Biomimetic Polymer Capsules: Novel Architecture and Properties

This study focuses on polymer capsules made from biocompatible, water-soluble polymers. Typically, the capsule core is a hydrogel in which proteins, nanoparticles, or biological cells can be encapsulated, while the capsule shell is permeable to small, but not large molecules. We explore two new designs or architectures for such capsules. One is a multi-compartment capsule (MCC) where a capsule has several distinct compartments inside it. A second design is a multilayer capsule, where concentric layers of different chemistries surround a core. These new designs mimic structures commonly found in nature such as a eukaryotic cell or an onion. Our goal is to exploit these novel capsule architectures to achieve new or improved properties. In our first study, we introduce a new kind of multilayer capsule, wherein a protective shell of covalently crosslinked polymer (acrylate) surrounds a core formed by physical crosslinking (alginate). Alginate capsules are widely used for cell-encapsulation, but they are quite weak. We show that a covalent acrylate shell can be added to these capsules in a single step under mild conditions. The shell protects the core from degradation while allowing the encapsulated cells to remain viable and functional. A variation of the synthesis technique yields capsules with two concentric shells (alginate, then acrylate) surrounding a liquid core. Next, we create MCCs in which microbes from two different kingdoms, i.e., bacteria (Pseudomonas aeruginosa) and fungi (Candida albicans), are placed next to each other in distinct inner compartments. This MCC platform holds advantages over traditional co-culture as it eliminates physical contact between the two microbes and allows for real-time monitoring of cell growth in 3D. Using this platform, we study the effects of both physical variables (e.g., pH) as well as chemical additives (e.g., surfactants) on the growth of the two populations. We also detect crosstalk between the bacteria and fungi, i.e., as the bacteria grow, they inhibit the formation of hyphal filaments by the fungi, which make the fungi less invasive. Lastly, we create MCCs with ‘smart’ inner compartments, which are sensitive to various stimuli. An analogy is drawn to different organelles in a cell, which have different constituents and unique functions. We select the chemistry or architecture of each inner compartment of the MCC such that their responses are distinct and orthogonal. For example, one compartment alone breaks apart when the MCC is contacted with an enzyme, while another gets degraded by the introduction of hydrogen peroxide (H2O2), and a third is disrupted by ultraviolet (UV) light. Another concept is shown where the degradation of one compartment induces the degradation of another. We believe these new designs will make the MCC platform more attractive for various biological applications