Resorbable barrier polymers for flexible bioelectronics.

Resorbable, implantable bioelectronic devices are emerging as powerful tools to reliably monitor critical physiological parameters in real time over extended periods. While degradable magnesium-based electronics have pioneered this effort, relatively short functional lifetimes have slowed clinical translation. Barrier films that are both flexible and resorbable over predictable timelines would enable tunability in device lifetime and expand the viability of these devices. Herein, we present a library of stereocontrolled succinate-based copolyesters which leverage copolymer composition and processing method to afford tunability over thermomechanical, crystalline, and barrier properties. One copolymer composition within this library has extended the functional lifetime of transient bioelectronic prototypes over existing systems by several weeks-representing a considerable step towards translational devices.

Influence of Touch-Spun Nanofiber Diameter on Contact Guidance during Peripheral Nerve Repair.

Peripheral nerve regeneration across large gaps remains clinically challenging and scaffold design plays a key role in nerve tissue engineering. One strategy to encourage regeneration has utilized nanofibers or conduits to exploit contact guidance within the neural regenerative milieu. Herein, we report the effect of nanofiber topography on two key aspects of regeneration: Schwann cell migration and neurite extension. Substrates possessing distinct diameter distributions (300 ± 40 to 900 ± 70 nm) of highly aligned poly(ε-caprolactone) nanofibers were fabricated by touch-spinning. Cell migratory behavior and contact guidance were then evaluated both at the tissue level using dorsal root ganglion tissue explants and the cellular level using dissociated Schwann cells. Explant studies showed that Schwann cells emigrated significantly farther on fibers than control. However, both Schwann cells and neurites emigrated from the tissue explants directionally along the fibers regardless of their diameter, and the data were characterized by high variation. At the cellular level, dissociated Schwann cells demonstrated biased migration in the direction of fiber alignment and exhibited a significantly higher biased velocity (0.2790 ± 0.0959 µm·min-1) on 900 ± 70 nm fibers compared to other nanofiber groups and similar to the velocity found during explant emigration on 900 nm fibers. Therefore, aligned, nanofibrous scaffolds of larger diameters (900 ± 70 nm) may be promising materials to enhance various aspects of nerve regeneration via contact guidance alone. While cells track along with the fibers, this contact guidance is bidirectional along the fiber, moving in the plane of alignment. Therefore, the next critical step to direct regeneration is to uncover haptotactic cues that enhance directed migration.

Arene-perfluoroarene interactions confer enhanced mechanical properties to synthetic nanotubes.

Supramolecular nanotubes prepared through macrocycle assembly offer unique properties that stem from their long-range order, structural predictability, and tunable microenvironments. However, assemblies that rely on weak non-covalent interactions often have limited aspect ratios and poor mechanical integrity, which diminish their utility. Here pentagonal imine-linked macrocycles are prepared by condensing a pyridine-containing diamine and either terephthalaldehyde or 2,3,5,6-tetrafluoroterephthalaldehyde. Atomic force microscopy and synchrotron in solvo X-ray diffraction demonstrate that protonation of the pyridine groups drives assembly into high-aspect ratio nanotube assemblies. A 1 : 1 mixture of each macrocycle yielded nanotubes with enhanced crystallinity upon protonation. UV-Vis and fluorescence spectroscopy indicate that nanotubes containing both arene and perfluoroarene subunits display spectroscopic signatures of arene-perfluoroarene interactions. Touch-spun polymeric fibers containing assembled nanotubes prepared from the perhydro- or perfluorinated macrocycles exhibited Young's moduli of 1.09 and 0.49 GPa, respectively. Fibers containing nanotube assemblies reinforced by arene-perfluoroarene interactions yielded a 93% increase in the Young's modulus over the perhydro derivative, up to 2.1 GPa. These findings demonstrate that tuning the chemical composition of the monomeric macrocycles can have profound effects on the mechanical strength of the resulting assemblies. More broadly, these results will inspire future studies into tuning orthogonal non-covalent interactions between macrocycles to yield nanotubes with emergent functions and technological potential.

Shape Memory Behavior of Biocompatible Polyurethane Stereoelastomers Synthesized via Thiol-Yne Michael Addition.

