Development of composite hydrogel based on hydroxyapatite mineralization over pectin reinforced with cellulose nanocrystal.

Hydrogels based on pectin and cellulose nanocrystals (CNC) were used in our study to nucleation and growth of hydroxyapatite (HAp) by the biomimetic method. In this study, we evaluated the direct impact of the different percentages of CNC on pectin hydrogel and the influence of HAp obtained through two methods. CNC were obtained from HCl hydrolysis following chemical functionalization through vinyl groups. The percentage of CNC positively induces thermal stability, mechanical properties and HAp mineralization from biomimetic using simulated body fluid (1.5 SBF). Hydrogels with 5% of CNC showed a higher amount of HAp immersed for 14 days, about 28% of HAp. The obtained hydrogels were compared with hydrogels containing 20% of HAp nanoparticles obtained by chemical precipitation. Biocompatibility of the hydrogels was evaluated by cell viability using fibroblasts (L929). In general, the hydrogels obtained through the biomimetic method show slightly larger biocompatibility compared to the hybrid hydrogels obtained from chemical precipitation.

pH-responsive hybrid hydrogels: Chondroitin sulfate/casein trapped silica nanospheres for controlled drug release.

In this study, the materials were synthesized by chemically crosslinking chondroitin sulfate (CS), casein (CAS), and silica nanospheres (SiO2), creating a highly crosslinked network. The hydrogel release profile was adaptable (that is, it could be faster or slower as needed) simply by changing the polymeric proportion. The incorporation of 5% of silica nanospheres, in mass, for all CAS/CS matrices promoted a better-controlled and sustained release of l-dopa, focusing on the matrix based on 70% of CAS, 30% of CS and 5% of silica, whose l-dopa release lasted for 87 h. Besides, hydrogels are cytocompatible. These new hydrogels can be considered highly attractive materials to be used for controlled and sustained drug release purposes, as well as scaffolds and wound dressing systems.

Two-dimensional thermoresponsive sub-microporous substrate for accelerated cell tissue growth and facile detachment.

Thermoresponsive sub-microporous films having a lower critical solution temperature (LCST), promptly obtained by using the breath figure method, were applied to tissue engineering. These sub-microporous films, sized 100-400 nm, were prepared by blending poly(N-isopropylacrylamide) (PNIPAAm) with polystyrene (PS), in addition to applying the dynamic breath figure (BF) method. The thermoresponsive blends were prepared with polyethylene terephthalate (PET) substrate by using a spin coater; the pore size was modulated according to the spin speed. The sub-microporous films, either with pure PNIPAAm or with different PNIPAAm contents were applied as substrates in order to obtain cell growth (Vero cells); moreover, the effect of PNIPAAm use was evaluated. The PNIPAAm sub-microporous films made the cellular viability to be 9-13-fold higher than the control sample commonly used in cell culture. In addition, the thermoresponsive PNIPAAm properties were even noticed at a low PNIPAAm content in the porous films. Such polymer system was successfully applied to detach the Vero cell tissue using temperature variation.

Heparosan as a potential alternative to hyaluronic acid for the design of biopolymer-based nanovectors for anticancer therapy.

Glycosaminoglycans (GAGs) are important components of the extracellular matrix that have attracted great interest for drug delivery and pharmaceutical applications due to their diverse biological functions. Among GAGs, heparosan (Hep), a biosynthetic precursor of heparin, has recently emerged as a promising building block for the design of nanoparticles with stealth properties. Though this non-sulfated polysaccharide has a chemical structure very close to that of hyaluronic acid (HA), it distinguishes from HA in that it is biologically inert in the extracellular spaces in the body. In this study, we designed Hep- and HA-based nanogels (NGs) that differ only in the chemical nature of the hydrophilic shell. The nanogels were prepared in a very straightforward way from Hep and HA modified with a thermoresponsive copolymer properly designed to induce self-assembly below room temperature. This versatile synthetic approach also enabled further shell-crosslinking allowing an increase in the colloidal stability. After careful characterization of the un-crosslinked and crosslinked Hep and HA NGs in terms of size (Z-average diameters of un-crosslinked and crosslinked NGs ∼110 and 150 nm) and morphology, they were injected intravenously into tumor-bearing mice for biodistribution experiments. Interestingly, these show that the liver uptake of Hep nanogels is remarkably reduced and tumor accumulation significantly improved as compared to HA nanogels (intensity ratios of tumor-to-liver of 2.2 and 1.4 for the un-crosslinked and crosslinked Hep NGs versus 0.11 for the un-crosslinked and crosslinked HA ones). These results highlight the key role played by the shell-forming GAGs on the in vivo fate of nanogels, which correlates with the specific biological properties of Hep and HA.

