Cell membrane-biomimetic coating via click-mediated liposome fusion for mitigating the foreign-body reaction.

The foreign-body reaction (FBR) caused by the implantation of synthetic polymer scaffolds seriously affects tissue-biomaterial integration and tissue repair. To address this issue, we developed a cell membrane-biomimetic coating formed by "click"-mediated liposome immobilization and fusion on the surface of electrospun fibers to mitigate the FBR. Utilization of electrospun polystyrene microfibrous scaffold as a model matrix, we deposited azide-incorporated silk fibroin on the surface of the fibers by the layer-by-layer assembly, finally, covalently modified with clickable liposomes via copper-free SPAAC click reaction. Compared with physical adsorption, liposomes click covalently binding can quickly fuse to form lipid film and maintain fluidity, which also improved liposome stability in vitro and in vivo. Molecular dynamics simulation proved that "click" improves the binding rate and strength of liposome to silk substrate. Importantly, histological observation and in vivo fluorescent probes imaging showed that liposome-functionalized electrospun fibers had negligible characteristics of the FBR and were accompanied by many infiltrated host cells and new blood vessels. We believe that the promotion of macrophage polarization toward a pro-regenerative phenotype plays an important role in vascularization. This bioinspired strategy paves the way for utilizing cell membrane biomimetic coating to resist the FBR and promote tissue-scaffold integration.

MSC-derived immunomodulatory extracellular matrix functionalized electrospun fibers for mitigating foreign-body reaction and tendon adhesion.

Adhesion formation during tendon healing remains a severe problem in clinical practice. Multiple factors contribute to postoperative adhesion formation, and macrophage-driven inflammation is thought to be greatly involved in this process. We hypothesize that reducing macrophage-mediated inflammation in the injured tendon by regulating M1 to M2 macrophage polarization may effectively inhibit adhesion formation. Here, we developed an acellular immunomodulatory biomaterial consisting of an electrospun polycaprolactone/silk fibroin (PCL/SF) composite fibrous scaffold functionalized with mesenchymal stem cell (MSC)-derived extracellular matrix (ECM). To enhance the immunoregulatory potential of MSCs, we performed inflammatory licensing with IFN-γ to obtain immunomodulatory ECM (iECM). Proteomic analyses of MSCs and their secreted ECM components from different culture conditions revealed the MSC-ECM molecular signatures and the potential mechanism of ECM immunoregulation. Then, the immunoregulatory potential of the iECM-modified scaffold was evaluated in vitro and in vivo. Relative to the PCL/SF fibrous scaffold, the iECM-functionalized scaffold facilitated M2 macrophage polarization and inhibited the expression of multiple cytokines (IL-1ß, IL-6, CXCL11, IL-10, IL-1R2, and TGF-ß1) in vitro, strongly suggesting the immunosuppressive ability of iECM derived from inflammatory licensed MSCs. Consistent with the in vitro findings, the results of rat subcutaneous implantation indicated that a markedly lower foreign-body reaction (FBR) was obtained in the PCL/SF-iECM group than in the other groups, as evidenced by thinner fibrotic capsule formation, less type I collagen production and more M2-type macrophage polarization. In the rat Achilles tendon injury model, the PCL/SF-iECM scaffold greatly mitigated tendon adhesion with clear sheath space formation between the tendon and the scaffold. These data highlight the immunomodulatory potential of iECM-functionalized fibrous scaffolds to attenuate FBR by modulating M2 macrophage polarization, thereby preventing tendon adhesion. STATEMENT OF SIGNIFICANCE: Electrospun PCL/SF fibrous scaffolds functionalized with ECM secreted by MSCs stimulated by inflammatory factor IFN-γ was developed that combined physical barrier and immunomodulatory functions to prevent tendon adhesion formation. PCL/SF micro-nanoscale bimodal fibrous scaffolds prepared by emulsion electrospinning possess high porosity and a large pore size beneficial for nutrient transport to promote intrinsic healing; moreover, surface modification with immunomodulatory ECM (iECM) mitigates the FBR of fibrous scaffolds to prevent tendon adhesion. The iECM-functionalized electrospun scaffolds exhibit powerful immunomodulatory potency in vitro and in vivo. Moreover, the iECM-modified scaffolds, as an anti-adhesion physical barrier with immunomodulatory ability, have an excellent performance in a rat Achilles tendon adhesion model. MSC secretome-based therapeutics, as an acellular regenerative medicine strategy, are expected to be applied to other inflammatory diseases due to its strong immunoregulatory potential.

