Jiang Yuan

Grafting of carboxybetaine brush onto cellulose membranes via surface-initiated ARGET-ATRP for improving blood compatibility

Grafting-from has proven to be a very effective way to create high grafting densities and well-controlled polymer chains on different kinds of surfaces. In this work, we aim to graft zwitterionic brush from cellulose membrane (CM) via ARGET-ATRP (Activator Regenerated by Electron Transfer ATRP) method indirectly for blood compatibility improvement. Characterization of the CM substrates before and after modification was carried out by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), water contact angle measurements, X-ray photoelectron spectroscopy analysis, and atomic force microscopy, respectively. The results demonstrated zwitterionic brushes were successfully grafted on the CM surfaces, and the content of the grafted layer increased gradually with the polymerization time. The platelet adhesion, hemolytic test and plasma protein adsorption results indicated the cellulose membrane had significantly excellent blood compatibility featured on lower platelet adhesion and protein adsorption without causing hemolysis. The functionalized cellulose substrate could have a great potential usage for biomedical applications.

Surface-initiated RAFT polymerization of sulfobetaine from cellulose membranes to improve hemocompatibility and antibiofouling property

Two major complications generally occur in blood-contacting devices, namely thrombus formation and microbial invasion and infection. Therefore, hemocompatible and antibiofouling surfaces, which function as barriers to bacterial and cell adhesion, are essential. Herein, we report the successful grafting of zwitterionic polysulfobetaine brushes onto a cellulose membrane (CM) via surface-initiated reversible addition–fragmentation chain-transfer (SI-RAFT) polymerization for improving hemocompatibility and antibiofouling property. Both pristine and polysulfobetaine brush-modified CM substrates were characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), water contact angle measurements (WCA), X-ray photoelectron spectroscopy analysis (XPS), and atomic force microscopy (AFM). Experimental observations demonstrated the successful grafting of polysulfobetaine brushes, where brush thicknesses were found to increase gradually with polymerization time and monomer concentrations. Tests conducted by investigating platelet adhesion, hemolytic rates and protein adsorption indicated that polysulfobetaine brush-grafted CMs had excellent hemocompatibility featuring lower platelet adhesion and protein adsorption properties without causing hemolysis. E. coli adhesion and HeLa cell adhesion tests showed that grafted CMs had superior antibacterial adhesion properties and long-term cell adhesion resistance for up to four days. The functionalized cellulose substrate described holds great potential for use in biomedical applications.

Electrospun polyurethane/keratin/AgNP biocomposite mats for biocompatible and antibacterial wound dressings

Keratin based biomaterials have emerged as potential candidates for various biomedical and biotechnological applications due to their intrinsic biocompatibility, biodegradability, mechanical durability, and natural abundance. The objective of this study is to combine the merits of polyurethane, keratin, and silver nanoparticles (AgNPs) together and develop a novel nanofibrous mat for wound dressing. Herein, keratin was first extracted from human hair and chemically modified with iodoacetic acid to afford S-(carboxymethyl) keratin. The modified keratin was examined using Raman spectroscopy, infrared spectroscopy, and SDS-PAGE. The keratin was then blended with polyurethane (PU) and electrospun. Subsequently, AgNPs were formed in situ to afford antibacterial PU/keratin/AgNP mats. These mats were characterized using field emission scanning electron microscopy (FE-SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), water contact angle measurements, and X-ray photoelectron spectroscopy (XPS). MTT results indicated that the introduction of keratin could accelerate fibroblast cell proliferation, while the loaded AgNPs did not weaken cytocompatibility. Antibacterial test results showed that PU/keratin/AgNP mats exerted good antibacterial property. The results from a wound healing test and a histological examination suggested that these biocomposite mats could remarkably accelerate wound recovery as compared to the conventional gauze sponge dressing. Given their excellent biocompatibility, antibacterial properties, and very mild inflammatory responses, PU/keratin/AgNP mats have great potential for wound dressing applications.

Hemocompatibility and anti-biofouling property improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of zwitterionic cysteine

Inspired by the composition of adhesive proteins in mussels, we used self-polymerized dopamine to form a thin and surface-adherent polydopamine layer onto poly(ethylene terephthalate) (PET) sheet, followed by covalent grafting cysteine (Cys) to improve hemocompatibility and anti-biofouling property. The obtained surfaces were characterized by water contact angle measurements (WCA), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and X-ray photoelectron spectroscopy (XPS) analysis. The results of platelet adhesion and protein adsorption tests showed that cysteine immobilized PET was endowed with improved resistance to nonspecific protein adsorption and platelet adhesion. The results of hemolysis rate test showed cysteine grafted PET (PET-g-Cys) had low hemolytic ability. Cell assay results showed that PET-g-Cys surface could greatly inhibit HeLa cell adhesion. These works provide an ideal hemocompatible and antifouling surface for biomedical applications.

Hemocompatibility improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of zwitterions.

Poly (ethylene terephthalate) (PET) has been widely adopted as a scaffold biomaterial, but further hemocompatibility improvement is still needed for wide biomedical applications. Inspired by the composition of adhesive proteins in mussels, we propose to use self-polymerized dopamine to form a surface-adherent polydopamine layer onto PET sheet, followed by Michael addition with N,N-dimethylethylenediamine (DMDA) to build tertiary amine, and final zwitterions(sulfobetaine and carboxybetaine) construction through ring-opening reaction. Physicochemical properties of substrates were demonstrated by water contact angle measurement, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). The hemocompatibility was evaluated by platelet adhesion, hemolytic, and protein adsorption. The results showed that the zwitterions immobilized PET endowed with improved resistance to nonspecific protein adsorption and platelet adhesion as well as nonhemolytic. The zwitterions with desirable hemocompatibility can be readily tailored to catheter for various biomedical applications.

