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      Programming Stimuli-Responsive Behavior into Biomaterials

      1 , 1 , 2 , 3 , 4

      Annual Review of Biomedical Engineering

      Annual Reviews

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          Abstract

          Stimuli-responsive materials undergo triggered changes when presented with specific environmental cues. These dynamic systems can leverage biological signals found locally within the body as well as exogenous cues administered with spatiotemporal control, providing powerful opportunities in next-generation diagnostics and personalized medicine. Here, we review the synthetic and strategic advances used to impart diverse responsiveness to a wide variety of biomaterials. Categorizing systems on the basis of material type, number of inputs, and response mechanism, we examine past and ongoing efforts toward endowing biomaterials with customizable sensitivity. We draw an analogy to computer science, whereby a stimuli-responsive biomaterial transduces a set of inputs into a functional output as governed by a user-specified logical operator. We discuss Boolean and non-Boolean operations, as well as the various chemical and physical modes of signal transduction. Finally, we examine current limitations and promising directions in the ongoing development of programmable stimuli-responsive biomaterials.

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          Most cited references 103

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          A logic-gated nanorobot for targeted transport of molecular payloads.

          We describe an autonomous DNA nanorobot capable of transporting molecular payloads to cells, sensing cell surface inputs for conditional, triggered activation, and reconfiguring its structure for payload delivery. The device can be loaded with a variety of materials in a highly organized fashion and is controlled by an aptamer-encoded logic gate, enabling it to respond to a wide array of cues. We implemented several different logical AND gates and demonstrate their efficacy in selective regulation of nanorobot function. As a proof of principle, nanorobots loaded with combinations of antibody fragments were used in two different types of cell-signaling stimulation in tissue culture. Our prototype could inspire new designs with different selectivities and biologically active payloads for cell-targeting tasks.
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            Designing hydrogels for controlled drug delivery

            Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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              Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change.

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                Author and article information

                Journal
                Annual Review of Biomedical Engineering
                Annu. Rev. Biomed. Eng.
                Annual Reviews
                1523-9829
                1545-4274
                June 04 2019
                June 04 2019
                : 21
                : 1
                : 241-265
                Affiliations
                [1 ]Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, USA;
                [2 ]Department of Bioengineering, University of Washington, Seattle, Washington 98105, USA
                [3 ]Institute of Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA
                [4 ]Molecular Engineering and Sciences Institute, University of Washington, Seattle, Washington 98195, USA
                Article
                10.1146/annurev-bioeng-060418-052324
                © 2019

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