Jiajia Xue

A Eutectic Mixture of Natural Fatty Acids Can Serve as the Gating Material for Near-Infrared-Triggered Drug Release

A smart release system responsive to near-infrared (NIR) light is developed for intracellular drug delivery. The concept is demonstrated by coencapsulating doxorubicin (DOX) (an anticancer drug) and IR780 iodide (IR780) (an NIR-absorbing dye) into nanoparticles made of a eutectic mixture of naturally occurring fatty acids. The eutectic mixture has a well-defined melting point at 39 °C, and can be used as a biocompatible phase-change material for NIR-triggered drug release. The resultant nanoparticles exhibit prominent photothermal effect and quick drug release in response to NIR irradiation. Fluorescence microscopy analysis indicates that the DOX trapped in the nanoparticles can be efficiently released into the cytosol under NIR irradiation, resulting in enhanced anticancer activity. A new platform is thus offered for designing effective intracellular drug-release systems, holding great promise for future cancer therapy.

Differentiation of Bone Marrow Stem Cells into Schwann Cells for the Promotion of Neurite Outgrowth on Electrospun Fibers

Seeding nerve guidance conduits with Schwann cells can improve the outcome of peripheral nerve injury repair. Bone marrow stem cells (BMSCs) represent a good choice of cell source as they can differentiate into Schwann cells under appropriate conditions. In this work, we systematically investigated the differentiation of BMSCs into Schwann cells on scaffolds comprising electrospun fibers. We changed the alignment, diameter, and surface properties of the fibers to optimize the differentiation efficiency. The uniaxial alignment of fibers not only promoted the differentiation of BMSCs into Schwann cells but also dictated the morphology and alignment of the derived cells. Coating the surface of aligned fibers with laminin further enhanced the differentiation and thus increased the secretion of neurotrophins. When co-cultured with PC12 cells or chick dorsal root ganglion, the as-derived Schwann cells were able to promote the outgrowth of neurites from cell bodies and direct their extension along the fibers, demonstrating the positive impacts of both the neurotrophic effect and the morphological contact guidance. This work offers a promising strategy for integrating fiber guidance with stem cell therapy to augment peripheral nerve injury repair.

Reconstitution of Low-Density Lipoproteins with Fatty Acids for the Targeted Delivery of Drugs into Cancer Cells

Low-density lipoproteins (LDLs) are a class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. A facile procedure is used for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts. According to a hypothesized mechanism, the reconstituted LDLs can also enable metabolism-triggered drug release while preventing the payloads from lysosomal degradation. This study demonstrates that LDLs reconstructed with fatty acids hold great promise to serve as effective and versatile nanocarriers for targeted cancer therapy.

Enhancing the Mechanical Properties of Electrospun Nanofiber Mats through Controllable Welding at the Cross Points

This communication describes a simple and effective method for welding electrospun nanofibers at the cross points to enhance the mechanical properties of their nonwoven mats. The welding is achieved by placing a nonwoven mat of the nanofibers in a capped vial with the vapor of a proper solvent. For polycaprolactone (PCL) nanofibers, the solvent is dichloromethane (DCM). The welding can be managed in a controllable fashion by simply varying the partial pressure of DCM and/or the exposure time. Relative to the pristine nanofiber mat, the mechanical strength of the welded PCL nanofiber mat can be increased by as much as 200%. Meanwhile, such a treatment does not cause any major structural changes, including morphology, fiber diameter, and pore size. This study provides a generic method for improving the mechanical properties of nonwoven nanofiber mats, holding great potential in various applications.

Micropatterning of the Ferroelectric Phase in a Poly(vinylidene difluoride) Film by Plasmonic Heating with Gold Nanocages

Polymer thin films with patterned ferroelectric domains are attractive for a broad range of applications, including the fabrication of tactile sensors, infrared detectors, and non-volatile memories. Herein, we report the use of gold nanocages (AuNCs) as plasmonic nanostructures to induce a ferroelectric-paraelectric phase transition in a poly(vinylidene fluoride) (PVDF) thin film by leveraging its photothermal effect. This technique allows us to generate patterned domains of ferroelectric PVDF within just a few seconds. The incorporation of AuNCs significantly enhances the pyroelectric response of the ferroelectric film under near-infrared irradiation. We also demonstrate the use of such patterned ferroelectric films for near-infrared sensing/imaging.

Micropatterned Polymer Nanorod Forests and Their Use for Dual Drug Loading and Regulation of Cell Adhesion

This paper describes a simple method for the fabrication of micropatterned polymer nanorod forests by templating against the channels in an anodized aluminum oxide membrane partially masked by gelatin. The nanorod forests easily support bimodal drug loading, with one drug encapsulated in the nanorods and the other physisorbed on their surface. During cell culture, preosteoblasts are predominantly attracted to the nanorod forests and driven to climb up along the nanorods. This type of scaffold integrates both microscale and nanoscale features into a single substrate, holding great potential for applications in cell culture and tissue engineering.

Nanofiber-Based Multi-Tubular Conduits with a Honeycomb Structure for Potential Application in Peripheral Nerve Repair

Peripheral nerve injury is a large-scale problem and it is a great challenge to repair the long lesion in a thick nerve. The design of a multi-tubular conduit with a honeycomb structure by mimicking the anatomy of a peripheral nerve for the potential repair of large defects in thick nerves has been reported. A bilayer mat of electrospun nanofibers is rolled up to form a single tube, with the inner and outer layers comprised aligned and random nanofibers, respectively. Seven such tubes are then assembled into a hexagonal array and encased within the lumen of a larger tube to form the multi-tubular conduit. By introducing an adhesive to the regions between the tubes, the conduit is robust enough for handling during surgery. The seeded bone marrow stem cells (BMSCs) are able to proliferate in all the tubes with even circumferential and longitudinal distributions. Under chemical induction, the BMSCs are transdifferentiated into Schwann-like cells in all the tubes. While the cellular version holds great promise for peripheral nerve repair, the multi-tubular conduit can also be used to investigate the fundamental aspects involved in the development of peripheral nervous system and migration of cells.

General Method for Generating Circular Gradients of Active Proteins on Nanofiber Scaffolds Sought for Wound Closure and Related Applications

Scaffolds functionalized with circular gradients of active proteins are attractive for tissue regeneration because of their enhanced capability to accelerate cell migration and/or promote neurite extension in a radial fashion. Here, we report a general method for generating circular gradients of active proteins on scaffolds composed of radially aligned nanofibers. In a typical process, the scaffold, with its central portion raised using a copper wire to take a cone shape, was placed in a container (upright or up-side-down), followed by dropwise addition of bovine serum albumin (BSA) solution into the container. As such, a circular gradient of BSA was generated along each nanofiber. The bare regions uncovered by BSA were then filled with an active protein of interest. In demonstrating their potential applications, we used different model systems to examine the effects of two types of protein gradients. While the gradient of laminin and epidermal growth factor accelerated the migration of fibroblasts and keratinocytes, respectively, from the periphery toward the center of the scaffold, the gradient of nerve growth factor promoted the radial extension of neurites from the embryonic chick dorsal root ganglion. This method for generating circular gradients of active proteins can be readily extended to different types of scaffolds to suit wound closure and related applications that involve cell migration and/or neurite extension in a radial fashion.