De-Qun Wu

Fabrication of Supramolecular Hydrogels for Drug Delivery and Stem Cell Encapsulation

Supramolecular hydrogels self-assembled by alpha-cyclodextrin and methoxypolyethylene glycol-poly(caprolactone)-(dodecanedioic acid)-poly(caprolactone)-methoxypolyethylene glycol (MPEG-PCL-MPEG) triblock polymers were prepared and characterized in vitro and in vivo. The sustained release of dextran-fluorescein isothiocyanate (FITC) from the hydrogels lasted for more than 1 month, which indicated that the hydrogels were promising for controlled drug delivery. ECV304 cells and marrow mesenchymal stem cells (MSC) were encapsulated and cultured in the hydrogels, during which the morphologies of the cells could be kept. The in vitro cell viability studies and the in vivo histological studies demonstrated that the hydrogels were non-cytotoxic and biocompatible, which indicated that the hydrogels prepared were promising candidates as injectable scaffolds for tissue engineering applications.

Galactosylated fluorescent labeled micelles as a liver targeting drug carrier

Galactosylated and fluorescein isothiocyanate (FITC) labeled polycaprolactone-g-dextran (Gal-PCL-g-Dex-FITC) polymers were synthesized. The grafted polymers can self-assemble into stable micelles in aqueous medium and in serum. Transmission electron microscopy (TEM) images showed that the self-assembled micelles were regularly spherical in shape. Micelle size determined by size analysis was around 120 nm. The anti-inflammation drug prednisone acetate as a model drug was loaded in the polymeric micelles, and the in vitro drug release was investigated. The galactosylated micelles could be selectively recognized by HepG2 cells and subsequently accumulate in HepG2 cells. The in vivo study demonstrated the relative uptake of the micelles by liver is much higher than the other tissues, indicating that the galactosylated micelles have great potential as a liver targeting drug carrier.

Chitosan based oligoamine polymers: Synthesis, characterization, and gene delivery

A series of chitosan-based oligoamine polymers was synthesized from N-maleated chitosan (NMC) via Michael addition with diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and linear polyethylenimine (M(n) 423), respectively. The resulted polymers exhibited well binding ability to condense plasmid DNA to form complexes with size ranging from 200 to 600 nm when the polymer/DNA weight ratio was above 7. The polymer/DNA complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The cytotoxicity assay showed that the synthesized polymers were less toxic than that of PEI(25 K). The gene transfection effect of resulted polymers was evaluated in 293T and HeLa cells, and the results showed that the gene transfection efficiency of these polymers was better than that of chitosan. Moreover, the transfection efficiency was dependent on the length of the oligoamine side chains and the molecular weight of the chitosan derivatives.

Bone marrow stem cells implantation with α-cyclodextrin/MPEG–PCL–MPEG hydrogel improves cardiac function after myocardial infarction

Cellular transplantation represents a promising therapy for myocardial infarction (MI). However, it is limited by low transplanted cell retention and survival within the ischemic tissue. This study was designed to investigate whether injectable alpha-cyclodextrin/poly(ethylene glycol)-b-polycaprolactone-(dodecanedioic acid)-polycaprolactone-poly(ethylene glycol) (MPEG-PCL-MPEG) hydrogel could improve cell transplant retention and survival, reduce infarct expansion and inhibit left ventricle (LV) remodeling. Bone marrow-derived stem cells (BMSCs) were encapsulated in alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel and maintained their morphologies during the cell culturing. MTT assays were used for in vitro cell viability studies of the hydrogel and were shown to be non-cytotoxic. Seven days after MI, 100 microl of alpha-cyclodextrin solution containing 2 x 10(7) BMSCs and 100mul of MPEG-PCL-MPEG solution were injected into the infarcted myocardium simultaneously and the solutions solidified immediately. Injection of culture medium or cell alone served as controls. Four weeks after treatment, histological analysis indicated that the hydrogel was absorbed, and the injection of BMSCs with hydrogel had increased cell retention and vessel density around the infarct, and subsequently prevented scar expansion compared with BMSCs injection alone. Echocardiography studies showed that injection of BMSCs with hydrogel increased the LV ejection function and attenuated left ventricular dilatation. This study indicated that the injection of BMSCs with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel was an effective strategy which could enhance the effect of cellular transplantation therapy for myocardial infarction.

Novel thermosensitive hydrogel injection inhibits post-infarct ventricle remodelling

Myocardial infarction (MI) remains the commonest cause of cardiac‐related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling.

Biodegradable and pH-Sensitive Hydrogels for Cell Encapsulation and Controlled Drug Release

Hydrogels with pH-sensitive poly(acrylic acid) (PAAc) chains and biodegradable acryloyl-poly(-caprolactone)-2-hydroxylethyl methacrylate (AC-PCL-HEMA) chains were designed and synthesized. The morphology of hydrogel was observed by scanning electron microscopy. The degradation of the hydrogel in the presence of Pseudomonas lipase was studied. The in vitro release of bovine serum albumin from the hydrogel was investigated. Cytotoxicity study shows that the AC-PCL-HEMA/AAc copolymer exhibits good biocompatibility. Cell adhesion and migration into the hydrogel networks were evaluated by using different cell lines. The hydrogel with a lower cross-linking density and a larger pore size exhibited a better performance for cells migration.