Biodegradable shape memory elastomers have the potential for use in soft tissue engineering, drug delivery, and device fabrication applications. Unfortunately, few materials are able to meet the targeted degradation and mechanical properties needed for long-term implantable devices. In order to overcome these limitations, we have designed and synthesized a series of unsaturated polyurethanes that are elastic, degradable, and nontoxic to cells in vitro. The polymerization included a nucleophilic thiol-yne Michael addition between a urethane-based dipropiolate and a dithiol to yield an α,ß-unsaturated carbonyl moiety along the polymer backbone. The alkene stereochemistry of the materials was tuned between 32 and 82% cis content using a combination of an organic base and solvent polarity, which collectively direct the nucleophilic addition. The bulk properties such as tensile strength, modulus, and glass transition temperature can also be tuned broadly, and the hydrogen bonding imparted by the urethane moiety allows for these materials to elicit cyclic shape memory behavior. We also demonstrated that the in vitro degradation properties are highly dependent on the alkene stereochemistry.

Fabrication of Biomedical Scaffolds Using Biodegradable Polymers.

Degradable polymers are used widely in tissue engineering and regenerative medicine. Maturing capabilities in additive manufacturing coupled with advances in orthogonal chemical functionalization methodologies have enabled a rapid evolution of defect-specific form factors and strategies for designing and creating bioactive scaffolds. However, these defect-specific scaffolds, especially when utilizing degradable polymers as the base material, present processing challenges that are distinct and unique from other classes of materials. The goal of this review is to provide a guide for the fabrication of biodegradable polymer-based scaffolds that includes the complete pathway starting from selecting materials, choosing the correct fabrication method, and considering the requirements for tissue specific applications of the scaffold.

Gravity Drawing of Micro- and Nanofibers for Additive Manufacturing of Well-Organized 3D-Nanostructured Scaffolds.

This work introduces a gravity fiber drawing (GFD) method of making single filament nanofibers from polymer solutions and precise alignment of the fibers in 3D scaffolds. This method is advantageous for nanofiber 3D alignment in contrast to other known methods. GFD provides a technology for the fabrication of freestanding filament nanofibers of well-controlled diameter, draw ratio, and 3D organization with controllable spacing and angular orientation between nanofibers. The GFD method is capable of fabricating complex 3D scaffolds combining fibers with different diameters, chemical compositions, mechanical properties, angular orientations, and multilayer structures in the same construct. The scaffold porosity can be as high as 99% to secure transport of nutrients and space for cell infiltration and differentiation in tissue engineering and 3D cell culture applications.

Enhanced neuronal differentiation of neural stem cells with mechanically enhanced touch-spun nanofibrous scaffolds.

We studied NE-4C neural cells differentiation on 2D polycaprolactone (PCL) nanofibrous scaffolds with systematically varied mechanical characteristics of nanofibers while retaining an unchanged fiber alignment, diameter, and chemical composition. Our experiments demonstrated that the nanofibers with enhanced mechanical properties are beneficial for the preferential development of neuronal cells vs. glial cells. Electrospun (ES) and touch-spun (TS) nanofibers were fabricated with Young's modulus in the range of 10 MPa to 230 MPa and a fraction of crystallinity from 30% to 80%. The TS fibers undergo a greater drawing ratio and thus approach a greater polymer chain stretching and alignment that resulted in an increased crystallinity. The TS scaffolds demonstrated improved stability in the aqueous cell culture environment, resisting misalignment and entanglement after a period of 2 weeks of swelling followed by 14 days of neural differentiation. The results confirmed that the neurites on the TS fibers have a preferred orientation even after swelling.

Adaptive Hybrid Molecular Brushes Composed of Chitosan, Polylactide, and Poly(N-vinyl pyrrolidone) for Support and Guiding Human Dermal Fibroblasts.

Hybrid molecular brushes (HMBs) are macromolecular constructs made up of a backbone polymer and side-chain polymers with distinct properties. They adapt to a changing microenvironment via the conformational mechanism and thus may affect mammalian cell proliferation. Two biobenign HMBs were synthesized in this work: (1) polylactide (PLA) grafted to the chitosan (CHI) backbone to form chitosan-graft-polylactide (CHI-g-PLA), a two-component molecular brush, and (2) poly(N-vinyl pyrrolidone) (PNVP) grafted to chitosan moieties of CHI-g-PLA to form a three-component HMB. The molecular brushes were used to fabricate polymer coatings and nanofibers, guiding the attachment and growth of human dermal fibroblasts (HDFs) while silencing the response of macrophages to the scaffolds. The exterior surface composition of the coatings can be switched by exposure to solvents of different polarities: hydrophilic PNVP chains upon exposure to water or hydrophobic PLA chains upon treatment by anisole. Our experiments demonstrate substantial improvement of the HDF cell attachment and proliferation on the surface of the HMBs as compared to the parent polymers CHI, PLA, and PNVP. A Sirius Red assay and immunofluorescence show that HMBs stimulate production of collagen by HDF cells, which propagate on the polymer substrates revealing well-developed focal adhesion structures. On the other hand, a low attachment of macrophages is observed on the HMB surfaces, in particular if HMBs are switched to the hydrophilic state, i.e., PNVP in the top strata.

