Srijanani Bhaskar

Red blood cell-mimicking synthetic biomaterial particles

Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.

Towards Designer Microparticles: Simultaneous Control of Anisotropy, Shape, and Size

Biodegradable, compositionally anisotropic microparticles with two distinct compartments that exhibit controlled shapes and sizes are fabricated. These multifunctional particles are prepared by electrohydrodynamic co-jetting of poly(lactide-co-glycolide) polymer solutions. By varying different solution and process parameters, namely, concentration and flow rate, a variety of non-equilibrium bicompartmental shapes, such as discoid and rod-shaped microparticles are produced in high yields. Optimization of jetting parameters, combined with filtration, results in near-perfect, bicompartmental spherical particles in the size range of 3-5 microm. Simultaneous control over anisotropy, size, shape, and surface structure provides an opportunity to create truly multifunctional microparticles for a variety of biological applications, such as drug delivery, diagnostic assays, and theranostics.

Structurally Controlled Bio‐hybrid Materials Based on Unidirectional Association of Anisotropic Microparticles with Human Endothelial Cells

Biocompatible anisotropic polymer particles with bipolar affinity towards human endothelial cells are a novel type of building blocks for microstructured bio-hybrid materials. Functional polarity due to two biologically distinct hemispheres has been achieved by synthesis of anisotropic particles via electro-hydrodynamic co-jetting of two different polymer solutions and subsequent selective surface modification.

Spontaneous shape reconfigurations in multicompartmental microcylinders

Nature’s particles, such as spores, viruses or cells, are adaptive—i.e., they can rapidly alter major phenomenological attributes such as shape, size, or curvature in response to environmental changes. Prominent examples include the hydration-mediated opening of ice plant seeds, actuation of pine cones, or the ingenious snapping mechanism of predatory Venus flytraps that rely on concave-to-convex reconfigurations. In contrast, experimental realization of reconfigurable synthetic microparticles has been extremely challenging and only very few examples have been reported so far. Here, we demonstrate a generic approach towards dynamically reconfigurable microparticles that explores unique anisotropic particle architectures, rather than direct synthesis of sophisticated materials such as shape-memory polymers. Solely enabled by their architecture, multicompartmental microcylinders made of conventional polymers underwent active reconfiguration including shape-shifting, reversible switching, or three-way toggling. Once microcylinders with appropriate multicompartmental architectures were prepared by electrohydrodynamic cojetting, simple exposure to an external stimulus, such as ultrasound or an appropriate solvent, gives rise to interfacial stresses that ultimately cause reversible topographical reconfiguration. The broad versatility of the electrohydrodynamic cojetting process with respect to materials selection and processing suggests strategies for a wide range of dynamically reconfigurable adaptive materials including those with prospective applications for sensors, reprogrammable microactuators, or targeted drug delivery.

Microstructured Materials Based on Multicompartmental Fibers

We demonstrate herein the fabrication of novel multicompartmental biodegradable microstructures via electrohydrodynamic cospinning of two or more polymer solutions. Under optimized processing conditions, the interface between the solutions can be sustained continuously for long time intervals, yielding fibers with multiple chemically distinct compartments. Simultaneous control over internal fiber architecture and the spatial arrangement of individual compartments combined with precise long-range fiber alignment makes these fibers potential candidates for applications such as tissue engineering or cell culture studies.

Multicompartmental Particles for Combined Imaging and siRNA Delivery

The controlled delivery of genetic material, such as genes, plasmids, or siRNA, holds great promise for the therapy of a number of debilitating diseases. [ 1–3 ] While the fundamental concept of permanent or temporary genetic manipulation has been widely embraced by the scientifi c community, severe concerns remain about the safe and effi cient transfer of the genetic material into human cells, where it needs to be released in order to interact with the cell nucleus. [ 1 , 2 , 4 ] In addition it is desirable, in many cases, to combine gene delivery with a secondary function, such as release of a chemotherapeutic agent or an imaging modality. The main delivery challenges fall broadly into two categories: fi rst, the cell membrane represents an effective barrier against the infl ux of foreign genetic material resulting in notoriously low transfection rates. Second, a host of nucleases exist in the human body, which cause rapid breakdown of any unprotected genetic material. A number of approaches have been developed to address these challenges including electroporation, [ 5 ] viral vectors, [ 6 , 7 ] cationic liposomal formulations, [ 1 ] and nanoparticles. [ 1 , 2 ]

