Rational Fabrication of Functionally-Graded Surfaces for Biological and Biomedical Applications

Abstract

As a ubiquitous feature of the biological world, gradation, in either composition or structure, is essential to many functions and processes. Taking protein gradation as an example, it plays a pivotal role in the development and evolution of human bodies, including stimulation and direction of the outgrowth of peripheral nerves in a developing fetus. It is also critically involved in wound healing by attracting and guiding immune cells to the site of injury or infection. Another good example can be found in the tendon-to-bone enthesis that relies on gradations in composition, structure, and cell phenotype to create a gradual change in mechanical stiffness. It is these unique gradations that eliminate the high level of stress at the interface, enabling the effective transfer of mechanical load from tendon to bone. How to fabricate and utilize graded surfaces and materials has been a constant theme of research in the context of materials science, chemistry, cell biology, and biomedical engineering. In cell biology, for example, graded surfaces are employed to investigate the fundamental mechanisms related to embryo development and to elucidate cell behaviors under chemo-, hapto-, or mechano-taxis. Scaffolds based upon graded materials have also been widely explored to enhance tissue repair or regeneration by accelerating cell migration and/or controlling stem cell differentiation. In this Account, we review our efforts in the fabrication and utilization of functionally graded surfaces. The gradation typically occurs as gradual changes in terms of composition, structure (e.g., pore size or fiber alignment), and/or coverage density of molecular species or larger objects such as particles and cells. Specifically, we focus on two strategies for generating various types of gradations along the surface of a substrate. In the first strategy, the substrate is vertically placed in a container, followed by the addition of a solution containing the functional component at a constant rate. Owing to the variations in contact time, the amount of the component deposited on the substrate naturally takes a gradual change along the vertical direction. In the second strategy, a moving collector or mask is used to control the amount of the component deposited on a substrate during jet printing or electrospray. As for applications, we highlight the following examples: (i) promotion of neurite outgrowth for peripheral nerve repair; (ii) acceleration of cell migration for wound closure; and (iii) mimicking of the structure and/or force transition at the tendon-to-bone enthesis for interfacial tissue engineering. The surface gradation can be presented in a uniaxial or radial fashion, and further integrated with the structural features on the underlying substrate to suit a specific application. In addition to general issues such as diversity of the surface gradation and reproducibility of the fabrication method, we also offer perspectives on new directions for future development. The systems and strategies discussed in this Account are expected to open the door to a range of fundamental inquires while enabling various biological and biomedical applications.