Biomimetic Interfaces in Biomedical Devices
Authors: João F. Mano, Insung S. Choi, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2017)

The general performance of biomedical devices is dictated by the interaction between material surfaces and the biological environment. Interfaces regulate important aspects at the biological and physicochemical level, and may be controlled by using bio-inspired principles, such as by modification of the chemical nature of the biomaterial, by exposure of biochemical signals, or by design of special physical/topological features. Recent efforts have permitted remarkable developments in the design of interfaces, not only to enhance the performance of conventional implants, but also to fabricate more advanced biomedical devices, such as hybrid structures or biomaterials for regenerative medicine, smart delivery systems, and biosensors (Scheme 1). This special issue results from the generous and high-quality contributions of world-leading researchers in topics exploring the science and engineering of biomimetic interfaces that tune important properties, such as spatio-temporally controlled cell-cell or cell-surface interactions, bacterial response, molecular recognition, adhesiveness and wettability, adaptability and response to external stimuli, self-assembly, and protein adsorption/reorganization. Cell biology knowledge has enabled the recognition of essential qualities that should be incorporated in biomimetic interfaces, including biochemical factors, and well-designed chemical components that interact through weak interactions (e.g. H-bonds, hydrophobic and electrostatic interactions), exhibit chirality, or possess 'responsiveness'. The excellent, dynamic control of smart biointerfaces has a great influence on cell/substrate interactions and adsorption of biomacromolecules on the surface, and has become an important factor in the design of biomaterials. Precision chemistry has permitted the design of new molecules that, upon self-assembly, could form special nano-textures or hydrogels, which exhibit exclusive interaction with the biological milieu. Nano/micro-technologies have also been used to engineer interfaces with controlled topography across different length scales, permitting control over cellular and microbiological behaviour. By recreating highly-specific biological interactions, such technologies gave rise to biosensors that could be used in high-throughput and highly-sensitive biological assays. Control over the cell environment is frequently addressed in this special issue. An overview is presented on the combined effects of physical stimuli, such as mechanical properties and geometry, and growth factors when engineering advanced cellular microenvironments, providing impactful insight for fields involving stem cell technology, cancer research, and regenerative medicine (see article number 1700052). The 2D and 3D manipulation of the synthetic microenvironment, using both physical feature design and chemical modifications, can lead to platforms for a better understanding of neuronal growth mechanisms, and to ultimately advance the development of potential therapies for neuronal regeneration (see article number 1700267). In addition to applications in tissue repair, strategic cell manipulation can generate complex tissues to act as in vitro 3D-cancer models (see article number 1700057). Biomimetic microreactors are also able to support the function of living cells, for example by recreating the detoxification ability of hepatocytes (see article number 1601141). Hydrogels have been proposed to offer adequate 3D microenvironents to cells. Sophisticated cross-linking methodologies and design tools, such as the production of building blocks synthesized using click chemistry, can be employed to develop microgel-based systems to be used in tissue repair (see article number 1700254). Specially designed surfaces can provide specific functions to living cells. For example, surfaces can be specifically engineered to control bacterial adhesion and biofilm formation (see article number 1600948). The effect of surface nanotopography on cell behaviour was also focused on in this special issue: topographic features in titanium-based implants could influence preosteoblast morphology, adhesion and migration (see article number 1601244); nanogrooves imprinted on multilayered nanostructured films made from natural polymers could have an effective influence on cell proliferation, alignment, and differentiation (see article number 1601462); bioinspired surfaces exhibiting hierarchical topographic motifs of pollen could efficiently recognize cancer cells (see article number 1700003). Surfaces can also be modified with zwitterionic lipids as patternable, cell-repellent masks for selectively seeding cells (see article number 1700063). Such patterns could be used as a tool for the spatiotemporal control of cell distribution and cell-cell interactions. The understanding of the highly-specific mechanisms of biological interactions in combination with micro-technologies can be used to develop immunoassays using microfluidics is also reviewed in this special issue (see article number 1601403). Microfluidics can also be used in other applications, such as (1) to prepare rod-shaped neural tissue units with aligned nerve fibers that can be assembled to produce more complex 3D neural tissues (see article number 1700143), or (2) to establish a biomimetic tumor microenvironment model that reconstitutes the interactions of different tumor cells with cellular and non-cellular components that surround the tumor (see article number 1700196). The delivery of biological macromolecules or peptides is often hindered by the natural barriers. Mitragotri et al. suggest the use of non-conventional solvents for the transdermal delivery of therapeutic proteins (see article number 1601411). Proteins can also be used to kill selectively cancer cells: enzyme-instructed self-assembly is proposed as a new method to intracellularly generate nanofibrils of short peptides that selectively inhibit cancer cell proliferation (see article number 1601400). This set of publications is representative of the applicability and cutting-edge implementation of biomimetic interfaces in a wide-range of biomedical applications, and hopes to inspire novel, fundamental or applied research works in this field.