Chunlei Zhu

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.

Inverse Opal Scaffolds and Their Biomedical Applications

Three-dimensional porous scaffolds play a pivotal role in tissue engineering and regenerative medicine by functioning as biomimetic substrates to manipulate cellular behaviors. While many techniques have been developed to fabricate porous scaffolds, most of them rely on stochastic processes that typically result in scaffolds with pores uncontrolled in terms of size, structure, and interconnectivity, greatly limiting their use in tissue regeneration. Inverse opal scaffolds, in contrast, possess uniform pores inheriting from the template comprised of a closely packed lattice of monodispersed microspheres. The key parameters of such scaffolds, including architecture, pore structure, porosity, and interconnectivity, can all be made uniform across the same sample and among different samples. In conjunction with a tight control over pore sizes, inverse opal scaffolds have found widespread use in biomedical applications. In this review, we provide a detailed discussion on this new class of advanced materials. After a brief introduction to their history and fabrication, we highlight the unique advantages of inverse opal scaffolds over their non-uniform counterparts. We then showcase their broad applications in tissue engineering and regenerative medicine, followed by a summary and perspective on future directions.

Surgical Sutures with Porous Sheaths for the Sustained Release of Growth Factors.

Surgical sutures with highly porous sheaths are developed using a swelling and freeze-drying procedure without compromising their mechanical properties. The modified sutures show a high capacity for loading biofactors and are able to release the loaded biofactors in a sustained manner.

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.

Design and Fabrication of a Hierarchically Structured Scaffold for Tendon‐to‐Bone Repair

A hierarchically structured scaffold is designed and fabricated for facilitating tendon-to-bone repair. The scaffold is composed of three regions with distinct functions: (i) an array of channels to guide the in-growth of cells and aligned deposition of collagen fibers, as well as integration of the scaffold with the tendon side, (ii) a region with a gradient in mineral composition to facilitate stress transfer between tendon and bone, and (iii) a mineralized inverse opal region to promote the integration of the scaffold with the underlying bone. Cell culture experiments confirm that adipose-derived stromal cells are able to infiltrate and proliferate through the entire thickness of the scaffold without compromised cell viability. The seeded stem cells exhibit directed differentiation into tenocytes and osteoblasts along the mineral gradient as a response to the gradient in Youngs modulus. This novel scaffold holds great promise to promote the formation of a functional tendon-to-bone attachment by offering a structurally and compositionally appropriate microenvironment for healing.

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.

Combination cancer treatment through photothermally controlled release of selenous acid from gold nanocages

Selenite, one of the inorganic forms of selenium, is emerging as an attractive chemotherapeutic agent owing to its selectivity in eradicating cancer cells. Here we demonstrate a new formulation of nanomedicine based on selenous acid, which is mixed with lauric acid (a phase-change material with a melting point around 43 °C) and then loaded into the cavities of Au nanocages. The Au nanocages can serve as a carrier during cell endocytosis and then as a photothermal agent to melt the lauric acid upon the irradiation with a near-infrared laser, triggering the swift release of selenous acid. The photothermal and chemo therapies can also work synergistically, leading to enhanced destruction of cancer cells relative to normal cells. Our systematic study suggests that the impaired mitochondrial function arising from the ROS generated through combination treatment is responsible for the cell death. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.

Inverse Opal Scaffolds with Gradations in Mineral Content for Spatial Control of Osteogenesis

The design and fabrication of inverse opal scaffolds with gradations in mineral content to achieve spatial control of osteogenesis are described. The gradient in mineral content is established via the diffusion-limited transport of hydroxyapatite nanoparticles in a closely packed lattice of gelatin microbeads. The mineral-graded scaffold has an array of uniform pores and interconnected windows to facilitate efficient transport of nutrients and metabolic wastes, ensuring high cell viability. The graded distribution of mineral content can provide biochemical and mechanical cues for spatially regulating the osteogenic differentiation of adipose-derived stromal cells. This new class of scaffolds holds promise for engineering the interfaces between mineralized and unmineralized tissues.

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.