Antibacterial Performance of a PCL-PDMAEMA Blend Nanofiber-Based Scaffold Enhanced with Immobilized Silver Nanoparticles.

In the present study, nanofiber meshes (NFs), composed of polycaprolactone and poly[(2-dimethylamino)ethyl methacrylate] at 80/20 and 50/50 PCL/PDMAEMA blend ratios, were obtained through electrospinning. Silver nanoparticles (AgNPs) formed in situ were then immobilized on NF surfaces through adsorption processes at different pHs. It was possible to observe that the amount of NF-AgNPs can be tuned by changing the pH of AgNPs immobilization and the PCL/PDMAEMA ratio in the blend. The neat NF and NF-AgNPs were characterized with respect to their morphology and mechanical properties. The effects of AgNPs on the antibacterial activities and cytotoxicity of meshes were also evaluated. The antibacterial performance of such NF was improved by the presence of AgNPs. The NF-AgNPs presented good antibacterial effect against S. aureus and partial toxicity against E. coli and P. aeruginosa. Also, compared with neat PCL/PDMAEMA the NF-AgNPs presented lower cytotoxicity against VERO cells, showing their potential for applications in tissue engineering for different types of cell growth.

Controlling cell growth with tailorable 2D nanoholes arrays.

A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin polymer films is demonstrated. The formation of the pores in the polymer films involves breath figure phenomenon and occurs during the film deposition by spin coating. The formation of nanoporous thin films takes only few seconds, and the method does not require complex equipment or expensive chemicals. This method also constitutes a straightforward approach to control the size of the pores formed in thin films. Besides allowing control over the average pore size of the porous films, the use of dynamic deposition with the breath figure phenomenon causes the reduction in the pore size to nanometer scale. The nanoporous arrays obtained by the breath figure are applied as substrates for cell growth, and the effect of their nanopore size on cell growth was evaluated. Notably, it is found that cell viability is related to pore size, where 2D nanoporous structure is more beneficial for cell culture than 2D microporous structures. The change in the average pore size of the polymer films from 1.22 µm to 346 nm results in a threefold increase in cell viability.

Polyelectrolyte complexes of poly[(2-dimethylamino) ethyl methacrylate]/chondroitin sulfate obtained at different pHs: I. Preparation, characterization, cytotoxicity and controlled release of chondroitin sulfate.

For the first time, polyelectrolyte complex based on poly[(2-dimethylamino) ethyl methacrylate] (PDMAEMA) and chondroitin sulfate (CS) was prepared. The properties of novel material and precursors were investigated by WAXS, FTIR, TGA, SEM and DLS analysis. The PDMAEMA/CS PECs presented hydrophilic-hydrophobic transition at pHs 6.0, 7.0 and 8.0 whereas the non-complexed PDMAEMA showed such a transition at pH 8.0 and not at pHs 6.0 and 7.0. Studies of CS release from PECs at pHs 6 and 8 confirmed that the samples possess the potential to release the CS in alkaline and not in acidic conditions. Since PECs are thermo-responsive due to the reduction of LCST caused by the increase in pH, the release of CS was dependent on temperature and pH factors. Cytotoxicity assays using healthy VERO cells showed that the complexation between CS and PDMAEMA increased the PECs' biocompatibility related to PDMAEMA. However, the biocompatibility depends on the amount of CS present in the PECs.