Sheng Meng

The effect of a layer-by-layer chitosan-heparin coating on the endothelialization and coagulation properties of a coronary stent system

A biomacromolecular layer-by-layer coating process of chitosan/heparin onto a coronary stent is designed for the acceleration of the re-endothelialization and healing process after coronary stent deployment. The results of in vitro culturing of porcine iliac artery endothelial cells as well as the measurements of the APTT, PT and TT supported the rationale that the combination of chitosan and heparin could bring both endothelial cell compatibility and haemocompatibility to the stent surface. A porcine coronary injury model and arteriovenous shunt model were used for the further evaluation of the application of this kind of surface-modified stainless steel stent in vivo. The final results proved that this facile coating approach could significantly promote re-endothelialization and was safer compared with bare metal stents for its much improved anticoagulation property.

Synthesis of a zwitterionic silane and its application in the surface modification of silicon-based material surfaces for improved hemocompatibility.

A phosphorylcholine-like silane coupling agent bearing zwitterionic molecular structure was synthesized and studied. The chemical structure of this silane coupling agent was characterized by FTIR, 1H NMR and 31P NMR. The zwitterionic structure was successfully constructed onto the surface of silicon as a self-assembled layer (SAL). Static water contact angle, and atomic force microscopy (AFM) were used to investigate the wettability and surface topography of the modified silicon surfaces. Static water contact angle results indicated that the hydrophilicity of the surfaces could be effectively improved by the modification with this zwitterionic silane coupling agent. The changes of the topography and water contact angle of the modified surfaces with different incubation periods in PBS solution were also measured to evaluate the stability of the SALs. Blood compatibility of the modified surfaces were evaluated by testing the full-blood activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT), as well as by observing the adhered blood platelets onto the surface. The modified surfaces showed prolonged clotting time and fewer adherent platelets, revealing that the blood compatibility was evidently improved by the modification using this zwitterionic silane.

Novel drug-loaded gelatin films and their sustained-release performance.

A new particulate drug delivery system with gelatin matrix containing Ibuprofen as a model drug molecule was developed for an epidermis drug prolonged release. Gelatin films containing Ibuprofen-loaded poly-epsilon-caprolactone (PCL) microspheres have been developed on evaporation of organic solvent from an oil-in-water emulsion followed by cross-linking. The microspheres were characterized for particle size, encapsulation efficiency, and surface morphology. Water uptake, matrix erosion, and drug release profile of the microsphere-film system were investigated. The results indicated that drug-loaded microspheres introduced in this system successfully prolonged drug release time. This kind of microsphere-film system combined good adhesion, typical for gelatin films, with the sustained release performance of PCL microspheres.

Studies on a Novel Multi-sensitive Hydrogel: Influence of the Biomimetic Phosphorylcholine End-Groups on the PEO–PPO–PEO Tri-block Co-polymers

In the present study, a biomimetic phosphorylcholine group was employed in the end-capping modification of PEO–PPO–PEO tri-block co-polymers (Pluronic®). The structures of the resulting materials were characterized by 1H-NMR and GPC. The effects of the additional phosphorylcholine end-groups to the thermo-sensitive sol–gel transition behaviors of the aqueous solutions of the resulting polymers were studied by rheology test in neutral (0.1 M NaCl) aqueous solutions and in acidic solutions (pH 3). It was found that the phosphorylcholine-end-capped Pluronic hydrogels still kept their thermo-sensitive mechanical properties with a slight change on the sol–gel transition behaviors. The phosphorylcholine-modified Pluronics exhibited a response to the change of the pH value, which made this kind of material a multi-sensitive hydrogel system. Also, the resulting polymers showed improved hemocompatibilities in the blood coagulation test using full human blood.

Novel biodegradable blend matrices for controlled drug release.

Phosphorylcholine-functionalized poly-epsilon-caprolactone (PC-PCL) is a new biodegradable polymer with good biocompatibility. In this study modulation of the controlled release of Ibuprofen (IB), a model drug, from poly-epsilon-caprolactone (PCL) by direct blending with PC-PCL is investigated. The influence of several factors such as the content of PC-PCL in the blend, drug loading and the molecular weight of PCL matrix upon the IB release is recognized. The release mechanism is discussed in terms of degradation/erosion profiles and hydrophilicity of the blend matrices. The IB release rate increased with the PC-PCL content because PC-PCL increased the hydrophilicity and biodegradability of the blends. Simultaneously, that release rate decreased with increase in the molecular weight of PCL in the blend. The drug loading in the blend also affected the release property of the matrix. Analysis of the release profiles following the power law indicated that the IB release was governed mainly by diffusion kinetics.

Immobilization of biomacromolecules on poly-L-lactide surface via a layer-by-layer method for the improving of its cytocompatibility to bone marrow stromal cells

Hyaluronic acid (HA) and chitosan (CS) were immobilized on the surface of poly-L-lactide (PLLA) by the following procedure: Firstly, PLLA was aminolyzed with 1, 6-hexanediamine, and part of the PLLA surface ester groups were converted to free amino groups. Then negatively charged hyaluronic acid and positively charged chitosan were deposited onto the surface of aminolyzed PLLA film in a layer-by-layer assembly manner. The effect of the layer-by-layer deposition was evaluated by ATR-FTIR spectroscopy, Raman spectroscopy and static contact angle measurements. The cytocompatibility of PLLA sample to bone marrow stromal cells (BMSCs) was improved after modification with chitosan and HA. The cell attachment, activity, and proliferation on CS/HA modified PLLA films were enhanced comparing with the control. The cells cultured on the modified PLLA samples excreted abundant cytoplasm and can differentiate to vascular smooth muscle (SM)-like (SM-like) cells. A macroporous three-dimensional PLLA scaffold was prepared by integrating both the technique of freeze-drying and particle leaching. Layer-by-layer modification by HA/CS and cell culture was also applied on this scaffold. The scaffold cultured with BMSCs for 2 weeks has been tested successfully in vivo as a patch for repairing the artificial incision on canine pulmonary artery.

Improving the biocompatibility of poly(ε-caprolactone) by surface Immobilization of chitosan and heparin

Abstract Oppositely charged natural polyelectrolyte Heparin (HS) and chitosan (CS) were immobilized on the surface of poly(ε-caprolactone) (PCL) by a layer-bylayer (LBL) self-assembly procedure. Positively charged poly(allylamine hydrochloride) (PAH) was used as the first layer onto the surface of PCL. Then negatively charged HS and positively charged CS were deposited in a LBL assembly manner. The effect of this surface modification method was evaluated by ATR-FTIR spectroscopy and static contact angle measurements. The anticoagulant activity of modified PCL was evaluated using full human blood. The modified PCL samples showed prolonged activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboplastin time (TT) compared with neat PCL. Scanning electron microscopy (SEM) indicated that adhered platelets retained their natural, round morphology on the modified PCL surface. The cytocompatibility of the HS/CS surface modified PCL sample was evaluated with pig iliac arteries endothelial cells (PIECs). The proliferation of the cells cultured on modified PCL films was better than those on neat PCL films.