Changyou Gao

A complementary density gradient of zwitterionic polymer brushes and NCAM peptides for selectively controlling directional migration of Schwann cells.

Selective enhancement of directional migration of Schwann cells (SCs) over fibroblasts (FIBs) plays a significant role in peripheral nerve regeneration, because this behavior facilitates neuron repair and avoids fibrosis. Herein a complementary density gradient of poly(3-dimethyl-methacryloyloxyethyl ammonium propane sulfonate) (PDMAPS, a zwitterionic polymer with antifouling property) and KHIFSDDSSE peptide (KHI, derived from neural cell adhesion molecule NCAM which mediates cell-cell adhesion) was fabricated. The gradient was visualized by fluorescent labeling, and further characterized by X-ray photoelectron spectrometry (XPS) and quartz crystal microbalance with dissipation (QCM-d). The SCs exhibited preferential orientation and enhanced directional migration on the gradient surface toward the region of lower PDMAPS density and higher KHI peptide density, while FIBs showed random migration. Moreover, the migration rate of the SCs was significantly enhanced to 2 folds, whereas that of the FIBs was reduced to 60% compared to their natural state on glass, leading to a faster migration rate of SCs than FIBs. The success of the complementary gradient relies on the appropriate interplay between the PDMAPS brushes and the cell-specific ligands, enabling the selective guidance of SCs migration.

Combinational effect of matrix elasticity and alendronate density on differentiation of rat mesenchymal stem cells

Differentiation of mesenchymal stem cells (MSCs) is regulated by multivariate physical and chemical signals in a complicated microenvironment. In this study, polymerizable double bonds (GelMA) and osteo-inductive alendronate (Aln) (Aln-GelMA) were sequentially grafted onto gelatin molecules. The biocompatible hydrogels with defined stiffness in the range of 4-40 kPa were prepared by using polyethylene glycol diacrylate (PEGDA) as additional crosslinker. The Aln density was adjusted from 0 to 4 μM by controlling the ratio between the GelMA and Aln-GelMA. The combinational effects of stiffness and Aln density on osteogenic differentiation of MSCs were then studied in terms of ALP activity, collagen type I and osteocalcin expression, and calcium deposition. The results indicated that the stiffness and Aln density could synergistically improve the expression of all these osteogenesis markers. Their osteo-inductive effects are comparable to some extent, and high Aln density could be more effective than the stiffness.

Influence of bovine serum albumin coated poly(lactic-co-glycolic acid) particles on differentiation of mesenchymal stem cells

Interaction with colloidal particles may change the structure and function of the cytoskeleton, and influence cell shape and signal pathways, and thereby modulate the differentiation of stem cells. In this study, bovine serum albumin-coated poly(lactic-co-glycolic acid) particles (PLGA–BSA) were prepared and incubated with rat mesenchymal stem cells (MSCs). It was found that they promote osteogenic ALP activity and the expression of collagen type I (COL) and osteocalcin (OCN) of MSCs, but inhibit the expression of adipogenic peroxisome proliferator-activated receptor-gamma (PPARγ) and lipoprotein lipase (LPL) at both mRNA and protein levels. The p38 pathway is altered in the presence of PLGA–BSA particles, which might be responsible for the particle-induced differentiation of MSCs.

Shape Transformation of Light-Responsive Pyrene-Containing Micelles and Their Influence on Cytoviability.

The amphiphilic pyrene-containing random copolymers with light-responsive pyrene ester bonds were synthesized by copolymerizing 1-pyrenemethyl acrylate (PA) and N,N-dimethylacrylamide (DMA). The P(DMA-co-PA) copolymers formed spherical micelles in water, which were transformed into nanorods as a result of cleavage of the pyrene ester bonds under UV irradiation. In vitro culture with A549 cells and Raw cells showed that compared to the nonphotodegradable ones, the photodegradable P(DMA-co-PA) micelles caused significantly higher cytotoxicity under the same UV irradiation. The intracellular reactive oxygen species (ROS) level had a positive correlation with the cytotoxicity regardless of the cell types. The nonphotodegradable pyrene-containing micelles produced a lower level of ROS under UV irradiation. However, the photodecomposable P(DMA-co-PA) micelles produced a significant higher level of ROS under the same trigger of UV irradiation, which caused the shape transformation of micelles to nanorods and higher cytotoxicity simultaneously.

The correlation between fibronectin adsorption and attachment of vascular cells on heparinized polycaprolactone membrane.

The heparin-immobilized polycaprolactone (PCL) membrane was developed to investigate the effect of heparin on the adsorption behaviors of serum proteins, in particular fibronectin (Fn), and the attachment of different types of vascular cells. The heparin was covalently immobilized onto aminolyzed PCL membrane by amidation reaction. The grafting amount of heparin increased from 0.35 μg/cm(2) to 1.31 μg/cm(2) when the aminolysis time was prolonged from 10 min to 60 min. The adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) on the heparinized PCL surface was significantly enhanced and reduced, respectively. The adsorption of Fn was strongly improved on the heparinized PCL surface than on the pristine PCL, and showed a positive correlation with the heparin density. Therefore, the adsorbed Fn takes a decisive role on the selective adhesion of ECs and the suppression of SMCs attachment.

