Microencapsulation of Live Cells in Synthetic Polymer Capsules

In cell therapies, it is advantageous to encapsulate live cells in protective, semipermeable microparticles for controlled release of cytokines, growth factors, monoclonal antibodies, or insulin. Here, a modified electrospraying approach with an organic solution of poly­(lactide-<i>co</i>-glycolide) (PLGA) polymer is used to create synthetic PLGA capsules that effectively protect live cells. Using a design of experiment (DOE) methodology, the effect of governing jetting parameters on encapsulation efficiency, yield, and size is systematically evaluated. On the basis of this analysis, the interaction between bovine serum albumin concentration and core flow rate is the most dominant factor determining core encapsulation efficiency as well as the microcapsule size. However, the interaction between shell solvent ratio and shell flow rate predominantly defines the particle yield. To validate these findings, live cells have been successfully encapsulated in microcapsules using optimized parameters from the DOE analysis and have survived the electrohydrodynamic jetting process. Extending the currently available toolkit for cell microencapsulation, these biodegradable, semi-impermeable cell-laden microcapsules may find a range of applications in areas such as tissue engineering, regenerative medicine, and drug delivery

Systematic Studies into the Area Selectivity of Chemical Vapor Deposition Polymerization

As the current top-down microchip manufacturing processes approach their resolution limits, there is a need for alternative patterning technologies that offer high feature densities and edge fidelity with single-digit nanometer resolution. To address this challenge, bottom-up processes have been considered, but they typically require sophisticated masking and alignment schemes and/or face materials’ compatibility issues. In this work, we report a systematic study into the impact of thermodynamic processes on the area selectivity of chemical vapor deposition (CVD) polymerization of functional [2.2]paracyclophanes (PCP). Adhesion mapping of preclosure CVD films by atomic force microscopy (AFM) provided a detailed understanding of the geometric features of the polymer islands that form under different deposition conditions. Our results suggest a correlation between interfacial transport processes, including adsorption, diffusion, and desorption, and thermodynamic control parameters, such as substrate temperature and working pressure. This work culminates in a kinetic model that predictes both area-selective and nonselective CVD parameters for the same polymer/substrate ensemble (PPX-C + Cu). While limited to a focused subset of CVD polymers and substrates, this work provides an improved mechanistic understanding of area-selective CVD polymerization and highlights the potential for thermodynamic control in tuning area selectivity

Examining Nanoparticle Adsorption on Electrostatically “Patchy” Glycopolymer Brushes Using Real-Time ζ‑Potential Measurements

Biomaterial surfaces can possess chemical, topographical, or electrostatic heterogeneity, which can profoundly influence their performance. By developing experimental models that reliably simulate this nanoscale heterogeneity, we can predict how heterogeneous surfaces are transformed by their interactions with the dynamic physiological environment. In this work, we present a model surface where well-defined glycopolymer brushes are interspersed with positively charged binding sites, giving rise to an interface presenting a mixture of repulsive and adhesive cues to an approaching virus particle. We show that the density of the affinity sites relative to the glycopolymer brushes can be tuned precisely by modifying the chemical vapor deposition (CVD) copolymerization conditions. Further, we examined the effects of binding site density and glycopolymer brush architecture on the adsorption kinetics of virus-like nanoparticles through a novel approach employing time-resolved ζ-potential measurements. Most materials have charge-bearing, dynamic surfaces that are sensitive to electrostatic effects. Hence, adsorption-triggered changes in ζ-potential measurements can be captured in real time to monitor interfacial events. Real-time ζ-potential measurements present an interesting platform to probe the structure and function of chemically and electrostatically heterogeneous polymer interfaces. To validate this electrokinetic method, we examined the effect of neutravidin concentration on its rate of binding to biotinylated surfaces using ζ-potential and compared our results with QCM studies. By applying electrokinetic methods to examine the roles of glycopolymer brush architecture and surface charge of these tunable glycopolymer coatings, we can enhance our understanding of the interactions of viruses with heterogeneous biomaterial interfaces