Surface modification of electrospun fibers with mechano-growth factor for mitigating the foreign-body reaction.

The implantation of synthetic polymeric scaffolds induced foreign-body reaction (FBR) seriously influence the wound healing and impair functionality recovery. A novel short peptide, mechano-growth factor (MGF), was introduced in this study to modify an electrospun polycaprolactone (PCL) fibrous scaffold to direct the macrophage phenotype transition and mitigate the FBR. In vitro studies discovered the cell signal transduction mechanism of MGF regulates the macrophage polarization via the expression of related genes and proteins. We found that macrophages response the MGF stimuli via endocytosis, then MGF promotes the histone acetylation and upregulates the STAT6 expression to direct an anti-inflammatory phenotype transition. Subsequently, an immunoregulatory electrospun PCL fibrous scaffold was modified by silk fibroin (SF) single-component layer-by-layer assembly, and the SF was decorated with MGF via click chemistry. Macrophages seeded on scaffold to identify the function of MGF modified scaffold in directing macrophage polarization in vitro. Parallelly, rat subcutaneous implantation model and rat tendon adhesion model were performed to detect the immunomodulatory ability of the MGF-modified scaffold in vivo. The results demonstrate that MGF-modified scaffold is beneficial to the transformation of macrophages to M2 phenotype in vitro. More importantly, MGF-functionalized scaffold can inhibit the FBR at the subcutaneous tissue and prevent tissue adhesion.

Author Correction: Sensitivity enhancement of flexible gas sensors via conversion of inkjet-printed silver electrodes into porous gold counterparts.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Sensitivity enhancement of flexible gas sensors via conversion of inkjet-printed silver electrodes into porous gold counterparts.

This work describes a facile, mild and general wet chemical method to change the material and the geometry of inkjet-printed interdigitated electrodes (IDEs) thus drastically enhancing the sensitivity of chemiresistive sensors. A novel layer-by-layer chemical method was developed and used to uniformly deposit semiconducting single-wall carbon nanotube (SWCNT)-based sensing elements on a Kapton® substrate. Flexible chemiresistive sensors were then fabricated by inkjet-printing fine-featured silver IDEs on top of the sensing elements. A mild and facile two-step process was employed to convert the inkjet-printed dense silver IDEs into their highly porous gold counterparts under ambient conditions without losing the IDE-substrate adhesion. A proof-of-concept gas sensor equipped with the resulting porous gold IDEs featured a sensitivity to diethyl ethylphosphonate (DEEP, a simulant of the nerve agent sarin) of at least 5 times higher than a similar sensor equipped with the original dense silver IDEs, which suggested that the electrode material and/or the Schottky contacts between the electrodes and the SWCNTs might have played an important role in the gas sensing process.

A bio-enabled maximally mild layer-by-layer Kapton surface modification approach for the fabrication of all-inkjet-printed flexible electronic devices.

A bio-enabled, environmentally-friendly, and maximally mild layer-by-layer approach has been developed to surface modify inherently hydrophobic Kapton HN substrates to allow for great printability of both water- and organic solvent-based inks thus facilitating the full-inkjet-printing of flexible electronic devices. Different from the traditional Kapton surface modification approaches which are structure-compromising and use harsh conditions to target, and oxidize and/or remove part of, the surface polyimide of Kapton, the present Kapton surface modification approach targeted the surface electric charges borne by its additive particles, and was not only the first to utilize environmentally-friendly clinical biomolecules to build up a thin film of protamine-heparin complex on Kapton, but also the first to be conducted under minimally destructive and maximally mild conditions. Besides, for electrically charged ink particles, the present surface modification method can enhance the uniformity of the inkjet-printed films by reducing the "coffee ring effect". As a proof-of-concept demonstration, reduced graphene oxide-based gas sensors, which were flexible, ultra-lightweight, and miniature-sized, were fully-inkjet-printed on surface modified Kapton HN films and tested for their sensitivity to dimethyl methylphosphonate (a nerve agent simulant). Such fabricated sensors survived a Scotch-tape peel test and were found insensitive to repeated bending to a small 0.5 cm radius.

