Magnetic-responsive polysaccharide hydrogels as smart biomaterials: Synthesis, properties, and biomedical applications.

This review reports recent advances in polysaccharide-based magnetic hydrogels as smart platforms for different biomedical applications. These hydrogels have proved to be excellent, viable, eco-friendly alternative materials for the biomedical field due to their biocompatibility, biodegradability, and possibility of controlling delivery processes via modulation of the remote magnetic field. We first present their main synthesis methods and compare their advantages and disadvantages. Next, the synergic properties of hydrogels prepared with polysaccharides and magnetic nanoparticles (MNPs) are discussed. Finally, we describe the main contributions of polysaccharide-based magnetic hydrogels in the targeted drug delivery, tissue regeneration, and hyperthermia therapy fields. Overall, this review aims to motivate the synthesis of novel composite biomaterials, based on the combination of magnetic nanoparticles and natural polysaccharides, to overcome challenges that still exist in the treatment of several diseases.

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.

Enhancing Near-Infrared Photothermal Efficiency of Biocompatible Flame-Synthesized Carbon Nano-Onions with Metal Dopants and Silica Coating.

As an alternative to eliminating cancer cells with minimal impacts on the nearby tissues, biocompatible nanoparticles based on silica-coated carbon nano-onions, with outstanding photothermal efficiency, are presented. Metal-doped carbon nano-onion@SiO2 materials are produced using flame synthesis. Metal complexes are injected in the flame to tune the carbon organization levels, which results in materials with excellent photostability and total photothermal conversion efficiency, regarding the incident light input, as higher as 48% for 785 nm laser. It was found that the metal dopant, even at a very low content, plays an interesting role in photothermal efficiency. We tested the effect of thin silica layers on the carbon nanosphere, first as a way to improve biocompatibility and provide a more reactive surface toward the modifications process to add vectorizing agents. Despite the primary goal of the silica shell, a notable increase in photothermal efficiency was observed. In vivo studies of the biological response to the materials as probed by the zebrafish model found that the as-prepared carbon nanospheres and the SiO2-coated particles are highly biocompatible. The SiO2-coated samples were found to be more suitable for photothermal application, due to the higher colloidal stability and higher photothermal efficiency.

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.

Biomimetic nanocomposite based on hydroxyapatite mineralization over chemically modified cellulose nanowhiskers: An active platform for osteoblast proliferation.

Functionalized-cellulose nanowhiskers (CNWs) were obtained and used to improve hydroxyapatite (HAp) growth by the biomimetic method. CNWs were obtained through HCl hydrolysis and then submitted to chemical functionalization with carboxylate or amine groups that can induce selective HAp mineralization efficiently. Functionalized-CNWs were tested against HAp growth through the biomimetic method using a simulated body fluid (SBF) as a medium during 14 and 28 days of mineralization. Both chemical surface nature (bearing carboxylate or amine reactive groups) and contact time with SBF influenced the nucleation and growth of HAp crystals over CNWs surface. Nanocomposites immersed for 28 days showed a higher amount of HAp crystals compared to bare CNWs or the ones immersed for 14 days. Biocompatibility of the nanomaterials immersed for 14 days in SBF was evaluated through cell viability test using pre-osteoblasts (MC3T3-E1). In general, functionalized-CNWs containing HAp crystals deposited through biomimetic method showed promising results, with CNWs bearing amine groups showing a slightly larger biocompatibility compared to the ones bearing carboxylate groups during an incubation period of 24 h.

Water Droplet Self-Assembly to Au Nanoporous Films with Special Light Trapping and Surface Electromagnetic Field Enhancement.

Gold nano "breath figure" films are for the first time reported and their function as ideal systems for plasmonics demonstrated. Metal nano-breath figure substrates are metal thin films containing nanohole arrays supported on a solid substrate. Au nanohole arrays are prepared from the dynamic breath figure phenomenon, in which the pore formation is controlled to provide holes smaller than 100 nm. Au layer is deposited on polymer substrates containing breath figure topology. The breath figure topology can be fully translated to the Au layer. The nanofabrication process is completed within few minutes. A simplified preparation process but very impressive light trapping and surface electromagnetic field enhancement are related to the Au breath figure films obtained in this work. The porous films demonstrated higher absorbance in the region of 500-1100 nm than nonporous Au films. In the case of 10 nm Au film, the plasmon absorbance becomes more intense than the electronic band absorbance. The electromagnetic enhancement is proved by surface enhanced Raman spectroscopy effect, which is found to be very close to the maximum possible value predicted for nonresonant species.

Cellulose nanowhiskers decorated with silver nanoparticles as an additive to antibacterial polymers membranes fabricated by electrospinning.

