Wenting Zheng

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 = vitamin C). 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.

Surface-Induced Hydrogelation Inhibits Platelet Aggregation

We demonstrate that a tripeptide hydrogelator, Nap-FFG, can selectively self-assemble at the surface of platelets, thus inhibiting ADP-, collagen-, thrombin- and arachidonic acid (AA)-induced human platelet aggregations with the IC(50) values of 0.035 (41), 0.14 (162), 0.062 (68), and 0.13 mg/mL (148 μM), respectively. Other tripeptide hydrogelators with chemical structures of Nap-FFX (X = A, K, S, or E) could not or possessed less potencies to inhibit platelet aggregations. We observed higher amounts of Nap-FFG at the platelet surface by the techniques of LC-MS and confocal microscopy. We also observed self-assembled nanofibers around the platelet incubated with the Nap-FFG by cryo-TEM. The ζ potential of Nap-FFG treated platelets was a little bit more negative than that of untreated ones. The amount of Nap-FFG at the surface of NIH 3T3 cells was much less than that of platelets. These observations suggested that Nap-FFG could selectively self-assemble through unknown ligand-receptor interactions and form thin layers of hydrogels at the surface of platelets, thus preventing the aggregation of them. This study not only broadened the application and opened up a new door for biomedical applications of molecular hydrogels but also might provide a novel strategy to counteract infection diseases through selective surface-induced hydrogelations at pathogens, such as bacteria and virus.

Fabrication of highly interconnected porous silk fibroin scaffolds for potential use as vascular grafts

Silk fibroin (SF) scaffolds have been designed and fabricated for multiple organ engineering owing to SFs remarkable mechanical property, excellent biocompatibility and biodegradability, as well as its low immunogenicity. In this study, an easy-to-adopt and mild approach based on a modified freeze-drying method was developed to fabricate a highly interconnected porous SF scaffold. The physical properties of the SF scaffold, including pore morphology, pore size, porosity and compressive modulus, could be adjusted by the amount of ethanol added, the freezing temperature and the concentration of SF. Fourier transform infrared spectroscopy illustrated that treatment of the lyophilized scaffolds with 90% methanol led to a structure transition of SF from silk I (random coil) to silk II (beta-sheet), which stabilized the SF scaffolds in water. We also incorporated heparin during fabrication to obtain a heparin-loaded scaffold which possessed excellent anticoagulant property. The heparin that was incorporated into the SF scaffolds could be released in a sustain manner for approximately 7days, inhibiting the proliferation of human smooth muscle cells within the scaffold in vitro while promoting neovascularization in vivo. We therefore propose that the SF porous scaffold fabricated here may be an attractive candidate for use as a potential vascular graft for implantation based on its high porosity, excellent blood compatibility and mild fabrication process.

Functionalization of the surface of electrospun poly(epsilon-caprolactone) mats using zwitterionic poly(carboxybetaine methacrylate) and cell-specific peptide for endothelial progenitor cells capture

A novel approach for vascular grafts to achieve rapid endothelialization is to attract endothelial progenitor cells (EPCs) from peripheral blood onto grafts via EPC-specific antibodies, aptamer, or peptides that specifically bind to EPCs. Inspired by this idea, the electrospun poly(epsilon-caprolactone) (PCL) mats were modified with zwitterionic poly(carboxybetaine methacrylate) (PCBMA) and phage display-selected-EPC-specific peptide, TPSLEQRTVYAK (TPS). We tested the physical and chemical properties, cyto-compatibility, and platelet adhesion of the modified material, and investigated the specificity of the functionalized surface for capturing EPCs. The results indicated that PCL modified with zwitterionic PCBMA and TPS peptide showed improved hydrophilicity without morphology change and damage of the mats. Furthermore, the modified material supported adherence and growth of vascular cells and resisted platelets adhesion. The surfaces also specifically captured EPCs rather than bone marrow mesenchymal stem cells and human umbilical vein endothelial cells. This surface-functionalized PCL graft may offer new opportunities for designing new vascular grafts.

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.

Three-Layered PCL Grafts Promoted Vascular Regeneration in a Rabbit Carotid Artery Model.

In this study, a three layered poly (ε-caprolactone) (PCL) graft (tPCL) was fabricated by electrospinning PCL and electrospraying poly (ethylene oxide) (PEO), which has a thin dense inner layer, a loose middle layer, and a dense outer layer. Regular PCL grafts (rPCL) with only a dense layer were used as control. In vivo evaluation was performed in rabbit carotid artery. Enhanced cell infiltration, rapid regeneration of endothelium and smooth muscle layers, and increased elastin deposition were observed within the tPCL graft wall. After 3 months, tPCL grafts showed faster PCL degradation than the rPCL grafts. Infiltrated macrophages in the tPCL grafts secreted higher level of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) which enhanced vascular regeneration. In conclusion, the tPCL graft may be a useful vascular prosthesis and worth for further investigation.