Preparation of gelatin density gradient on poly(e-caprolactone) membrane and its influence on adhesion and migration of endothelial cells

Directional migration of endothelial cells (ECs) can be achieved by gradient cues in vitro, which mimics the corresponding biological events in vivo. Currently, most of the gradients have been prepared on model surfaces which are too simple compared to real degradable biomaterials. In this study, the amino group density gradient was prepared on poly(ε-caprolactone) (PCL) membrane surface by a gradient aminolysis method, which was transferred into gelatin density gradient by covalent linking with glutaraldehyde. The resulted gelatin density gradient ranged from 0.49 to 1.57μg/cm(2) on the PCL membrane. The adhesion, orientation and migration of ECs on the PCL membrane with the gelatin density gradient were studied. The ECs showed preferred orientation and directional migration toward the gradient direction with enhanced gelatin density at proper position (gelatin density), forwarding a new step toward the preparation of applicable gradient biomaterials in tissue regeneration.

Preparation of Novel Porphyrin Nanomaterials Based on the pH-Responsive Shape Evolution of Porphyrin Microspheres

The shapes and properties of self-assembled materials can be adjusted easily using environmental stimuli. Yet, the stimulus-triggered shape evolution of organic microspheres in aqueous solution has rarely been reported so far. Here, a novel type of poly(allylamine hydrochloride)-g-porphyrin microspheres (PAH-g-Por MPs) was prepared by a Schiff base reaction between 2-formyl-5,10,15,20-tetraphenylporphyrin (Por-CHO) and PAH doped in 3.5-μm CaCO3 microparticles, followed by template removal. The PAH-g-Por MPs had an average diameter of 2.5 μm and could be transformed into one-dimensional nanorods (NRs) and wormlike nanostructures (WSs) after being incubated for different times in pH 1-4 HCl solutions. The rate and degree of hydrolysis had a significant effect on the formation and morphologies of the nanorods. The NRs@pH1, NRs@pH2, and NRs@pH3 were all composed of the released Por-CHO and the unhydrolyzed PAH-g-Por because of the incomplete hydrolysis of the Schiff base. However, the WSs@pH4 were formed by a pure physical shape transformation, because they had the same composition as the PAH-g-Por MPs and the Schiff base bonds were not hydrolyzed. The self-assembled NRs and WSs exhibited good colloidal stability and could emit stable red fluorescence over a relatively long period of time.

Protein adsorption and cellular uptake of AuNPs capped with alkyl acids of different length

The chain length of ligands plays an important role in many biomedical applications. Yet the interaction of nanoparticles with surface-capped ligands of different length (especial the hydrophobic chains) and cells is neglected, and thereby the underlying mechanism influencing cellular uptake is unclear. Herein the role of alkyl length on AuNPs in mediating serum protein adsorption and the subsequent cellular uptake by A549 cells was studied. The AuNPs were modified with carboxylic alkyl thiols of different chain length (3MA, 11MA and 16MA), resulting in MA-AuNPs with a size of 5 nm in dry state and several tens of nm in media. The MA-AuNPs possessed a negatively charged surface, whose zeta potential was around −20 mV in serum-containing medium regardless of the length of ligands. Whereas the total amount of adsorbed serum proteins had no significant difference, the relative amounts of adhesion mediators especially vitronectin (Vn) depended on the alkyl length significantly. The 16MA-AuNPs adsorbed the largest amount of Vn, and were internalized by A549 cells with the largest quantity and good distribution in cytoplasm. Taking account all the results, the protein adsorption and its role in linking alkyl length on AuNPs to cellular uptake are figured out.

Preparation of elastic polyurethane microcapsules using CaCO3 microparticles as templates for hydrophobic substances loading

Elastic polyurethane (PU) microcapsules were successfully fabricated via a simple and well controllable adsorption and crosslinking method on porous CaCO3 templates in organic solvent. The PU capsules possessed some amine groups, enabling well dispersion in water. These PU capsules with hydrophobic interiors could load hydrophobic substances such as drugs and dyes from organic solution spontaneously. And the loaded dyes can be well preserved. Their deformation and recovery behaviours were investigated after being forced to flow through a microchannel. Due to their good elasticity, more than 82% squeezed PU capsules could recover their original spherical shape even at a high deformation ratio of 32%. These elastic PU microcapsules with strong shape recovery ability may find diverse applications as microcontainer or microsensor which could survive through harsh conditions like forced deformation.

A primary study of poly(propylene fumarate)–2-hydroxyethyl methacrylate copolymer scaffolds for tarsal plate repair and reconstruction in rabbit eyelids

Eyelid reconstruction includes anterior lamella reconstruction and posterior lamella reconstruction. As an important skeletal component of the posterior lamella, tarsal plates repair is the key issue for eyelid reconstruction. Presently, neither traditional surgery nor autograft/allograft has achieved satisfactory repair effects. Poly(propylene fumarate)-co-2-hydroxyethyl methacrylate (PPF-HEMA) networks with mass ratios of 1u2009:u20090.5, 1u2009:u20091 and 1u2009:u20092 were synthesized and used as the tarsal substitute in this study. Their chemical compositions, swelling ability, and mechanical properties were characterized. Porous scaffolds were fabricated by a gelatin particle leaching method. The in vitro studies of cytotoxicity on human dermal fibroblasts (HDFs) and degradation demonstrated that PPF-HEMA scaffolds did not have noticeable cell cytotoxicity and their degradation rates correlated with the ratio of PPF to HEMA. The PPF-HEMA networks, with mass ratios of 1u2009:u20091 and 1u2009:u20092, and an ADM control were implanted in rabbits with tarsal plate defects for in vivo biocompatibility and degradation behavior evaluation. PPF-HEMA scaffolds provided satisfactory repair results with mild tissue response and biocompatibility to fibroblast growth and fibrous capsulation compared to the ADM control. The tissue compatible and biodegradable PPF-HEMA networks with elastic mechanical properties were proven to be a suitable candidate for tarsal repair.