Deling Kong

Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model

To address the growing demand of small-diameter vascular grafts for cardiovascular disease, it is necessary to develop substitutes with bio-functionalities, such as anticoagulation, rapid endothelialization, and smooth muscle regeneration. In this study, the small-diameter tubular grafts (2.2 mm) were fabricated by electrospinning of biodegradable polymer polycaprolactone (PCL) followed by functional surface coating with an arginine-glycine-aspartic acid (RGD)-containing molecule. The healing characteristics of the grafts were evaluated by implanting them in rabbit carotid arteries for 2 and 4 weeks. Results showed that at both time points, all 10 of the RGD-modified PCL grafts (PCL-RGD) were patent, whereas 4 of the 10 non-modified PCL grafts were occluded due to thrombus formation. Scanning electron microscopy (SEM) data showed abundant platelets adhering on the surface of the midportion of the PCL grafts. In contrast, only few platelets were observed on the PCL-RGD surface, suggesting that RGD modification significantly improved the hemocompatibility of the PCL grafts. Histological analysis demonstrated enhanced cell infiltration and homogeneous distribution within the PCL-RGD grafts in comparison with the PCL grafts. Furthermore, immunofluorescence staining also showed a 3-fold increase of endothelial coverage of the PCL-RGD grafts than that of PCL grafts at those two time points. After 4-week implantation, 65.3 ± 7.6% of the surface area of the PCL-RGD grafts was covered by smooth muscle cell layer, which is almost 23% more than that on the PCL grafts. The present study indicates that RGD-modified PCL grafts exhibit an improved remodeling and integration capability in revascularization.

Switchable Catalytic Activity: Selenium‐Containing Peptides with Redox‐Controllable Self‐Assembly Properties

Mimicking nature: The reversible formation of self-assembled nanostructures of selenium-containing peptides can be controlled by redox triggers (see scheme, VC = vitaminu2005C). As a consequence, the catalytic activity of these peptides is switchable. These results should lead to the development of nature-mimicking smart materials with promising properties.

A structure–gelation ability study in a short peptide-based ‘Super Hydrogelator’ system

The development of small molecules that can efficiently gel water is of great interest for researchers in the field of self-assembly. We recently found that a short peptide-based molecule (Nap-GFFpY-OMe) could form hydrogels at a minimum gelation concentration of 0.01 wt% after enzymatic conversion, which was the most efficient small molecular hydrogelator reported up to now. In order to study the relationship between the chemical structure and the gelation ability for these short peptide-based gelators, we designed and synthesized a small library of compounds with similar chemical structures to Nap-GFFpY-OMe. They have different capping groups for the amine on glycine (G), different numbers of glycines, different numbers of phenylalanines (F), and different groups at the C-terminus of the peptides. Based on the results, we concluded that the compounds were ‘super gelators’ when their amine capping group was naphthalene, the number of G residues was odd (one and three), the number of F residues was two, and the C-terminus of the peptide was a methyl ester. We found that 10 compounds within the library could form hydrogels and the hydrogels were characterized by rheology, transmission electron microscopy (TEM), and fluorescence spectroscopy. The cytotoxicity of all the precursors of the gelators were also evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and we found that three precursors possessed obviously bigger IC50 values than their corresponding minimum gelation concentrations (MGCs). This study not only suggests the potential applications of our gel system in biomedical fields, but also provides useful information for the molecular design of short peptide-based hydrogelators with excellent gelation abilities.

pH/Sugar Dual Responsive Core-Cross-Linked PIC Micelles for Enhanced Intracellular Protein Delivery

Herein, a series of biocompatible, robust, pH/sugar-sensitive, core-cross-linked, polyion complex (PIC) micelles based on phenylboronic acid-catechol interaction were developed for protein intracellular delivery. The rationally designed poly(ethylene glycol)-b-poly(glutamic acid-co-glutamicamidophenylboronic acid) (PEG-b-P(Glu-co-GluPBA)) and poly(ethylene glycol)-b-poly(l-lysine-co-ε-3,4-dihydroxyphenylcarboxyl-L-lysine) (PEG-b-P(Lys-co-LysCA)) copolymers were successfully synthesized and self-assembled under neutral aqueous condition to form uniform micelles. These micelles possessed a distinct core-cross-linked core-shell structure comprised of the PEG outer shell and the PGlu/PLys polyion complex core bearing boronate ester cross-linking bonds. The cross-linked micelles displayed superior physiological stabilities compared with their non-cross-linked counterparts while swelling and disassembling in the presence of excess fructose or at endosomal pH. Notably, either negatively or positively charged proteins can be encapsulated into the micelles efficiently under mild conditions. The in vitro release studies showed that the release of protein cargoes under physiological conditions was minimized, while a burst release occurred in response to excess fructose or endosomal pH. The cytotoxicity of micelles was determined by cck-8 assay in HepG2 cells. The cytochrome C loaded micelles could efficiently delivery proteins into HepG2 cells and exhibited enhanced apoptosis ability. Hence, this type of core-cross-linked PIC micelles has opened a new avenue to intracellular protein delivery.

