Polymer Pen Lithography with Lipids for Large-Area Gradient Patterns.

Gradient patterns comprising bioactive compounds over comparably (in regard to a cell size) large areas are key for many applications in the biomedical sector, in particular, for cell screening assays, guidance, and migration experiments. Polymer pen lithography (PPL) as an inherent highly parallel and large area technique has a great potential to serve in the fabrication of such patterns. We present strategies for the printing of functional phospholipid patterns via PPL that provide tunable feature size and feature density gradients over surface areas of several square millimeters. By controlling the printing parameters, two transfer modes can be achieved. Each of these modes leads to different feature morphologies. By increasing the force applied to the elastomeric pens, which increases the tip-surface contact area and boosts the ink delivery rate, a switch between a dip-pen nanolithography (DPN) and a microcontact printing (µCP) transfer mode can be induced. A careful inking procedure ensuring a homogeneous and not-too-high ink-load on the PPL stamp ensures a membrane-spreading dominated transfer mode, which, used in combination with smooth and hydrophilic substrates, generates features with constant height, independently of the applied force of the pens. Ultimately, this allows us to obtain a gradient of feature sizes over a mm2 substrate, all having the same height on the order of that of a biological cellular membrane. These strategies allow the construction of membrane structures by direct transfer of the lipid mixture to the substrate, without requiring previous substrate functionalization, in contrast to other molecular inks, where structure is directly determined by the printing process itself. The patterns are demonstrated to be viable for subsequent protein binding, therefore adding to a flexible feature library when gradients of protein presentation are desired.

Development of Anisotropic Electrically Conductive GNP-Reinforced PCL-Collagen Scaffold for Enhanced Neurogenic Differentiation under Electrical Stimulation.

The internal electric field of the human body plays a crucial role in regulating various biological processes, such as, cellular interactions, embryonic development and the healing process. Electrical stimulation (ES) modulates cytoskeleton and calcium ion activities to restore nervous system functioning. When exposed to electrical fields, stem cells respond similarly to neurons, muscle cells, blood vessel linings, and connective tissue (fibroblasts), depending on their environment. This study develops cost-effective electroconductive scaffolds for regenerative therapy. This was achieved by incorporating carboxy functionalized graphene nanoplatelets (GNPs) into a Polycaprolactone (PCL)-collagen matrix. ES was used to assess the scaffolds' propensity to boost neuronal differentiation from MSCs. This study reported that aligned GNP-reinforced PCL-Collagen scaffolds demonstrate substantial MSC differentiation with ES. This work effectively develops scaffolds using a simple, cost-effective synthesis approach. The direct coupling approach generated a homogeneous electric field to stimulate cells cultured on GNP-reinforced scaffolds. The scaffolds exhibited improved mechanical and electrical characteristics, as a result of the reinforcement with carbon nanofillers. In vitro results suggest that electrical stimulation helps differentiation of mesenchymal stem-like cells (MSC-like) towards neuronal. This finding holds great potential for the development of effective treatments for tissue injuries related to the nervous system.

4D Printed Programmable Shape-Morphing Hydrogels as Intraoperative Self-Folding Nerve Conduits for Sutureless Neurorrhaphy.

There are only a few reports of implantable 4D printed biomaterials, most of which exhibit slow deformations rendering them unsuitable for in situ surgical deployment. In this study, a hydrogel system is engineered with defined swelling behaviors, which demonstrated excellent printability in extrusion-based 3D printing and programmed shape deformations post-printing. Shape deformations of the spatially patterned hydrogels with defined infill angles are computationally predicted for a variety of 3D printed structures, which are subsequently validated experimentally. The gels are coated with gelatin-rich nanofibers to augment cell growth. 3D-printed hydrogel sheets with pre-programmed infill patterns rapidly self-rolled into tubes in vivo to serve as nerve-guiding conduits for repairing sciatic nerve defects in a rat model. These 4D-printed hydrogels minimized the complexity of surgeries by tightly clamping the resected ends of the nerves to assist in the healing of peripheral nerve damage, as revealed by histological evaluation and functional assessments for up to 45 days. This work demonstrates that 3D-printed hydrogels can be designed for programmed shape changes by swelling in vivo to yield 4D-printed tissue constructs for the repair of peripheral nerve damage with the potential to be extended in other areas of regenerative medicine.

Tongue hyperpigmentation resulting from peginterferon alfa-2b and ribavirin treatment in a patient with chronic hepatitis C.

