Wen Zhong

Textiles and Human Skin, Microclimate, Cutaneous Reactions: An Overview

ABSTRACT This article overviews research in the interdisciplinary area of textile/skin interaction and related cutaneous intolerance. Microclimate in the skin/clothing system and especially the skin responses relates to the moisture and heat transfer within this system and plays a critical role in skin irritation from textiles. A discussion is then given on skin irritation reactions to textiles, including intolerance caused by chemicals (dyes and finishes) and physical contact/friction. Finally, two skin injuries, blisters and pressure ulcers, which are caused by physical contact, pressure, and friction, are documented. Despite the prevalent problems caused by ill textile/skin interactions, minimal efforts have been devoted to this field. In addition, the in vivo experimental studies infrequently lead to a solid conclusion. The cause may lie in the dramatic variation of skin conditions among individuals as well as among different anatomic sites of the same person. Another reason might be the lack of communications between researchers in the areas of textiles and dermatology.

Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

Schiff based injectable hydrogel for in situ pH-triggered delivery of doxorubicin for breast tumor treatment

In this study, we report a facile approach to develop an injectable hydrogel with an in situ and pH sensitive drug delivery system for cancer treatment. The hydrogel was based on modified chitosan and alginate. We conjugated doxorubicin (DOX) to succinated chitosan (S-chi) via a Schiff base between a ketone group in the DOX and an amine group in the S-chi, which led to a pH sensitive release of DOX upon the stimulus of an acidic tumor microenvironment. Hydrogel formed in minutes while DOX conjugated S-chi was mixed with oxidized alginate. The hydrogel structure was characterized by cryo-imaging, FTIR and a rheology test. The DOX release profiles were tested in response to different pH values. The MTT assay showed a low toxicity of the hydrogel. The gel in turn inhibited the growth of tumor cells MCF-7 effectively when loaded with DOX. Finally, the DOX laden hydrogel was injected into the xenograft breast tumor model and significantly inhibited tumor growth.

Mesenchymal stem cell-laden anti-inflammatory hydrogel enhances diabetic wound healing

The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.

Photo-cross-linked and pH-sensitive biodegradable micelles for doxorubicin delivery.

Cross-linked polymeric micelles have gained increasing research interest in the past decade due to the instability of existing polymeric micelles when used in vivo. In this study, we reported a series of covalently cross-linked pH-sensitive biodegradable micelles based on the poly(ethylene glycol)-hyperbranched poly(β-aminoester)s with acrylate group terminals (PEG-HBPAE-A) copolymers for intracellular delivery of doxorubicin (DOX). PEG-HBPAE-A can be self-assembled to form micellar nanoparticles in aqueous solution with diameters of approximately 160 nm. The non-cross-linked micelles (NCLMs) were cross-linked upon UV irradiation to form cross-linked micelles (CLMs). (1)H NMR, FT-IR and dynamic light scattering (DLS) were utilized to investigate the process of the UV cross-linking and the stability of CLMs. The results showed the significantly enhanced stability for CLMs in comparison to NCLMs. pH sensitivity of CLMs and NCLMs were also estimated by DLS. In vitro drug release studies confirmed that DOX release from DOX-loaded CLMs was greatly inhibited upon the neutral pH environment, whereas DOX underwent faster release in acidic conditions. MTT assays showed that DOX-loaded micelles had a similar inhibition rate for HepG-2 and MCF-7 cell lines compared with free DOX, whereas the blank CLMs and NCLMs showed very low cytotoxicity. Laser scanning confocal microscopy and real-time in situ fluorescence microscopy were exploited to investigate drug uptake in cells and drug distribution in the interior of cells. These results showed a promising nanocarrier for intracellular DOX delivery with great potential for cancer therapy.