Fully inkjet-printed microfluidics: a solution to low-cost rapid three-dimensional microfluidics fabrication with numerous electrical and sensing applications.

As the needs for low-cost rapidly-produced microfluidics are growing with the trend of Lab-on-a-Chip and distributed healthcare, the fully inkjet-printing of microfluidics can be a solution to it with numerous potential electrical and sensing applications. Inkjet-printing is an additive manufacturing technique featuring no material waste and a low equipment cost. Moreover, similar to other additive manufacturing techniques, inkjet-printing is easy to learn and has a high fabrication speed, while it offers generally a great planar resolution down to below 20 µm and enables flexible designs due to its inherent thin film deposition capabilities. Due to the thin film feature, the printed objects also usually obtain a high vertical resolution (such as 4.6 µm). This paper introduces a low-cost rapid three-dimensional fabrication process of microfluidics, that relies entirely on an inkjet-printer based single platform and can be implemented directly on top of virtually any substrates.

Inverted polymer solar cells with amorphous indium zinc oxide as the electron-collecting electrode.

We report on the fabrication and performance of polymer-based inverted solar cells utilizing amorphous indium zinc oxide (a-IZO) as the electron-collecting electrode. Amorphous IZO films of 200 nm thickness were deposited by room temperature sputtering in a high-purity argon atmosphere. The films possessed a high optical transmittance in the visible region (≥ 80%), a low resistivity (3.3 × 10⁻4 Ωcm), a low surface roughness (root mean square = 0.68 nm), and a low work function (4.46 ± 0.02 eV). Inverted solar cells with the structure a-IZO/P3HT: PCBM/PEDOT:PSS/Ag exhibited a power conversion efficiency of 3% estimated for AM 1.5G, 100 mW/cm² illumination.

Rapid bioenabled formation of ferroelectric BaTiO3 at room temperature from an aqueous salt solution at near neutral pH.

A 12-mer peptide, identified through phage display biopanning, has been used for the first time to induce the rapid formation of ferroelectric (tetragonal) nanocrystalline BaTiO3 at room temperature from an aqueous salt precursor solution at near neutral pH. BaTiO3 is widely used in capacitors, thermistors, displays, and sensors owing to its attractive dielectric, ferroelectric, pyroelectric, optical, and electrochemical properties. Two 12-mer peptides (BT1 and BT2) were selected from a phage-displayed peptide library via binding to tetragonal BaTiO3 powder. While these peptides possessed various types of amino acids, 8 of the 12 amino acids were common to both peptides. Each of these peptides induced the formation of faceted nanoparticles (50-100 nm diameter) from an aqueous precursor solution. X-ray diffraction and selected area electron diffraction patterns obtained from these faceted nanoparticles were consistent with the BaTiO3 compound. Rietveld analyses of the X-ray diffraction patterns yielded good fits to tetragonal crystal structures, with the BaTiO3 formed in the presence of the BT2 peptide exhibiting the most tetragonal character. A coating of the latter BaTiO3 nanoparticles exhibited polarization hysteresis (a well-known characteristic of ferroelectric materials) at room temperature and a relative permittivity of 2200. Such rapid, peptide-induced precipitation at room temperature provides new opportunities for direct BaTiO3 formation on low-melting or reactive materials (e.g., plastics, cloths, bio-organics) and the low temperature integration of BaTiO3 into electronic devices (e.g., on silicon or flexible polymer substrates).

Structural changes accompanying human serum albumin's binding of fatty acids are concerted.

Long chain fatty acids (LCFAs), a major source of cellular energy, are solubilized and transported in the blood by binding to serum albumin. Changes in human serum albumin's (HSA's) UV absorption and characteristic reactivity with pyridoxal-5'-phosphate appear to reflect a concerted change in its structure upon binding five equivalents of myristate. Isothermal titrations with myristate and other LCFA anions are also consistent with the presence of five strong, interacting, binding sites. Although HSA is usually thought to have many independent LCFA anion binding sites, just five interacting sites appear to account for the changes in structure that accompany its binding of myristate.