Mamoni Dash

Cationic polymers and their therapeutic potential

The last decade has witnessed enormous research focused on cationic polymers. Cationic polymers are the subject of intense research as non-viral gene delivery systems, due to their flexible properties, facile synthesis, robustness and proven gene delivery efficiency. Here, we review the most recent scientific advances in cationic polymers and their derivatives not only for gene delivery purposes but also for various alternative therapeutic applications. An overview of the synthesis and preparation of cationic polymers is provided along with their inherent bioactive and intrinsic therapeutic potential. In addition, cationic polymer based biomedical materials are covered. Major progress in the fields of drug and gene delivery as well as tissue engineering applications is summarized in the present review.

Generation of composites for bone tissue-engineering applications consisting of gellan gum hydrogels mineralized with calcium and magnesium phosphate phases by enzymatic means.

Mineralization of hydrogels, desirable for bone regeneration applications, may be achieved enzymatically by incorporation of alkaline phosphatase (ALP). ALP‐loaded gellan gum (GG) hydrogels were mineralized by incubation in mineralization media containing calcium and/or magnesium glycerophosphate (CaGP, MgGP). Mineralization media with CaGP:MgGP concentrations 0.1:0, 0.075:0.025, 0.05:0.05, 0.025:0.075 and 0:0.1 (all values mol/dm3, denoted A, B, C, D and E, respectively) were compared. Mineral formation was confirmed by IR and Raman, SEM, ICP‐OES, XRD, TEM, SAED, TGA and increases in the the mass fraction of the hydrogel not consisting of water. Ca was incorporated into mineral to a greater extent than Mg in samples mineralized in media A–D. Mg content and amorphicity of mineral formed increased in the order A < B < C < D. Mineral formed in media A and B was calcium‐deficient hydroxyapatite (CDHA). Mineral formed in medium C was a combination of CDHA and an amorphous phase. Mineral formed in medium D was an amorphous phase. Mineral formed in medium E was a combination of crystalline and amorphous MgP. Youngs moduli and storage moduli decreased in dependence of mineralization medium in the order A > B > C > D, but were significantly higher for samples mineralized in medium E. The attachment and vitality of osteoblastic MC3T3‐E1 cells were higher on samples mineralized in media B–E (containing Mg) than in those mineralized in medium A (not containing Mg). All samples underwent degradation and supported the adhesion of RAW 264.7 monocytic cells, and samples mineralized in media A and B supported osteoclast‐like cell formation. Copyright

New antimicrobial chitosan derivatives for wound dressing applications.

Chitosan is a non-toxic, biocompatible, biodegradable natural cationic polymer known for its low imunogenicity, antimicrobial, antioxidant effects and wound-healing activity. To improve its therapeutic potential, new chitosan-sulfonamide derivatives have been designed to develop new wound dressing biomaterials. The structural, morphological and physico-chemical properties of synthesized chitosan derivatives were analyzed by FT-IR, (1)H NMR spectroscopy, scanning electron microscopy, swelling ability and porosity. Antimicrobial, in vivo testing and biodegradation behavior have been also performed. The chitosan derivative membranes showed improved swelling and biodegradation rate, which are important characteristics required for the wound healing process. The antimicrobial assay evidenced that chitosan-based sulfadiazine, sulfadimethoxine and sulfamethoxazole derivatives were the most active. The MTT assay showed that some of chitosan derivatives are nontoxic. Furthermore, the in vivo study on burn wound model induced in Wistar rats demonstrated an improved healing effect and enhanced epithelialization of chitosan-sulfonamide derivatives compared to neat chitosan. The obtained results strongly recommend the use of some of the newly developed chitosan derivatives as antimicrobial wound dressing biomaterials.

Biomimetic Magnetic Silk Scaffolds

Magnetic silk fibroin protein (SFP) scaffolds integrating magnetic materials and featuring magnetic gradients were prepared for potential utility in magnetic-field assisted tissue engineering. Magnetic nanoparticles (MNPs) were introduced into SFP scaffolds via dip-coating methods, resulting in magnetic SFP scaffolds with different strengths of magnetization. Magnetic SFP scaffolds showed excellent hyperthermia properties achieving temperature increases up to 8 °C in about 100 s. The scaffolds were not toxic to osteogenic cells and improved cell adhesion and proliferation. These findings suggest that tailored magnetized silk-based biomaterials can be engineered with interesting features for biomaterials and tissue-engineering applications.

