ABSTRACT
A pullulan (Pul)-derivative hydrogel was developed by introducing methacrylate (MA) groups and ß-cyclodextrin (ßCD) to form a Pul-ßCD-MA hydrogel by UV cross-linking. The MA was expected to improve the hydrogel's mechanical properties and the ßCD to increase the solubility of curcumin. Pul-ßCD-MA was successfully synthesized, as confirmed by the 1H NMR and FTIR spectra. Hydrogels were formed at Pul-ßCD-MA concentrations of 5 %, 7.5 %, or 10 % w/v. Pul-ßCD-MA showed enhanced curcumin solubility compared to Pul or Pul-MA. The morphological analysis of the hydrogel showed a porous structure. The concentration of ßCD affected the hydrogels' mechanical properties, and the 7.5 % hydrogel (with or without curcumin) did not fracture. The cumulative release of curcumin in the 7.5 % Pul-ßCD-MA hydrogel was 60 % over 8 h. The release profile fit the Korsmeyer-Peppas model. In vitro cytotoxicity tests revealed that hydrogels were biocompatible with human primary dermal fibroblast cells. Curcumin-loaded Pul-ßCD-MA hydrogels significantly accelerated wound healing compared to Pul-ßCD-MA hydrogels without curcumin loading. Therefore, the Pul derivative's hydrogel may be a promising material for wound healing.
Subject(s)
Curcumin , beta-Cyclodextrins , Humans , Hydrogels , Curcumin/pharmacology , Methacrylates , Wound HealingABSTRACT
This study examined the effect of the surface charge of concentrated polymer brush (CPB)-grafted cellulose nanofibers (CNFs) on HepG2 cell flocculation. Four polyelectrolytes, poly(p-styrenesulfonic acid sodium salt) (PSSNa), poly(acrylic acid) (PAA), poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), and poly([(2-methacryloyloxy)ethyl]trimethylammonium chloride) (PMTAC), were grafted onto the CNF surface via surface-initiated atom transfer radical polymerization to form CNF-CPBs. The floc size of HepG2 cells depended on the surface charge of CNF-CPBs, where the anionic CNF-PSSNa formed larger flocs than CNF-PAA; due to the electrostatic repulsive forces, CNF-CPBs with a lower ζ-potential yielded smaller floc sizes. Contrastingly, the cytotoxic cationic CNF-PDMAEMA and CNF-PMTAC limited the floc size growth. Thus, appropriate electrostatic interactions are essential for floc formation and improved cell function in three-dimensional (3D) cell culture systems. Interestingly, while developing a novel 3D cell culture system, we reveal that colloidal flocculation theory is the driving mechanism behind this unique phenomenon.
Subject(s)
Nanofibers , Cellulose , Flocculation , Polymerization , PolymersABSTRACT
In this study, concentrated polymer brush-modified cellulose nanofibers (CNFs) with different fiber lengths were used for the flocculation of cells for systematically studying the mechanism of this unique cellular flocculation based on colloidal flocculation theory. Concentrated poly(p-styrenesulfonic acid sodium salt) brush-grafted CNF (CNF-PSSNa) with different fiber lengths were cultured with three different cell types to examine their influence on floc (cell clusters formed by cellular flocculation) characteristics. The floc size and survival rate could be controlled by modifying the CNF-PSSNa fiber lengths. The three cell types showed the same flocculation tendency after culture, indicating the applicability of the method in different cell lines. After 2 weeks of culture, CNF-PSSNa increased the specific expression of hepatocytes compared to the two-dimensional cell culture. Thus, owing to its wide applicability, high cell viability, and ability to control cell size and improve cell function, this technology could be used as a new three-dimensional cell culture method.
Subject(s)
Nanofibers , Cellulose , Flocculation , PolymersABSTRACT
In order to develop new three-dimensional (3D) cell culture systems for articular cartilage regeneration, concentrated poly(styrene sulfonate sodium salt) brush-modified cellulose nanofibers were employed as building blocks for the self-assembly of human mesenchymal stem cells (hMSCs). Unique 3D cellular structures, such as giant spheres and sheets, were formed by controlling hMSC self-assembly.
