Functionally Graded Surfaces and Materials: From Fabrication to Biomedical Applications.

Functionally graded surfaces and materials, featuring spatial variations in terms of composition, structure, and other properties across distance, have emerged as powerful platforms for mimicking native tissue architectures and enabling a wide range of biomedical applications. This review aims to provide a comprehensive overview of their fabrication methods and biomedical applications. We begin by introducing the concept of gradients and their inherent biological relevance in nature. With a distinct focus on either surfaces or materials, we then discuss the fabrication methods and characterization techniques capable of controlling the graded profiles. Importantly, representative examples are provided to highlight how engineered gradients regulate specific cellular responses and functionalities in biomedical contexts. Despite significant progress, challenges remain in translating laboratory-scale fabrication to clinical use, such as ensuring good reproducibility and scalability. At the end, we discuss how computational modeling and artificial intelligence offer new opportunities to address these challenges. We hope this review provides a framework for advancing the development of next-generation functionally graded surfaces and materials toward diverse biomedical applications.