Reducible self-assembled micelles for enhanced intracellular delivery of doxorubicin

This study developed novel reducible micelles that are approximately 100 nm in diameter and consist of poly(β-amino ester)-graft-poly(ethylene glycol) amphiphilic copolymers (PAE) with phenylbutylamine functional side groups. Our report is unique in the following ways: (1) the reductively degradable micelles provide a safe and efficient doxorubicin intracellular delivery, (2) the synthesis procedure is a simple and mild pathway with a well-defined structure, and (3) the aromatic phenylbutylamine side groups increase hydrophobicity and strengthen the interaction with doxorubicin (DOX) to improve the drug-loading capability. In vitro, micelles exhibit faster release of DOX upon the action of dithiothreitol (DTT). Drug-laden micelles present higher cell inhibition efficiency in comparison to free doxorubicin, while the blank micelles show very low cytotoxicity. The copolymeric micelles show a rapid internalization and efficient cytoplasmic doxorubicin release in both human hepatocellular carcinoma HepG2 and human breast adenocarcinoma MCF-7 cell lines observed by confocal laser scanning microscopy (CLSM). The micelle is promising for enhanced intracellular drug delivery in tumour cells.

Nanofibrous materials for wound care

Nanofibrous membranes are highly soft materials with high surface-to-volume ratios, and therefore can serve as excellent carriers for therapeutic agents that are antibacterial or accelerate wound healing. This article overviews research and development of nanofibrous dressing materials for wound care, in addition to a discussion of natural and synthetic polymers used in fabricating nanofibrous dressing materials, and a description of in vitro and in vivo evaluation methods for the performance and cytotoxicity of these materials. Natural polymers are usually believed to be less cytotoxic than synthetic polymer in wound care. However, most natural polymers exhibit relatively low mechanical strength than synthetic polymers. As a result, they are usually crosslinked or blended with synthetic polymers so as to somewhat affect their biocompatibility.

Polydopamine-coated paper-stack nanofibrous membranes enhancing adipose stem cells' adhesion and osteogenic differentiation

In the fabrication of 3-D complex tissues for implantation, layer-by-layer (LBL) electrospun nanofibrous scaffolds have recently received intensive interest. However, poor cell adhesion and cell expansion between the layers in an LBL stack remain important issues. In this study, we report a mussel-inspired, biomimetic approach to functionalize the surface of PCL/gelatin nanofibrous membranes coated with poly (dopamine) (PDA). Our study demonstrates that a PDA coating on electrospun PCL/gelatin nanofibers leads to a significant change in their surface properties and a higher adhesion force. Furthermore, we found that PDA coating promotes the adhesion and growth of adipose stem cells (ADSCs). In 3-D LBL stacked scaffolds, more cells survived in a PAD-coated scaffold than in a non-coated one. The PDA coating was further demonstrated to promote the osteogenic differentiation of ADSCs in LBL paper-stacking membranes. Our study suggests that PDA-coated paper-stacking nanofiber membranes present a facile and economic method for the development of 3D tissue engineering.

Cell-compatible hydrogels based on a multifunctional crosslinker with tunable stiffness for tissue engineering

This paper reports a functionalized cationic poly(amidoamine) crosslinker synthesized by Michael addition of peptide mimetic agmatine to N,N′-bis(acryloyl)cystamine. A polyethylene glycol diacrylate (PEGDA) hybrid hydrogel was developed using a functionalized crosslinker with cell adhesion capability and tunable stiffness. This engineered hydrogel presents a 3-D in-growth of cells and the cryosection shows remarkable morphology of the gel. The tunable stiffness of this hydrogel can regulate the osteogenic differentiation of mesenchymal stem cells from RT-PCR. Both in vitro and in vivo tests demonstrate adjustable degradation rate and biocompatibility. The crosslinker and its hydrogels hold promising potential for tissue engineering applications.

Polymeric mesoporous silica nanoparticles as a pH-responsive switch to control doxorubicin intracellular delivery

Cancer is a leading cause of death. Mesoporous nanomaterials with stimuli sensitivity have received increasing interest as efficient anti-cancer drug carriers. Here, we report hybrid mesoporous nanoparticles of PEGylated silica-poly[2-(dimethylamino)ethyl acrylate] (PEGylated MSN-g-PDMAEA) that can deliver and release the anti-cancer drug doxorubicin (DOX) to tumor cells in a pH dependent switch on/off status. The reversible pH sensitivity resulted in nanoparticles with enhanced functionality through controllable release of the anticancer drug. Confocal laser scanning microscopy (CLSM) and three dimensional (3D) image capture of the intracellular localization of nanoparticles revealed the fast and efficient drug delivery in the human hepatocellular carcinoma cell line. The results highlight the potential of these pH sensitive silica nanoparticles as a novel system for the delivery and controlled release of hydrophobic anti-cancer drugs in the treatment of solid tumors.