Heparin mimics and fibroblast growth factor-2 fabricated nanogold composite in promoting neural differentiation of mouse embryonic stem cells.

The replacement therapy or transplantation using neural cells, which differentiated from stem cells, has emerged as a promising strategy for repairing damaged neural tissues and helping functional recovery in the treatment of neural system diseases. The challenge, however, is how to control embryonic stem cell fate so that neural differentiation can be efficiently directed to enrich a neuron cell population, and meanwhile to maintain their bioactivities. This is a key question and has a very significant impact in regenerative medicine. Here we proposed a new neural-differentiation inductive nanocomposite, containing gold nanoparticles (AuNPs), poly(2-methacrylamido glucopyranose-co-3-sulfopropyl acrylate) (PMS), and basic fibroblast growth factor (FGF2), for the high efficient directional neural-specific differentiation of mouse embryonic stem cells (mESCs). In this AuNP-PMS/FGF2 composite, PMS, playing as the high-active mimic of heparin/heparan sulfate (HS), is covalently anchored to AuNPs and bound with FGF2 on the surface of nanoparticles, forming a HS/FGF2 complex nanomimics to facilitate its binding to FGF receptor (FGFR) and promote high neural-inductive activity of mESCs. The stability, bioactivity and biocompatibility of the composite are investigated in this study. The results showed that the AuNP-PMS/FGF2 composite could maintain a long-term stability at room temperature for at least 8 days, and greatly promote the neural differentiation of mESCs. Compared with the other materials, the AuNP-PMS/FGF2 composite could significantly stimulate the expression of the specific neural differentiation markers (nestin and ß3-tubulin), while obviously down-regulate the mRNA production of pluripotency marker Oct-4 in mESCs. Moreover, the promotion effect of the composite on neuronal maturation marker ß3-tubulin expression achieved maximally at the low concentration of FGF2 (4 ng/mL), which suggested the high efficiency of AuNP-PMS/FGF2 composite in neural differentiation of mESCs. Meanwhile, both mESCs and L929 cells showed desirable growth during the incubation with AuNP-PMS/FGF2 composite. The AuNP-PMS/FGF2 system presents a new way to achieve HS/FGF2 complex nanomimics efficiently for the neural differentiation of mESCs.

Universal Antibacterial Surfaces Fabricated from Quaternary Ammonium Salt-Based PNIPAM Microgels.

Because of the excellent film-forming ability of poly(N-isopropylacrylamide) (PNIPAM) microgel and high-efficient bactericidal property of quaternary ammonium salt (QAS), QAS-based PNIPAM (QAS-PNIPAM) microgels are synthesized and employed to modify the surface of a range of commonly used materials including metal, plastic, and elastomer. Bacterial culture is carried out on such QAS-PNIPAM microgel-modified surfaces to examine the viability of the attached bacteria. It is found that the bactericidal efficiency is nearly 100% on the modified surfaces of all the studied materials. We attribute the high-efficient bactericidal performance of QAS-PNIPAM microgel film to the QAS component rather than the topography of the microgel film itself. In addition, the microgel film is robust and shows great integrity even after culture of the bacteria and repeated rinses, and the cell experiment demonstrates that this microgel film is cyto-compatible. Therefore, such a simple, versatile method of preparing antibacterial films paves the way for future bactericidal applications.

Deciphering the Role of Sulfonated Unit in Heparin-Mimicking Polymer to Promote Neural Differentiation of Embryonic Stem Cells.

Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), hold great potential for inducing the neural differentiation of embryonic stem cells (ESCs) and have brought new hope for the treatment of neurological diseases. However, the disadvantages of natural heparin/HS, such as difficulty in isolating them with a sufficient amount, highly heterogeneous structure, and the risk of immune responses, have limited their further therapeutic applications. Thus, there is a great demand for stable, controllable, and well-defined synthetic alternatives of heparin/HS with more effective biological functions. In this study, based upon a previously proposed unit-recombination strategy, several heparin-mimicking polymers were synthesized by integrating glucosamine-like 2-methacrylamido glucopyranose monomers (MAG) with three sulfonated units in different structural forms, and their effects on cell proliferation, the pluripotency, and the differentiation of ESCs were carefully studied. The results showed that all the copolymers had good cytocompatibility and displayed much better bioactivity in promoting the neural differentiation of ESCs as compared to natural heparin; copolymers with different sulfonated units exhibited different levels of promoting ability; among them, copolymer with 3-sulfopropyl acrylate (SPA) as a sulfonated unit was the most potent in promoting the neural differentiation of ESCs; the promoting effect is dependent on the molecular weight and concentration of P(MAG-co-SPA), with the highest levels occurring at the intermediate molecular weight and concentration. These results clearly demonstrated that the sulfonated unit in the copolymers played an important role in determining the promoting effect on ESCs' neural differentiation; SPA was identified as the most potent sulfonated unit for copolymer with the strongest promoting ability. The possible reason for sulfonated unit structure as a vital factor influencing the ability of the copolymers may be attributed to the difference in electrostatic and steric hindrance effect. The synthetic heparin-mimicking polymers obtained here can offer an effective alternative to heparin/HS and have great therapeutic potential for nervous system diseases.

Promoting neural differentiation of embryonic stem cells using ß-cyclodextrin sulfonate.

A heparin-mimicking biomolecule, ß-cyclodextrin decorated with sulfonate groups (CD-S), was synthesized. CD-S itself exhibited bioactivity similar to that of heparin and can further serve as a carrier for all-trans retinoic acid by forming inclusion complexes that promote neural differentiation of embryonic stem cells more effectively than heparin.