Biocompatible polymers have been extensively applied to molecular assembly techniques on a micro- and nanoscale to miniaturize functional devices for biomedical uses. However, cytotoxic assessments of developed devices are prone to partially focus on non-specific cells or cells associated with the specific applications. Thereby, since toxicity is dependent on the type of cells and protocols, we do not fully understand the relative toxicities of polymers. Additionally, we need to ensure the blood cell biocompatibility of developed devices prior to that of targeted cells because most of the devices contact the blood before reaching the targeted regions. Motivated by this issue, we focused on screening cytotoxicity of polymers widely used for the layer-by-layer assembly technique using human blood cells. Cytotoxicity at the early stage was investigated on twenty types of polymers (positively charged, negatively charged, or neutral) and ten combination forms via hemolysis, cell viability, and AnnexinV-FITC/PI staining assays. We determined their effects on the cell membrane depending on their surface chemistry by molecular dynamics simulations. Furthermore, the toxicity of LbL-assembled nanofilms was assessed by measuring cell viability. Based on this report, researchers can produce nanofilms that are better suited for drug delivery and biomedical applications by reducing the possible cytotoxicity.

The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

Exogeneous nitric oxide (NO) delivery is a promising therapeutic method because NO is a significant cell signaling molecule to control physiological functions. A major challenge for NO delivery is to control release due to the fast diffusion properties of gaseous molecules with low molecular weight. It is important in biomedical applications to mitigate initial burst emissions because higher concentrations of reactive NO cause cytotoxicity and tissue damage. In this study, a nanoparticle system is developed to control spontaneous gas release on the basis of surface-modified silica nanoparticles (Si NPs) by branched polyethylene imine (BPEI). BPEI is not only a scaffold of N-diazeniumdiolatesa type of NO donorand but also a stabilizer of donors by molecular interactions with nearby amine groups. With the sustained-release manner, BPEI-coated NO-releasing Si NPs (BPEI-NO NPs) have multifunctional properties, including bactericidal efficacies as well as good cell viability for human cells. An improved ocular wound recovery is achieved in the mouse keratitis model. This study demonstrates the great potential of the NO-releasing NP as a multifunctional nanotherapeutic in biomedical applications.

Ocular drug delivery is an interesting field in current research. Silica nanoparticles (SiNPs) are promising drug carriers for ophthalmic drug delivery. However, little is known about the toxicity of SiNPs on ocular surface cells such as human corneal epithelial cells (HCECs). In this study, we evaluated the cytotoxicity induced by 50, 100 and 150 nm sizes of SiNPs on cultured HCECs for up to 48 hours. SiNPs were up-taken by HCECs inside cytoplasmic vacuoles. Cellular reactive oxygen species generation was mildly elevated, dose dependently, with SiNPs, but no significant decrease of cellular viability was observed up to concentrations of 100 μg/ml for three different sized SiNPs. Western blot assays revealed that both cellular autophagy and mammalian target of rapamycin (mTOR) pathways were activated with the addition of SiNPs. Our findings suggested that 50, 100 and 150 nm sized SiNPs did not induce significant cytotoxicity in cultured HCECs.

A superhydrophobic carbon nanofiber network inlay-gated mesh with high durability and separation performance was developed for oil–water emulsion separation.

The separation of oil–water mixtures using superwetting membranes is increasingly desired, particularly for the practical processes of environmental protection and industrial production. However, achieving durability and multifunction in current separation systems, among other issues, remains challenging. Herein, a cobweb-inspired gating multiscale pore-based membrane has been created as the framework system for removing emulsified water from an oil phase. This membrane was assembled using macroscale chemically etched stainless steel mesh (ESSM), a microscale network of carbon nanofibers (CNFs), and a nanoscale network of single-walled carbon nanotubes (SWCNTs). Superhydrophobic and superoleophilic interfaces were then fabricated on the ESSM/CNFs–SWCNTs gating membrane using a polydimethylsiloxane (PDMS) coating. The ability of this membrane with a discrete water-repellent property to resist mechanical damage was demonstrated in gravity-driven water-in-oil emulsion separation with high performance; this behavior was attributed to the protective metal mesh and different pore scales resulting from the embedded dual-scale network structure. As a result, this smart superwetting membrane structure can serve as a novel platform for constructing a multifunctional emulsified oil–water separation system with high robustness. Moreover, on the basis of the findings in this study, current filter membranes fabricated using a fibrous network can be improved to achieve higher durability.

To utilize potentials of nitric oxide (NO) gas in anti-bacterial, anticancer, wound healing applications, numerous studies have been conducted to develop a NO delivery system in the past few decades. Even though a coating method and film types are essential to apply in biomedical device coating from previous NO delivery systems, release control from the coating system is still challenging. In this study, we introduced a multilayered polymeric coating system to overcome the uncontrollable NO release kinetics of film systems. We used biocompatible gelatin and tannic acid to construct a rough, porous structured film based on the layer-by-layer self-assembly method. The multilayered polymeric structure facilitated the controlled amount of NO release from (Gel/TA) n film and showed burst release in early period owing to their large surface area from the rough, porous structure. We synthesized the proton-responsive NO donor, N- diazeniumdiolate (NONOates), into the (Gel/TA) n film through a chemical reaction under high pressure NO gas. NO release profile was analyzed by a real-time NO analysis machine (NOA 280i). Then, the NO-releasing (Gel/TA) n film was tested its toxicity against human dermal fibroblast cells and bactericidal effects against Staphylococcus aureus .

One important aspect of nanotechnology includes thin films capable of being applied to a wide variety of surfaces. Indispensable functions of films include controlled surface energy, stability, and biocompatibility in physiological systems. In this study, we explored the ancient Asian coating material "lacquer" to enhance the physiological and mechanical stability of nanofilms. Lacquer is extracted from the lacquer tree and its main component called urushiol, which is a small molecule that can produce an extremely strong coating. Taking full advantage of layer-by-layer assembly techniques, we successfully fabricated urushiol-based thin films composed of small molecule/polymer multilayers by controlling their molecular interaction. Unique cairnlike nanostructures in this film, produced by urushiol particles, have advantages of intrinsic hydrophobicity and durability against mechanical stimuli at physiological environment. We demonstrated the stability tests as well as the antimicrobial effects of this film.