Injection of a novel synthetic hydrogel preserves left ventricle function after myocardial infarction

Myocardial infarction (MI) and the subsequent heart failure remain one of the leading causes of morbidity and mortality world wide. A number of studies have demonstrated that bioderived materials improve cardiac function after implantation because of their angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricular (LV) function through its prevention of paradoxical systolic bulging. To test this hypothesis, infarction was induced in rabbit myocardium by coronary artery ligation. After 1 week, 200-microL alpha-cyclodextrin (alpha-CD)/MPEG-PCL-MPEG hydrogel was injected into the infarcted myocardium. Injection of phosphate buffered saline (PBS) served as controls. Twenty-eight days after the treatment, histological analysis indicated that the injection of hydrogel prevented scar expansion and wall thinning compared with the control (p < 0.05) without more microvessel density in infarcted myocardium (p = 0.70). LV ejection fraction, determined by echocardiography, was significantly greater in the hydrogel-treated group (56.09% +/- 8.42%) than the control group (37.26% +/- 6.36%, p = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 +/- 0.33 cm and 1.74 +/- 0.30 cm, respectively, in the control group. Smaller LV end-diastolic diameter (1.61 +/- 0.26 cm, p = 0.005) and smaller end-systolic diameter (1.17 +/- 0.23 cm, p = 0.001) were found in the hydrogel-treated group. These results suggest that alpha-CD/MPEG-PCL-MPEG hydrogel could serve as an injectable biomaterial that prevents LV remodeling and dilation for the treatment of MI.

Toward the Development of Partially Biodegradable and Injectable Thermoresponsive Hydrogels for Potential Biomedical Applications

A series of hydrogels containing a biodegradable dextran (Dex) chain grafted with a hydrophobic poly(-caprolactone)-2-hydroxylethyl methacrylate (PCL-HEMA) chain and a thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) chain were synthesized. The molecular weight of PCL-HEMA was determined by gel permeation chromatography, and the inner morphology of the hydrogel was observed by scanning electron microscopy. The release profiles from the hydrogels were investigated using bovine serum albumen as a model drug. It was found that the release behavior could be adjusted by varying the composition of the hydrogel. In vitro cytotoxicity studies of the hydrogels showed that the copolymer Dex-PCL-HEMA/PNIPAAm exhibited low cytotoxicity. The in vivo degradation and histological studies demonstrated that the hydrogels had good biocompatibility and were promising for use as an injectable polymeric scaffold for tissue engineering applications.

Porphyrin and Galactosyl Conjugated Micelles for Targeting Photodynamic Therapy

PurposeTo study the targeting and photodynamic therapy efficiency of porphyrin and galactosyl conjugated micelles based on amphiphilic copolymer galactosyl and mono-aminoporphyrin (APP) incoporated poly(2-aminoethyl methacrylate)-polycaprolactone (Gal-APP-PAEMA-PCL).MethodsPoly(2-aminoethyl methacrylate)-polycaprolactone (PAEMA-PCL) was synthesized by the combination of ring opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization, and then Gal-APP-PAEMA-PCL was obtained after conjugation of lactobionic acid and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (APP) to PAEMA-PCL. The chemical structures of the copolymers were characterized, and their biological properties were evaluated in human laryngeal carcinoma (HEp2) and human hepatocellular liver carcinoma (HepG2) cells.ResultsBoth APP-PAEMA-PCL and Gal-APP-PAEMA-PCL did not exhibit dark cytotoxicity to HEp2 cells and HepG2 cells. However, Gal-APP-PAEMA-PCL was taken up selectively by HepG2 cells and had the higher phototoxicity effect. Both polymers preferentially localized within cellular vesicles that correlated to the lysosomes.ConclusionsThe results indicated that porphyrin and galactosyl conjugated polymer micelles exhibited higher targeting and photodynamic therapy efficacy in HepG2 cells than in HEp2 cells.

Injectable Hydrogel Helps Bone Marrow-Derived Mononuclear Cells Restore Infarcted Myocardium

Backgrounds: Experimental and clinical studies have suggested that cell implantation could improve cardiac function after myocardial infarction (MI). However, this technique was limited by decreased engraftment and survival of transplanted cells within the ischemic tissue. The present study was performed to investigate whether implantation of bone marrow-derived mononuclear cells (BMMNCs) encapsulated in hydrogel could increase cell engraftment and help to restore cardiac function of MI rabbits. Methods: MI was induced in rabbits by coronary artery ligation. One week later, cell culture medium, Dex-PCL-HEMA/PNIPAAm hydrogel, BMMNCs in medium or BMMNCs in hydrogel were injected into the infarcted area of the left ventricle (LV). Results: Increased cell engraftment was observed 48 h after injection when cells were encapsulated in hydrogel; 30 days after treatment, echocardiographic studies showed that injection of BMMNCs in hydrogel preserved LV ejection fraction and attenuated LV dilatation compared with other groups. Histological analysis indicated that injection of BMMNCs in hydrogel enhanced neovascular formation and prevented scar expansion compared with the other groups. Conclusion: Injection of hydrogel-encapsulated BMMNCs increased cell engraftment and improved LV function; this technique may serve as an effective approach to restore infarcted myocardium.