This article systematically reviews advanced fabrication strategies for functionally graded surfaces and materials and their broad applications in tissue engineering, neural regeneration, and drug screening, emphasizing the future potential of bio-inspired design and AI-driven manufacturing.
Literature Overview
This review, titled 'Functionally Graded Surfaces and Materials: From Fabrication to Biomedical Applications' and published in Chemical Reviews, summarizes advanced fabrication methods for surfaces and materials with spatially varying composition, structure, and properties, along with their diverse biomedical applications. The article systematically introduces the concept of gradients and their biological relevance in nature, elaborates on various manufacturing and characterization techniques for surface and material gradients, and demonstrates through representative examples how gradient structures regulate cell behavior. The authors also discuss the challenges of reproducibility and scalability in translating laboratory fabrication to clinical applications, and highlight emerging opportunities in computational modeling and artificial intelligence for optimizing gradient design and manufacturing. The entire section is coherent and logically structured, ending with a Chinese period.Background Knowledge
Functionally graded materials (FGMs) are a class of advanced materials with spatially graded structures or compositions, inspired by heterogeneous structures widely found in nature, such as the tendon-bone interface, teeth, and the ocular lens. These natural structures achieve efficient mechanical load transfer and biological functional integration across different tissues through continuous transitions in composition, structure, and mechanical properties, thereby avoiding stress concentration and interfacial failure. In biomedical engineering, conventional homogeneous materials often fail to meet the multifaceted requirements at complex tissue interfaces—for instance, the tendon-bone junction requires a smooth stiffness transition from high to low. Thus, constructing material systems with spatial gradients has become a key direction in biomimetic design. In recent years, research has focused on developing controllable and reproducible gradient manufacturing techniques, including physical deposition, electrospinning, 3D printing, microfluidics, and photolithography. However, challenges remain in achieving high-precision, multi-scale, and multi-gradient coupled complex structures. Moreover, while gradient materials show great potential in tissue engineering scaffolds, neural regeneration conduits, vascular grafts, and drug delivery systems, their long-term stability, biocompatibility, and feasibility for large-scale production require systematic evaluation. This review provides a systematic framework for the development of next-generation functionally graded materials, advancing their translation toward clinical applications.
Research Methods and Experiments
The article systematically reviews various fabrication strategies for functionally graded surfaces and materials. For gradient surfaces, it highlights progressive immersion, mask-assisted, field-induced, and microfluidic-assisted deposition methods. Progressive immersion controls the immersion speed or duration of substrates in reactive solutions to achieve linear or radial gradients in composition or density; mask-assisted techniques combine electrospray or UV lithography with masks to regulate particle deposition or crosslinking degree, forming high-resolution gradient patterns; field-induced methods use magnetic, electric, or thermal fields to drive directional particle migration, enabling non-contact gradient construction; microfluidics precisely controls spatial gradients by manipulating reactant concentrations through multi-channel flows.
For functionally graded materials, the article summarizes diffusion-driven, force-driven, and layer-by-layer assembly methods. Diffusion-based techniques form compositional gradients via molecular or thermal diffusion; force-driven approaches—such as gravity, centrifugal, electrostatic, and magnetic forces—regulate particle distribution; layer-by-layer assembly includes casting, coating, electrospinning, and 3D printing, enabling the construction of three-dimensional gradient structures. Notably, 3D printing allows for complex, multi-material, and multi-scale gradient designs.Key Conclusions and Perspectives
Research Significance and Prospects
This review offers systematic guidance for the rational design and fabrication of functionally graded materials, emphasizing the importance of interdisciplinary approaches in biomaterial development. By integrating materials science, bioengineering, and computational technologies, more complex and biomimetic gradient structures can be achieved, advancing tissue engineering and regenerative medicine.
The article notes that although various gradient fabrication techniques have been developed in laboratories, their clinical translation is hindered by issues of reproducibility and scalability. Therefore, developing standardized and automated manufacturing processes is a key future direction. Additionally, the design of coupled multi-gradients (e.g., chemical-mechanical-electrical) will further enhance material functionality.
The integration of artificial intelligence and machine learning opens new avenues for gradient optimization. By training models to predict gradient-property relationships, material screening and design can be accelerated, reducing experimental costs. Combined with high-throughput experimentation and digital twin technologies, closed-loop intelligent manufacturing may become possible, facilitating the industrial application of gradient materials.
Conclusion
This article provides a comprehensive review of fabrication methods for functionally graded surfaces and materials and their progress in biomedical applications. Gradient structures, inspired by nature, enable efficient integration and functional optimization across tissues through spatial variations in composition, structure, and properties. The article systematically summarizes surface gradient fabrication techniques such as progressive immersion, mask-assisted, field-induced, and microfluidic methods, as well as bulk gradient material fabrication strategies including diffusion, force-driven, and 3D printing approaches. These methods have been successfully applied in tissue engineering scaffolds, neural regeneration conduits, and drug screening platforms, demonstrating excellent biocompatibility and functional regulation capabilities. However, laboratory-scale fabrication still faces challenges in reproducibility, resolution, and scalability. In the future, integrating computational modeling and artificial intelligence may enable intelligent and automated gradient design, promoting widespread clinical applications in regenerative medicine. This review offers a theoretical foundation and technical roadmap for the development of next-generation functionally graded materials, providing significant guidance.