A Multifunctional Nanocarrier Based on Nanogated Mesoporous Silica for Enhanced Tumor-Specific Uptake and Intracellular Delivery

A multifunctional drug delivery system based on MCM-41-type mesoporous silica nanoparticles is described that behaves as if nanogates were covalently attached to the outlets of the mesopores through a highly acid-sensitive benzoic-imine linker. Tumor-specific uptake and intracellular delivery results from the pH-dependent progressive hydrolysis of the benzoic-imine linkage that starts at tumor extracellular pH = 6.8 and increases with decreasing pH. The cleavage of the benzoic-imine bond leads to the removal of the polypseudorotaxane caps and subsequent release of the payload drugs at tumor sites. At the same time, the carrier surface becomes positively charged, which further facilitates cellular uptake of the nanocarriers, thus offering a tremendous potential for targeted tumor therapy.

A hybrid hydrogel for efficient removal of methyl violet from aqueous solutions

In this study, we reported on the incorporation of a novel supramolecular hydrogel into agarose hydrogel to create a hybrid hydrogel. Both the supramolecular hydrogel and the hybrid hydrogel were characterized by scanning electron microscopy (SEM) and fluorescence microscopy, and their mechanical properties were evaluated by a compress assay. These results showed that the hybrid hydrogel possessed much better mechanical properties and stability than the supramolecular hydrogel itself. The hybrid hydrogel could be applied to efficiently remove methyl violet from an aqueous phase without affecting its appearance under vigorous stirring, while the supramolecular hydrogel changed to a fragile solid after the absorption of a large amount of methyl violet even under the free-standing mode. Such a hybrid hydrogel has the potential for use in the efficient removal of dye molecules from aqueous solutions.

Small-diameter tissue engineered vascular graft made of electrospun PCL/lecithin blend

In this study, natural lecithin was incorporated into cholesterol-poly(ε-caprolactone) (Chol-PCL) by solution blending in order to modify the performance of the hydrophobic and bio-inert PCL. The fibrous Chol-PCL/lecithin membranes were fabricated by electrospinning, and the surface morphology and properties were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, static water contact angle, and mechanical tensile testing. The blood compatibility of the scaffolds was evaluated by in vitro hemolysis assay. The cytocompatibility of the scaffolds was investigated by cell adhesion and proliferation using bone-marrow mesenchymal stem cells (MSCs). Subcutaneous implantation was also performed to evaluate the in vivo inflammatory reaction. The tubular tissue-engineered vascular graft (TEVG) was further constructed by rolling cell sheet comprising fibrous membrane and MSCs. Furthermore, endothelial cells (ECs) were seeded onto the lumen of the graft with the aim to form vascular endothelium. The preliminary results indicate that electrospun Chol-PCL/lecithin scaffolds show improved hemocompatibility and cytocompatibility compared with neat Chol-PCL, and combining the Chol-PCL/lecithin fibrous scaffold with MSCs and ECs with well controlled distribution is a promising strategy for constructing TEVGs.

Highly stable surface modifications of poly(3-caprolactone) (PCL) films by molecular self-assembly to promote cells adhesion and proliferation

In this paper, we report a simple and versatile surface coating method to functionalize poly(3-caprolactone) (PCL) films by molecular self-assembly of a hydrogelator.

Phase morphology, physical properties, and biodegradation behavior of novel PLA/PHBHHx blends.

In this study, two biodegradable polyesters [i.e., polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx)] with complementarity in terms of mechanical performance have been combined, and a series of blends with a broad range of compositions has been prepared by thermal compounding. The evolution of phase morphologies with the variation of compositions has been characterized by using Fourier transform infrared spectroscopic imaging together with scanning electron microscope analyses. Thermal, mechanical, and biodegradation properties of the PLA/PHBHHx blends were systematically investigated. Mechanical properties were further analyzed by using theoretical models and correlated with the results of the morphology/structure and compatibility of the blends. Results indicate that PLA/PHBHHx blends are immiscible but can be compatible to some extent at certain compositions (e.g., PLA/PHBHHx (w/w) = 80/20 and 20/80). The physical properties of the blend could be fine tuned by adjusting the blend composition.

A thixotropic molecular hydrogel selectively enhances Flk1 expression in differentiated murine embryonic stem cells

Hydrogels are considered as promising materials for maintenance and directed differentiation of embryonic stem (ES) cells. We designed and synthesized a molecular gelator, which was a collagen mimic related to sequence. The hydrogel was found to be thixotropic and it was characterized by different techniques in detail, including rheometery, TEM, CD, FT-IR, and fluorescence spectrometery. More importantly, we demonstrated that our molecular hydrogel supported the differentiation of murine ES cells, and could selectively enhance Flk1 expression in differentiated mES cells. Flk1-positive cells derived from ES cells had been demonstrated as vascular progenitors that support the formation of vascular system. Thus, our hydrogel had great potentials for the preparation of a pure population of Flk1-positive cells, which could be used for the study of vascular formation. Our study is the first example of using molecular hydrogels for mES cell differentiation, which will promote future application of both molecular hydrogels and stem cells in regenerative medicine.