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

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

Dual-Stimuli-Responsive Microparticles

The need for smart materials in the area of biotechnology has fueled the development of numerous stimuli-responsive polymers. Many of these polymers are responsive to pH, light, temperature, or oxidative stress, and yet very few are responsive toward multiple stimuli. Here we report on the synthesis of a novel dual-stimuli-responsive poly­(ethylene glycol)-based polymer capable of changing its hydrophilic properties upon treatment with UV light (exogenous stimulus) and markers of oxidative stress (endogenous stimulus). From this polymer, smart microparticles and fibers were fabricated and their responses to either stimulus separately and in conjunction were examined. Comparison of the degradation kinetics demonstrated that the polymer became water-soluble only after both oxidation and irradiation with UV light, which resulted in selective degradation of the corresponding particles. Furthermore, in vitro experiments demonstrated successful uptake of these particles by Raw 264.7 cells. Such dual-stimuli-responsive particles could have potential applications in drug delivery, imaging, and tissue engineering

Janus-Core and Shell Microfibers

Janus microcylinders composed of different polymers were prepared through coaxial co-jetting with dual-core flows, followed by cross-linking, microsectioning, and shell removal. Uniquely shaped building blocks can be fabricated by photo-patterning of one hemisphere of the microcylinders

CXCR4-Targeted Nanocarriers for Triple Negative Breast Cancers

CXCR4 is a cell membrane receptor that is overexpressed in triple-negative breast cancers and implicated in growth and metastasis of this disease. Using electrohydrodynamic cojetting, we prepared multicompartmental drug delivery carriers for CXCR4 targeting. The particles are comprised of a novel poly­(lactide-<i>co</i>-glycolide) derivative that allows for straightforward immobilization of 1,1′-[1,4-phenylenebis­(methylene)]­bis­[1,4,8,11-tetraazacyclotetradecane] (Plerixafor), a small molecule with affinity for CXCR4. Targeted nanocarriers are selectively taken up by CXCR4-expressing cells and effectively block CXCR4 signaling. This study suggests that CXCR4 may be an effective target for nanocarrier-based therapies

Selective and Reversible Binding of Thiol-Functionalized Biomolecules on Polymers Prepared via Chemical Vapor Deposition Polymerization

We use chemical vapor deposition polymerization to prepare a novel dibromomaleimide-functionalized polymer for selective and reversible binding of thiol-containing biomolecules on a broad range of substrates. We report the synthesis and CVD polymerization of 4-(3,4-dibromomaleimide)­[2.2]­paracyclophane to yield nanometer thick polymer coatings. Fourier transformed infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the chemical composition of the polymer coating. The reactivity of the polymer coating toward thiol-functionalized molecules was confirmed using fluorescent ligands. As a proof of concept, the binding and subsequent release of cysteine-modified peptides from the polymer coating were also demonstrated via sum frequency generation spectroscopy. This reactive polymer coating provides a flexible surface modification approach to selectively and reversibly bind biomolecules on a broad range of materials, which could open up new opportunities in many biomedical sensing and diagnostic applications where specific binding and release of target analytes are desired

Bioinstructive Coatings for Hematopoietic Stem Cell Expansion Based on Chemical Vapor Deposition Copolymerization

We report the chemical vapor deposition (CVD) of dual-functional polymer films for the specific and orthogonal immobilization of two biomolecules (notch ligand delta-like 1 (DLL1) and an RGD-peptide) that govern the fate of hematopoietic stem and progenitor cells. The composition of the CVD polymer and thus the biomolecule ratio can be tailored to investigate and optimize the influence of the relative surface concentrations of biomolecules on stem cell behavior. Prior to cell experiments, all surfaces were characterized by infrared reflection adsorption spectroscopy, time-of-flight secondary ion mass spectrometry, and X-ray photoelectron spectroscopy to confirm the presence of both biomolecules. In a proof-of-principle stem cell culture study, we show that all polymer surfaces are cytocompatible and that the proliferation of the hematopoietic stem and progenitor cells is predominantly influenced by the surface concentration of immobilized DLL1