Preparation and characterization of DOX loaded keratin nanoparticles for pH/GSH dual responsive release

Smart drug carriers are the current need of the hour in controlled drug delivery applications. In this work, pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated through two-step strategies. Keratin nanoparticles were first prepared by desolvation method and chemical crosslinking, followed by electrostatic adsorbing doxorubicin (DOX) to afford drug loaded keratin nanoparticles (KDNPs). The size, size distribution, and morphology of the KDNPs were characterized with dynamic light scattering (DLS) and Scan electronic microscope (SEM). Drug delivery profiles showed that KDNPs exhibited pH and glutathione (GSH) dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting nitric oxide (NO) release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine.

The influence of fiber diameter of electrospun poly(lactic acid) on drug delivery

Electrospinning is a simple process for the production of fibers with diameters in the range from submicron to micron. Herein we aim to explore the influence of fibrous diameter on the drug delivery. The feasible methods by making choice of solvents and changing flow rate were used to prepare 5-fluorouracil-loaded polylactide (PLA) fibers with a large diameter gap. The drug release behavior in vitro was investigated and analyzed in phosphate buffer solution. The drug distribution and fiber diameter both affected the initial burst release. The results showed that all the asspun fibers could not avoid of burst release. The coarse fibers exhibited slight burst release as compared to fine fibers. During the second stage, the fine fibers released faster than that of the coarse fibers. For the whole release stage, the large-diameter fibers seemed to be beneficial for drug release in the long term and smoothly. The MTT results showed that the cytotoxicity of drugs was maintained.

Fabrication of poly(ε-caprolactone)/keratin nanofibrous mats as a potential scaffold for vascular tissue engineering.

The natural abundance of cell adhesion sequences, RGD (Arg-Gly-Asp) and LDV (Leu-Asp-Val) in the keratins make them suitable as biomaterials for tissue engineering applications. Herein, keratins were coelectrospun with poly(ε-caprolactone)(PCL) at the ratio of 9/1, 8/2, and 7/3 to afford nanofibrous mats. The resulting mats were surface-characterized by ATR-FTIR, SEM, WCA, and XPS. Cell attachment data showed that NIH 3T3 cells adhered more to the PCL/keratin nanofibrous mats than the pristine PCL mats. The MTT assay revealed that the PCL/keratin mats had improved cell viability. The blood clotting time test (APTT, PT, and TT) indicated the PCL/keratin mats exerted good blood compatibility. These mats would be a good candidate as a scaffold for vascular tissue engineering.

Differences in cytocompatibility between collagen, gelatin and keratin.

Keratins are cysteine-rich intermediate filament proteins found in the cytoskeleton of the epithelial cells and in the matrix of hair, feathers, wool, nails and horns. The natural abundance of cell adhesion sequences, RGD (Arg-Gly-Asp) and LDV (Leu-Asp-Val), makes them suitable for tissue engineering applications. The purpose of our study is to evaluate their cytocompatibility as compared to well-known collagen and gelatin proteins. Herein, collagen, gelatin and keratin were blended with poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and electrospun to afford nanofibrous mats, respectively. These PHBV/protein composite mats were characterized by field emission scanning electron microscopy (FE-SEM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and dynamic mechanical analysis (DMA). The cytocompatibility was evaluated with cell adhesion, cell viability and cell proliferation. The data from MTT and BrDU revealed that collagen had significantly superior cytocompatibility as compared to gelatin and keratin. Gelatin showed a better cytocompatibility than keratin without statistical significance difference. Finally, we gave the reasons to account for the above conclusions.

Zwitterionic polymer brushes via dopamine-initiated ATRP from PET sheets for improving hemocompatible and antifouling properties.

A low-fouling zwitterionic surface strategy has been proven to be promising and effective for repelling nonspecific adsorption of proteins, cells and bacteria, which may eventually induce adverse pathogenic problems such as thrombosis and infection. Herein, a multi-step process was developed by a combination of mussel-inspired chemistry and surface-initiated atom transfer radical polymerization (SI-ATRP) technique for improving hemocompatible and anti-biofouling properties. Polyethylene terephthalate (PET) sheets were first treated with dopamine, and then the bromoalkyl initiators were immobilized on the poly(dopamine) functionalized surfaces, followed by surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) of 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Subsequently, the resulting PET sheets were ring-opening reacted with 1,3-propiolactone (PL) and 1,3-propanesultone (PS) to afford polycarboxybetaine and polysulfobetaine brushes, respectively. Characterizations of the PET sheets were undertaken by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscope (AFM), water contact angle (WCA) measurements, and X-ray photoelectron spectroscopy (XPS) analysis, respectively. The conversion rates of PDMAEMA to polyzwitterions were evaluated by XPS analysis. The remained PDMAEMA(weak cationic) and formed zwitterions(neutral) would form a synergetic antifouling and antibacterial surface. Hemocompatible and anti-biofouling properties were evaluated by total adsorption of protein as well as the adhesion of platelet, cell and bacterium. Zwitterionic polymer brushes grafted PET sheets showed outstanding hemocompatibility featured on reduced platelet adhesion and repelled protein adsorption. Meanwhile, the grafted PET sheets exerted excellent anti-biofouling property characterized by the resisted adhesion of Escherichia coli and 3T3 cells. In summary, zwitterionic polymer brushed modified PET sheets have a great potential for biomedical applications.