Spatiotemporal Control over Molecular Delivery and Cellular Encapsulation from Electropolymerized Micro‐ and Nanopatterned Surfaces

Abstract

Bioactive, patterned micro-and nanoscale surfaces that can be spatially engineered for threedimensional ligand presentation and sustained release of signaling molecules represent a critical advance for the development of next-generation diagnostic and therapeutic devices. Lithography is ideally suited to patterning such surfaces due to its precise, easily scalable, high-throughput nature; however, to date polymers patterned by these techniques have not demonstrated the capacity for sustained release of bioactive agents. We demonstrate here a class of lithographically-defined, electropolymerized polymers with monodisperse micro-and nanopatterned features capable of sustained release of bioactive drugs and proteins. We show that precise control can be achieved over the loading capacity and release rates of encapsulated agents and illustrate this aspect using a fabricated surface releasing a model antigen (ovalbumin) and a cytokine (interleukin-2) for induction of a specific immune response. We further demonstrate the ability of this technique to enable threedimensional control over cellular encapsulation. The efficacy of the described approach is buttressed by its simplicity, versatility, and reproducibility, rendering it ideally suited for biomaterials engineering.

Shrink Wrapping Cells in a Defined Extracellular Matrix to Modulate the Chemo-Mechanical Microenvironment

“…In another approach, micropatterned surfaces were used to encapsulate cells in a pyrole-alginate hydrogel that simultaneously could perform controlled release of protein. 30 This system enabled the controlled presentation of soluble and in soluble factors while maintaining high cell viability. Recent work has also demonstrated that encapsulation materials based on polydimethylsiloxane (PDMS) and calcium peroxide can actively release oxygen to support metabolic activity in larger constructs that would otherwise suffer from hypoxia-induced necrotic cores.…”

The Use of a Hydrogel Matrix as a Cellular Delivery Vehicle in Future Cell-Based Therapies: Biological and Non-Biological Considerations

“…raw materials and cGMP costs are low) and the marketplace's acceptance of a fair price. As a final thought, while there is a great deal of academic excitement and publication activity surrounding the development of ever-increasingly complex cellular delivery matrices that can replicate a new aspect of a stem cell niche (Engler, et al, 2006;Phillips, et al, 2008;Reilly and Engler, 2009;Stern, et al, 2009;Wosnick and Shoichet, 2008), the question is: after a point, when is more complexity in a cellular delivery vehicle too much?…”

Electrochemical Actuators: Controlled Drug Release Strategies for use in Micro Devices

“…A large number of strategies have been investigated and include: conducting polymers 36–46, carbon nano‐structure composites 47–50, hydrogels 51–54, nano and mesoporous electrodes 55–58, pump systems 59–67 and reductive cleavage of immobilised drugs 68. The chemistry and electrochemical transitions which facilitate their adaptation to drug delivery strategies are considered in turn in the following subsections.…”

“…The use of conducting polymers such as polypyrrole, polythiophene and polyphenylene‐vinylene have a rich history in sensing applications but they have also been shown to serve as drug eluting actuators 36–47. The redox transitions of the polymer leads not only to the capture and expulsion of anions, but also a physical swelling and shrinkage – all of which can be manipulated to involve suitable drug candidates.…”