Asish C. Misra

Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering

The advancement of tissue engineering is contingent upon the development and implementation of advanced biomaterials. Conductive polymers have demonstrated potential for use as a medium for electrical stimulation, which has shown to be beneficial in many regenerative medicine strategies including neural and cardiac tissue engineering. Melanins are naturally occurring pigments that have previously been shown to exhibit unique electrical properties. This study evaluates the potential use of melanin films as a semiconducting material for tissue engineering applications. Melanin thin films were produced by solution processing and the physical properties were characterized. Films were molecularly smooth with a roughness (R(ms)) of 0.341 nm and a conductivity of 7.00+/-1.10 x 10(-5)S cm(-1) in the hydrated state. In vitro biocompatibility was evaluated by Schwann cell attachment and growth as well as neurite extension in PC12 cells. In vivo histology was evaluated by examining the biomaterial-tissue response of melanin implants placed in close proximity to peripheral nerve tissue. Melanin thin films enhanced Schwann cell growth and neurite extension compared to collagen films in vitro. Melanin films induced an inflammation response that was comparable to silicone implants in vivo. Furthermore, melanin implants were significantly resorbed after 8 weeks. These results suggest that solution-processed melanin thin films have the potential for use as a biodegradable semiconducting biomaterial for use in tissue engineering applications.

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 Orthogonal Three‐Patch Microparticles

Compared to two-dimensional substrates, only a few methodologies exist for the spatially controlled decoration of three-dimensional objects, such as microparticles. Combining electrohydrodynamic co-jetting with synthetic polymer chemistry, we were able to create two- and three-patch microparticles displaying chemically orthogonal anchor groups on three distinct surface patches of the same particle. This approach takes advantage of a combination of novel chemically orthogonal polylactide-based polymers and their processing by electrohydrodynamic co-jetting to yield unprecedented multifunctional microparticles. Several micropatterned particles were fabricated displaying orthogonal click functionalities. Specifically, we demonstrate novel two- and three-patch particles. Multi-patch particles are highly sought after for their potential to present multiple distinct ligands in a directional manner. This work clearly establishes a viable route towards orthogonal reaction strategies on multivalent micropatterned particles.

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.

Cardiomyocyte‐Driven Actuation in Biohybrid Microcylinders

Biohybrid microcylinders are fabricated using electrohydrodynamic cojetting followed by a surface chemistry approach to maximize cell-adhesive characteristics. As proper cell alignment and mechanical stiffness are important components of bioactuator design, spatial cell selectivity and stress/strain properties of microcylinders are characterized to demonstrate their capability of response to rat cardio-myocyte contraction. These microcylinders can find applications in a host of micromechanical systems.

Photoswitchable Particles for On-Demand Degradation and Triggered Release

On-demand degradable polymer particles are fabricated via electrospraying of a solution of acetal-protected dextran that further includes 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine as a photoacid generator. The illumination of UV light gives rise to photoacid and activates the catalytic deprotection of hydroxyl groups of dextran, leading to controlled dissolution of the microparticles in water.

Controlled microstructuring of Janus particles based on a multifunctional poly(ethylene glycol)

A novel water insoluble, multifunctional poly(ethylene glycol), poly(hydrazide ethylene glycol-co-benzyl glycidyl ether) (P(HZ-co-BnGE)), is synthesized via thiol-ene click reaction of poly(allyl glycidyl ether-co-benzyl glycidyl ether) (P(AGE-co-BnGE)). The base polymer P(AGE-co-BnGE) is previously prepared by anionic ring-opening copolymerization of the corresponding monomers. To demonstrate utility, bicompartmental microspheres and microcylinders containing P(HZ-co-BnGE) in one of the compartments are prepared via electrohydrodynamic (EHD) co-jetting. Next, spatially controlled surface reactivity toward sugars is demonstrated by selective binding of 2α-mannobiose to the P(HZ-co-BnGE) compartment only, as confirmed by a carbohydrate-lectin-binding assay. These sugar-reactive hydrazide-presenting microparticles have potential applications for glyco-targeted drug delivery.

Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

Abstract Background: Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Purpose: Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. Methods: EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Results and discussion: Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. Conclusion: EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site.

Progress of Multicompartmental Particles for Medical Applications

Particulate materials are becoming increasingly used in the literature for medical applications, but translation to the clinical setting has remained challenging as many particle systems face challenges from in vivo barriers. Multicompartmental particles that can incorporate several materials in an individual particle may allow for more intricate control and addressing of issues that otherwise standard particles are unable to. Here, some of the advances made in the use of multicompartmental particles for medical applications are briefly described.