Touch-Spun Nanofibers for Nerve Regeneration.

In the current study, we examined the potential for neural stem cell (NSCs) proliferation on novel aligned touch-spun polycaprolactone (PCL) nanofibers. Electrospun PCL nanofibers with similar diameter and alignment were used as a control. Confocal microscopy images showed that NSCs grew and differentiated all over the scaffolds up to 8 days. Neurite quantification analysis revealed that the NSCs cultured on the touch-spun fibers with incorporated bovine serum albumin promoted the expression of neuron-specific class III ß-tubulin after 8 days. More importantly, NSCs grown on the aligned touch-spun PCL fibers exhibited a bipolar elongation along the direction of the fiber, while NSCs cultured on the aligned electrospun PCL fibers expressed a multipolar elongation. The structural characteristics of the PCL nanofibers analyzed by X-ray diffraction indicated that the degree of crystallinity and elastic modulus of the touch-spun fiber are significantly higher than those of electrospun fibers. These findings indicate that the aligned and stiff touch-spun nanofibrous scaffolds show considerable potential for nerve injury repair.

Cooperative Self-Assembly of Pyridine-2,6-Diimine-Linked Macrocycles into Mechanically Robust Nanotubes.

Nanotubes assembled from macrocyclic precursors offer a unique combination of low dimensionality, structural rigidity, and distinct interior and exterior microenvironments. Usually the weak stacking energies of macrocycles limit the length and mechanical strength of the resultant nanotubes. Imine-linked macrocycles were recently found to assemble into high-aspect ratio (>103 ), lyotropic nanotubes in the presence of excess acid. Yet these harsh conditions are incompatible with many functional groups and processing methods, and lower acid loadings instead catalyze macrocycle degradation. Here we report pyridine-2,6-diimine-linked macrocycles that assemble into high-aspect ratio nanotubes in the presence of less than 1 equiv of CF3 CO2 H per macrocycle. Analysis by gel permeation chromatography and fluorescence spectroscopy revealed a cooperative self-assembly mechanism. The low acid concentrations needed to induce assembly enabled nanofibers to be obtained by touch-spinning, which exhibit higher Young's moduli (1.33 GPa) than many synthetic polymers and biological filaments. These findings represent a breakthrough in the design of inverse chromonic liquid crystals, as assembly under such mild conditions will enable the design of structurally diverse and mechanically robust nanotubes from synthetically accessible macrocycles.

Touch- and Brush-Spinning of Nanofibers.

Robust, simple, and scalable touch- and brush-spinning methods for the drawing of nanofibers, core-shell nanofibers, and their aligned 2D and 3D meshes using polymer solutions and melts are discussed.

Reactive Magnetospinning of Nano- and Microfibers.

Reactive spinning of nano- and microfibers that involves very fast chemical reactions and ion exchange is a challenge for the common methods for nanofiber formation. Herein, we introduce the reactive magnetospinning method. This procedure is based on the magnetic-field-directed collision of ferrofluid droplets with liquid droplets that contain complementary reactants. The collision, start of the chemical reaction, and the fiber drawing are self-synchronized. The method is used to synthesize, cross-link, and chemically modify fiber-forming polymers in the stage of fiber formation. The method provides new opportunities for the fabrication of nanofibers for biomedical applications.

Conversion of metallic single-walled carbon nanotube networks to semiconducting through electrochemical ornamentation.

Field-effect transistors (FETs) that incorporate single-walled carbon nanotube (SWNT) networks experience decreased on-off current ratios (I(on)/I(off)) due to the presence of metallic nanotubes. Herein, we describe a method to increase I(on)/I(off) without the need for either specialized SWNT growth methods or post growth processing steps to remove metallic nanotubes. SWNTs that were grown using conventional arc discharge methods were deposited from aqueous suspension. Then, the SWNTs in the network were decorated with Cu2O nanoparticles that acted as controllable valves that restricted current flow at positive gate voltages. This resulted in an unprecedented reduction in I(off), as the sub-10 nm sized nanoclusters acted as numerous tunable valves, providing greatly improved network sensitivity to gate voltages in the relatively small range of ±10 V, increasing I(on)/I(off) by up to 205-fold. Larger nanoclusters were found to increase the network conductivity but decrease I(on)/I(off). The ability to convert metallic SWNTs to semiconducting without removing them allows for enhanced I(on) and lower noise while still achieving greatly enhanced magnitudes of I(on)/I(off).