2}, Yifeng Chen^{1

2}, Xingwang Wang^{1

2}, Peng Zhang^{1

2}, Jian Ji^{1

2}

Affiliations

¹ MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, PR China.
² International Research Center for X Polymers, International Campus, Zhejiang University, Haining, 314400, PR China.

Abstract

The combinational density of immobilized functional molecules on biomaterial surfaces directs cell behaviors. However, limited by the low efficiency of traditional low-throughput experimental methods, investigation and optimization of the combinational density remain daunting challenges. Herein, we report a high-throughput screening set-up to study biomaterial surface functionalization by integrating photo-controlled thiol-ene surface chemistry and machine learning-based label-free cell identification and statistics. Through such a strategy, a specific surface combinational density of polyethylene glycol (PEG) and arginine-glutamic acid-aspartic acid-valine peptide (REDV) leads to high endothelial cell (EC) selectivity against smooth muscle cell (SMC) was identified. The composition was translated as a coating formula to modify medical nickel-titanium alloy surfaces, which was then proved to improve EC competitiveness and induce endothelialization. This work provided a high-throughput method to investigate behaviors of co-cultured cells on biomaterial surfaces modified with combinatorial functional molecules.