Hepatitis C virus (HCV) infection has been associated with several cutaneous diseases such as lichen planus, porphyria cutanea tarda, chronic pruritus, and cutaneous necrotizing vasculitis (Doutre, Arch Dermatol 135:1401-1403, 1999). The antiviral treatment for chronic HCV with interferon alfa (INF) or peginterferon alfa (PEG-INF) combined with rivabirin also leads to many skin side effects including injection site reaction, generalized skin rashes, pruritus, dry skin, alopecia, and exacerbation of autoimmune processes, particularly psoriasis, lichen planus or vitiligo (Dalekos et al., Eur J Gastroenterol Hepatol 10:933-939, 1998; Sookoian et al., Arch Dermatol 135:1000-1000, 1999). There are case reports of tongue hyperpigmentation during combination therapy of PEG IFN and RBV in chronic hepatitis C both in dark-skined as well as Caucasian. We report the first case of tongue hyperpigmentation associated with PEG-INF-2b plus ribavirin administration in a non-Caucasian patient with genotype 4.

Enhanced neurogenic differentiation on anisotropically conductive carbon nanotube reinforced polycaprolactone-collagen scaffold by applying direct coupling electrical stimulation.

Electrical stimulation is conducive to neural regeneration. Different types of stimuli propagation patterns are required for regenerating cells in peripheral and central nervous systems. Modulation of the pattern of stimuli propagation cannot be achieved through external means. Reinforcing scaffolds, with suitably shaped conductive second phase materials, is a promising option in this regard. The present study has taken the effort of modulating the pattern (arrangement) of reinforced phase, namely multiwalled carbon nanotubes (MWCNT), in a biodegradable scaffold made of PCL-collagen mixture, by applying an external electric field during curing. Because of their extraordinary physical properties, MWCNTs have been selected as nano-reinforcement for this study. The nature of reinforcement affects the electrical conductivity of the scaffold and also determines the type of cell it can support for regeneration. Further, electrical stimulation, applied during incubation, was observed to have a positive influence on differentiating neural cells in vitro. However, the structure of the nano-reinforcement determined the differentiated morphology of the cells. Reinforced MWCNTs being tubes, imparted bipolarity to the cells. Therefore, these scaffolds, coupled with electrical stimulation possess significant potential to be used for directional regeneration of the nerves.

Alloyed Thermoelectric PbTe-SnTe Films Formed via Aerosol Deposition.

The discovery of new thermoelectric materials has the potential to benefit from advances in high-throughput methodologies. Traditional synthesis and characterization routes for thermoelectrics are time-consuming serial processes. In contrast, high-throughput materials discovery is commonly done by thin film growth, which may produce microstructures that are metastable or compositionally graded and, therefore, are challenging to characterize. As a middle ground between bulk synthesis and thin film deposition, we find that the aerosol deposition process can rapidly produce samples that exhibit electronic property trends consistent with those produced by traditional bulk means. We demonstrate rapid growth of discrete thermoelectric thick films of varying chemical compositions (Pb1-xSnxTe) from PbTe and SnTe polydisperse micrometer sized powder feedstocks. The high deposition rate (near 1 µm min-1) and resultant microstructures are advantageous as the diffusion length scales promote rapid thermal treatment and equilibrium phase formation. Room-temperature high-throughput measurements of the Seebeck coefficient and resistivity are compared to traditionally produced bulk materials. The Seebeck coefficient of the films follows the trends of traditional samples, but the resistivity is found to be more sensitive to microstructural effects. Ultimately, we demonstrate a framework for exploratory materials science using aerosol deposition and high-throughput characterization instrumentation.

Comparative study on the efficacy of the UHMWPE surface modification by chemical etching and electrostatic spraying method for drug release by orthopedic implants.

Failure of fixation between bone and implant surface due to bacterial infection, is one of the key challenges in total hip arthroplasty. It might lead to poor implant stability and complex revision surgery. Surface modification of an acetabular cup liner for sustained drug delivery is an effective approach to reduce the biofilms associated infection. The aim of the study is to evaluate the influence of different surface modification technique on drug delivery, mechanical and tribological performances of the acetabular cup liner. Solvent-based etching and electrostatic spray deposition technique was individually used to engineer a thin microporous surface layer on ultra-high molecular weight polyethylene (UHMWPE), which is commercially used as acetabular cup liner in total hip implant. Porous surfaces were filled with drug (gentamicin) containing biodegradable polymer (chitosan) through impregnation process and their efficacy was compared in the intended application. The surfaces, modified by both techniques, have shown lower friction coefficient. The higher wear rates were noticed for electrostatic sprayed coating. Both the modified surfaces have shown slight decrease in hardness and elastic modulus, which may be attributed to improper impregnation of polymer inside porous surface. However, after the release of drug, the solvent-based etched surface regains its mechanical and tribological properties, in similar range to the unmodified UHMWPE surface. Both the modified surfaces have shown an impressive drug release profile and in vitro antibacterial efficacy. The drug release duration was more for electrostatic spray modified surface. Hence, these surfaces modified implant parts shown great promise for fighting against post-surgery bacterial infection.