Antimicrobial films based on distinct polymer matrices, poly (vinyl alcohol) (PVA) or poly (N-isopropylacrylamide) (PNIPAAm), and silver nanoparticles (AgNPs) immobilized onto cellulose nanowhiskers (CWs) were successfully prepared by either casting or electrospinning. CWs were first functionalized with carboxylate groups (labeled as CWSAc) and later they were immersed in a silver nitrate solution (AgNO3). After Ag+ ions anchored in the COO- groups are chemically reduced to produce AgNPs. The CWSAc/AgNPs biological activity was evaluated against Staphylococcus aureus (S. aureus), Bacillus Subtilis (B. subtilis), Escherichia coli (E. coli), and Candida albicans (C. albicans). The materials were more effective against C. albicans that showed a MIC of 15.6 µg/mL. In the process of AgNPs synthesis, the activity of the stabilizing agent (gelatin) and concentration of precursor and reducing agents were evaluated. The synthesized polymeric films displayed good antimicrobial activity against S. aureus, E. coli, and Pseudomonas aeruginosa (P. aeruginosa) bacteria. The PVA films with CWSAc/AgNPs showed diameter of the inhibition halo of up to 11 mm. The results obtained displayed that the films obtained have a potential application to be used in different fields such as packaging, membrane filtration, wound dressing, clothing and in different biomedical applications.

Mechanically improved polyvinyl alcohol-composite films using modified cellulose nanowhiskers as nano-reinforcement.

Cellulose nanowhiskers (CWs) extracted from cotton fibers were successfully modified with distinct anhydrides structures and used as additives in poly(vinyl alcohol) (PVA) nanocomposite films. The surface modification of CWs was performed with maleic, succinic, acetic or phthalic anhydride to compare the interaction and action the carboxylic groups into PVA films and how these groups influence in mechanical properties of the nanocomposites. CWs presented a high degree of crystallinity and good dispersion in water, with average length at the nanoscale. The addition of specific amounts (3, 6 and 9 wt.%) of modified-CWs increased up to 4.4 times the storage modulus (PVA88-CWSA 9 wt.%), as observed from dynamic mechanical analysis (DMA), compared to the bare PVA films. A significant increase in mechanical properties such as tensile strength, elastic modulus, and elongation at break showed a close relationship to the amount and chemical surface characteristics of CWs added, suggesting that these modified-CWs could be explored as reinforcement additives in PVA films.

The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure.

This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system. A quantitative 6-month stability study showed that the inclusion of chitosan in PCL NPs did not induce a change in adsorbed ovalbumin (OVA) secondary structure characterized by the increase in the unordered conformation (random coil), as it was observed for OVA adsorbed to chitosan NPs. Additionally, the slight conformational changes occurred, are not expected to compromise ovalbumin secondary structure and activity, during a 6-month storage even at high temperatures (45°C). In simulated biological fluids, PCL/chitosan NPs showed an advantageous release profile for oral delivery. Overall, the combination of PCL and chitosan characteristics provide PCL/chitosan NPs valuable features particularly important to the development of vaccines for developing countries, where it is difficult to ensure cold chain transportation and non-parenteral formulations would be preferred.

Hybrid materials for bone tissue engineering from biomimetic growth of hydroxiapatite on cellulose nanowhiskers.

Cellulose nanowhiskers (CNWs) with different surface composition were used to generate the biomimetic growth hydroxyapatite (HAp). Hybrids materials primarily consist of CNWs with HAp content below 24%. CNWs were produced by different inorganic acid hydrolyses to generate cellulose particles with surface groups to induce HAp mineralization. In the present study, we evaluate the use of CNWs prepared from hydrochloric acid, sulfuric acid and phosphoric acid. HAp growth was obtained from the biomimetic method using a simulated body fluid concentration of 1.5M (SBF). The sulfonate and phosphonate groups on the CNW surface have a direct impact on the nucleation and growth of HAp. HAp/CNW were also compared with the physical mixture method using HAp nanoparticles prepared by chemical precipitation. The bioactivity and biocompatibility of the hybrid materials were assessed by cell viability studies using fibroblast cells (L929). The materials obtained from the biomimetic method have superior biocompatibility/bioactivity compared to the material synthesized by the wet chemical precipitation method with an incubation period of 24h.

Covalently-layers of PVA and PAA and in situ formed Ag nanoparticles as versatile antimicrobial surfaces.

The in situ synthesis of silver nanoparticles (AgNPs) within covalently-modified poly(ethylene terephthalate) (PET) films possessing ultra-thin layer of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) is successfully demonstrated. The resulting polymeric films are shown to exhibit antimicrobial activities toward Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungus (Candida albicans). To make the films, first PET surfaces were subject to photo-oxidation and subsequent solid-state grafting to attach a PVA layer, followed by a PAA layer. To synthesize the AgNPs inside the films, the PVA and PAA-modified PET was soaked in AgNO3 solution and the polymeric film was modified with the Ag(+) ions via Ag(+)-carboxylate interaction, and then the Ag(+) ions-containing polymer film was subject to either photo-reduction or thermal reduction processes. The PVA and PAA thin layers attached by covalent bonds to the PET surface uniquely promoted not only the in situ synthesis but also the stabilization of AgNPs. The formation of the AgNPs was confirmed by UV-vis spectroscopy or by monitoring the surface plasmon resonance (SPR) peak associated with AgNPs. The resulting PVA and PAA ultrathin layers modified and AgNPs containing PET served as bactericide and fungicide, inhibiting the growth of bacteria and fungi on the surfaces. Given PET's versatility and common use in many commercial processes, the method can be used for producing plastic surfaces with versatile antimicrobial and antibacterial properties.

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.