Silk/chitosan biohybrid hydrogels and scaffolds via green technology

Silk fibroin protein-based hydrogels and 3D scaffolds in combinations with chitosan were designed with a focus on green technology. The physico-chemical properties were modulated using ultrasonication processing to avoid the use of organic solvents or chemical crosslinking. The ultrasonication of mixtures of silk and chitosan induced a conformational change of the silk from random coil to β-sheet resulting in the self-assembly of the hydrophobic peptide segments in the protein, entrapping chitosan chains in these silk networks. These biohybrid materials were prepared with different physico-chemical properties by varying the relative concentrations of silk and chitosan. In combination with lyophilization, interconnected porous 3D scaffolds with controlled morphologies were generated. MC3T3-E1 cells were successfully encapsulated in silk fibroin protein and silk fibroin protein–chitosan hydrogels and colonized the scaffolds. These engineered biohybrid hydrogel and scaffold network systems can be utilized to encapsulate bioactive molecules, thus providing a versatile set of biomaterials with retention of degradability, but without the use of organic solvents or chemical crosslinking during preparation.

Multilayered Magnetic Gelatin Membrane Scaffolds

A versatile approach for the design and fabrication of multilayer magnetic scaffolds with tunable magnetic gradients is described. Multilayer magnetic gelatin membrane scaffolds with intrinsic magnetic gradients were designed to encapsulate magnetized bioagents under an externally applied magnetic field for use in magnetic-field-assisted tissue engineering. The temperature of the individual membranes increased up to 43.7 °C under an applied oscillating magnetic field for 70 s by magnetic hyperthermia, enabling the possibility of inducing a thermal gradient inside the final 3D multilayer magnetic scaffolds. On the basis of finite element method simulations, magnetic gelatin membranes with different concentrations of magnetic nanoparticles were assembled into 3D multilayered scaffolds. A magnetic-gradient-controlled distribution of magnetically labeled stem cells was demonstrated in vitro. This magnetic biomaterial-magnetic cell strategy can be expanded to a number of different magnetic biomaterials for various tissue engineering applications.

Curing kinetics of step-index and graded-index single mode polymer self-written waveguides

A low-loss polymer medium to interconnect 2 single mode optical fibers is developed and characterized. It consists of a so-called self-written waveguide (SWW) formed by illuminating a photosensitive polymerization mix with light emanating from the fiber, after which the exposed part polymerizes. Depending on the material system used, this waveguide can have a step index or graded refractive index profile. The fabrication process and its effect on the waveguide performance are explained using an empirical model and afterwards experimentally verified. This approach enables easy process monitoring and optimization, effectively resulting in total insertion losses below 0.3 dB for a single mode fiber-SWW-fiber transition at 1550 nm.

Enzymatic Mineralization of Silk Scaffolds

The present study focuses on the alkaline phosphatase (ALP) mediated formation of apatitic minerals on porous silk fibroin protein (SFP) scaffolds. Porous SFP scaffolds impregnated with different concentrations of ALP are homogeneously mineralized under physiological conditions. The mineral structure is apatite while the structures differ as a function of the ALP concentration. Cellular adhesion, proliferation, and colonization of osteogenic MC3T3 cells improve on the mineralized SFP scaffolds. These findings suggest a simple process to generate mineralized scaffolds that can be used to enhanced bone tissue engineering-related utility.

Silk microgels formed by proteolytic enzyme activity.

The proteolytic enzyme α-chymotrypsin selectively cleaves the amorphous regions of silk fibroin protein (SFP) and allows the crystalline regions to self-assemble into silk microgels (SMGs) at physiological temperature. These microgels consist of lamellar crystals in the micrometer scale, in contrast to the nanometer-scaled crystals in native silkworm fibers. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and zeta potential results demonstrated that α-chymotrypsin utilized only the non-amorphous domains or segments of the heavy chain of SFP to form negatively charged SMGs. The SMGs were characterized in terms of size, charge, structure, morphology, crystallinity, swelling kinetics, water content and thermal properties. The results suggest that the present technique of preparing SMGs by α-chymotrypsin is simple and efficient, and that the prepared SMGs have useful features for studies related to biomaterial and pharmaceutical needs. This process is also an easy way to obtain the amorphous peptide chains for further study.

Enzymatically biomineralized chitosan scaffolds for tissue-engineering applications.

Porous biodegradable scaffolds represent promising candidates for tissue‐engineering applications because of their capability to be preseeded with cells. We report an uncrosslinked chitosan scaffold designed with the aim of inducing and supporting enzyme‐mediated formation of apatite minerals in the absence of osteogenic growth factors. To realize this, natural enzyme alkaline phosphatase (ALP) was incorporated into uncrosslinked chitosan scaffolds. The uncrosslinked chitosan makes available amine and alcohol functionalities to enhance the biomineralization process. The physicochemical findings revealed homogeneous mineralization, with the phase structure of the formed minerals resembling that of apatite at low mineral concentrations, and similar to dicalcium phosphate dihydrate (DCPD) with increasing ALP content. The MC3T3 cell activity clearly showed that the mineralization of the chitosan scaffolds was effective in improving cellular adhesion, proliferation and colonization. Copyright