Chemically Controlled Bending of Compositionally Anisotropic Microcylinders

Soft materials that can undergo mechanical actuation in response to external stimuli, such as changes in temperature, light, pH value, or ionic strength, have attracted increasing attention because of their potential use as thinfilm actuators, smart sutures, and soft robots. These materials typically require specialty polymers, such as shape-memory polymers or use macroscopically layered films. In layered films, the anisotropic distribution of two polymers, or a polymer and a metal, is essential. This creates a mismatch in mechanical properties that gives rise to a defined bending. In principle, this concept is not limited to macroscopic multilayer films, but can be achieved with colloidal materials, as long as the required anisotropy can be realized and different parts of the colloidal object will respond differently to the external stimulus. In recent years, compositionally anisotropic microand nanoparticles have been devised using a range of different synthesis methods including microfluidic and lithographic techniques, particle replication in low surface energy templates, selective crosslinking of polybutadiene segments in terpolymers, lithographic patterning of microspheres, electrochemical and photochemical reduction, templating of porous membranes and nanotubes, surfactant aided growth, graft polymerization, and processes based on controlled surface nucleation. Alternatively, electrohydrodynamic co-jetting is a method to prepare particles and fibers with multiple compartments by transferring fluids through a set of capillaries that can process dissimilar materials. In the past, electrohydrodynamic co-jetting has resulted in particles with multiple compartments that contain different polymer blends, dyes, low-molecular weight additives, reactive molecules and even inorganic nanoparticles. If a reactive additive, such as a functionalized polymer, is added to one of the compartments, selective surface modification is possible and can result in spatially controlled immobilization of proteins or peptides. Because different compartments can be loaded with dissimilar materials, entirely new sets of functions can arise from unique synergistic effects, not just from the addition of the properties of the individual compartments. Herein, we report a new type of compositionally anisotropic microcylinders, where defined compartments within the same microcylinder undergo differential expansion due to the site-selective growth of a surface layer. The asymmetric expansion creates surface stresses resulting in significant and controllable bending of the microcylinders, which depends on the particle geometry and the architecture of the surface layers. Using finite element simulations, we verify the observed bending trends and derive a family of performance curves that predict a wide-range tunability of the actuation stroke based on the cylinder geometry and the amount of swelling. The microcylinders are fabricated based on electrohydrodynamic co-jetting followed by microsectioning. In brief, an electric field is applied to a compound droplet comprising two or more polymer solutions generated by laminar flow from a side-by-side arrangement of capillary needles. We have previously demonstrated the synthesis of particles and fibers from chloroform-based solutions of lactic acid polymers. In the case of fibers, high viscosities, combined with high solvent volatility and low charge-to-volume ratios, can result in an extremely linear and controlled jet migration without the bending and whipping instabilities commonly observed in charged jets. This situation enables the production of multicompartmental microfibers, which not only exhibit monodispersity with respect to diameter, but can also be aligned on rotating collectors. Such highly aligned fiber scaffolds can then be cut into monodisperse microcylinders. Importantly, particle diameters are controlled by altering the solution and process parameters during electrohydrodynamic co-jetting, while control over cylinder length is achieved by the microsectioning step. Spatioselective functionalization of one or more compartments of the cylinders has been achieved by incorporation of poly(lactide-co-propargyl glycolide) as an additive during fabrication of the microcylinders, and subsequent modification with biotin and streptavidin by click chemistry. As shown in the Supporting Information, Figure S1, we incorporated a poly[lactide-co[*] Dr. S. Saha, N. Clay, A. Donini, Prof. J. Lahann Department of Chemical Engineering University of Michigan, Ann Arbor, MI 48109 (USA) E-mail: lahann@umich.edu

Amphiphilic Colloidal Surfactants Based on Electrohydrodynamic Co-jetting

A novel synthetic route for the preparation of amphiphilic Janus particles based on electrohydrodynamic cojetting has been developed. In this approach, selective encapsulation of hydrophobic fluorodecyl-polyhedral oligomeric silsesquioxane (F-POSS) in one compartment and a poly(vinyl alcohol) in the second compartment results in colloidal particles with surfactant-like properties including the self-organization at oil-water and air-water interfaces. Successful localization of the respective polymers in different compartments of the same particle is confirmed by a combination of fluorescence microscopy, vibrational spectroscopy, and ζ-potential measurements. We believe that this straightforward synthetic approach may lead to a diverse class of surface-active colloids that will have significant relevance ranging from basic scientific studies to immediate applications in areas, such as pharmaceutical sciences or cosmetics.

Micropatterned Fiber Scaffolds for Spatially Controlled Cell Adhesion

Because the local microstructure plays a pivotal role for many biological functions, a wide range of methods have been developed to design precisely engineered substrates for both fundamental biological studies and biotechnological applications. However, these techniques have been by-and-large limited to flat surfaces. Herein, we use electrohydrodynamic co-spinning to prepare biodegradable three-dimensional fiber scaffolds with precisely engineered, micrometre-scale patterns, wherein each fiber is comprised of two distinguishable compartments. When bicompartmental fiber scaffolds are modified via spatially controlled peptide immobilization, highly selective cell guidance at spatial resolutions (<10 µm), so far exclusively reserved for flat substrates, is achieved. Microstructured fiber scaffolds may have utility for a range of biotechnological applications including tissue engineering or cell-based assays.

Compartmentalized Photoreactions within Compositionally Anisotropic Janus Microstructures

We demonstrate spatially controlled photoreactions within bicompartmental microparticles and microfibers. Selective photoreactions are achieved by anisotropic incorporation of photocrosslinkable poly(vinyl cinnamate) in one compartment of either colloids or microfibers. Prior to photoreaction, bicompartmental particles, and fibers were prepared by EHD co-jetting of two compositionally distinct polymer solutions. Physical and chemical anisotropy was confirmed by confocal laser scanning microscopy, Fourier-transformed infrared spectroscopy, and scanning electron microscopy. The data indicate adjustment of polymer concentrations of the jetting solutions to be the determining factors for particle and fiber structures. Subsequent exposure of poly(vinyl cinnamate)-based particles and fibers to UV light at 254 nm resulted in spatially controlled crosslinking. Treatment of the crosslinked bicompartmental colloids with chloroform produced half-moon shaped objects. These hemishells exhibited a distinct porous morphology with pore sizes in the range of 70 nm. Based on this novel synthetic approach, Janus-type particles and fibers can be prepared by EHD co-jetting and can be selectively photocrosslinked without the need for masks or selective laser writing.