Subject(s)
Mesenchymal Stem Cells , Nanofibers , Cellulose/pharmacology , Chondrogenesis , Humans , Nanofibers/chemistry , Polymers/pharmacologyABSTRACT
Concentrated polymer brushes (CPBs) are known to suppress biofouling phenomena, such as protein adsorption and cell adhesion. However, a cumbersome process is needed for their synthesis. Here, we report a simple and versatile method for fabricating nonbiofouling coatings that uses well-defined bottlebrushes instead of CPBs. First, a macroinitiator, poly[2-(2-bromoisobutyryloxy)ethyl methacrylate] (PBIEM), was synthesized by reversible addition-fragmentation chain transfer polymerization. Then, poly[poly(ethylene glycol) methyl ether methacrylate] was grafted from PBIEM through atom transfer radical polymerization to form well-defined bottlebrushes. By controlling the graft chain length, two types of bottlebrushes could be prepared, namely those with a semi-dilute polymer brush (SDPB) structure or a CPB structure on the surface of the outermost layer. Crosslinked films of the bottlebrushes were prepared on silicon wafers by spin-coating and subsequent radical coupling. Importantly, the CPB-type bottlebrush films showed significantly better nonbiofouling characteristics than those of the SDPB-type bottlebrush films.
Subject(s)
Biofouling , Polymers , Adsorption , Biofouling/prevention & control , Cell Adhesion , Methacrylates , Polymerization , Surface PropertiesABSTRACT
The effective control of biointerfacial interactions is of outstanding interest in a broad range of biomedical applications, ranging from cell culture tools to biosensors and implantable medical devices. For many of these applications, highly specific interactions between cells and material surfaces are desired. Sophisticated control over these interactions requires reducing or preventing non-specific interactions on the one hand and displaying highly specific signals that can be recognized by extracellular receptors on the other. We have recently developed ultra-low fouling coatings that can be applied in a single step using photoreactive copolymers of 2-hydroxypropyl acrylamide and N-benzophenone acrylamide. Here, we have expanded this approach by incorporating polymerizable peptide monomers into these copolymers. The monomers QQGWFGAGK(acrylamide) and acrylamide-GAGQQGWF were synthesized after identifying the QQGWF sequence as a binding motif for CD44 by phage display for the first time. Our results demonstrate that UV-crosslinked coatings fabricated using the QQGWFGAGK(acrylamide) monomer are effective at selectively binding hMSC in the presence of HepG2 and HEK293 cells due to the difference in CD44 expression. Our results also demonstrate that the peptide modified coatings retain their low biofouling character using a BCA protein binding assay as well as an E. coli bacterial attachment assay over a 24 h period. Our approach provides an alternative to traditional integrin-mediated selective cell binding on surfaces and opens the door to new diagnostic applications, exploiting the fact that the transmembrane protein CD44 is highly expressed in multiple diseases.
Subject(s)
Biofouling , Escherichia coli , HEK293 Cells , Humans , Hyaluronan Receptors , Peptides , Polymers , Surface PropertiesABSTRACT
The objective of this study is to control and elucidate the mechanism of molecular degradation in a polysaccharide hydrogel. Glycidyl methacrylate (GMA) immobilized dextran (Dex-GMA) was oxidized by periodate to introduce aldehyde groups (oxidized Dex-GMA). The hydrogel was formed by the addition of dithiothreitol to the oxidized Dex-GMA solution through thiol Michael addition with the preservation of the aldehyde group for degradation points. It was experimentally determined that the degradation of this hydrogel can be controlled by the addition of amino groups and the speed of degradation can be controlled independently of mechanical properties because crosslinking and degradation points are different. In addition, the molecular mechanism of the crosslinking between the thiol and aldehyde groups was found to control the degradation of dextran derivatives. It is expected that these results will be beneficial in the design of polymer materials in which the speed of degradation can be precisely controlled. In addition, the cytotoxicity of oxidized Dex-GMA was approximately 3000 times lower than that of glutaraldehyde. The low cytotoxicity of the aldehyde in oxidized Dex-GMA was the likely reason for the harmless functionalized polysaccharide material. Possible future clinical applications include cell scaffolds in regenerative medicine and carriers for drug delivery systems.
ABSTRACT
We proudly present the first organic/inorganic hybrid pullulan/SeNPs hybrid microflower material obtained using a simple and bio-inspired strategy. The chemical structures of pullulan, folic acid decorated cationic pullulan (FA-CP) were designed for stabilizing selenium nanoparticles (SeNPs). SeNPs stabilized by FA-CP hybrid microflowers were observed after the addition of a cysteine hydrochloride solution into the solution mixture of Na2SeO3 and FA-CP. We suggested that the concentrations of cysteine and FA-CP were the key factors for the formation of flower-like structure. In addition, the formation mechanism of the microflowers was tentatively identified as anisotropic hierarchical growth. The microflowers exhibited effective drug adsorption with the loading capacity of 142.2â¯mgâ¯g-1 for doxorubicin which was three times higher than that for the doxorubicin-loaded spherical SeNPs and showed more potent activity against cancer cells while showing less toxicity against normal cells. These data demonstrated that the microflower-like FA-CP/SeNPs structure could be a candidate anticancer drug template in drug delivery systems.