PLA and PBAT-based electrospun fibers functionalized with antibacterial bio-based polymers

Antimicrobial fibers based on biodegradable polymers, poly(lactic acid) (PLA), and poly(butylene adipate-co-terephthalate) (PBAT) are prepared by electrospinning. For this purpose, a biodegradable/bio-based polyitaconate containing azoles groups (PTTI) is incorporated at 10 wt.% into the electrospinning formulations. The resulting fibers functionalized with azole moieties are uniform and free of beads. Then, the accessible azole groups are subjected to N-alkylation, treatment that provides cationic azolium groups with antibacterial activity at the surface of fibers. The positive charge density, roughness, and wettability of the cationic fibers are evaluated and compared with flat films. It is confirmed that these parameters exert an important effect on the antimicrobial properties, as well as the length of the alkylating agent and the hydrophobicity of the matrix. The quaternized PLA/PTTI fibers exhibit the highest efficiency against the tested bacteria, yielding a 4-Log reduction against S. aureus and 1.7-Log against MRSA. Then, biocompatibility and bioactivity of the fibers are evaluated in terms of adhesion, morphology and viability of fibroblasts. The results show no cytotoxic effect of the samples, however, a cytostatic effect is appreciated, which is ascribed to the strong electrostatic interactions between the positive charge at the fiber surface and the negative charge of the cell membranes

Biobased polymers derived from itaconic acid bearing clickable groups with potent antibacterial activity and negligible hemolytic activity.

Herein, we report, for the first time, the synthesis of clickable polymers derived from biobased itaconic acid, which was then used for the preparation of novel cationic polymers with antibacterial properties and low hemotoxicity via click chemistry. Itaconic acid (IA) was subjected to chemical modification by incorporating clickable alkyne groups on the carboxylic acids. The resulting monomer with pendant alkyne groups was easily polymerized and copolymerized with dimethyl itaconate (DMI) by radical polymerization. The feed molar ratio of comonomers was varied to precisely tune the content of alkyne groups in the copolymers and the amphiphilic balance. Subsequently, an azide with a thiazole group, which is a component of the vitamin thiamine (B1), was attached onto the polymers by copper-catalyzed azidealkyne cycloaddition (CuAAC) click chemistry leading to triazole linkages. N-Alkylation reactions of the thiazole and triazole groups with methyl and butyl iodides provide the corresponding itaconate derivatives with pendant azolium groups. The copolymers with variable cationic charge densities and hydrophobic/ hydrophilic balances, depending on the comonomer feed ratio, display potent antibacterial activity against Gram-positive bacteria, whereas the activity was almost null against Gram-negative bacteria. Hemotoxicity assays demonstrated that the copolymers exhibited negligible hemolysis and excellent selectivity, more than 1000-fold, for Gram-positive bacteria over human red blood cells.post-print1945 K

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

Antibacterial and compostable polymers derived from biobased itaconic acid as environmentally friendly additives for biopolymers

In this work, a series of antibacterial cationic copolymers derived from bio-sourced itaconic acid was studied as potential biobased active components in biodegradable formulations based on poly(butylene adipate-co-terephthalate) (PBAT) for packaging applications. These copolymers were first characterized by testing their antimicrobial activity against resistant bacterial strains, their biodegradability in compost conditions, and their thermal properties by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The antibacterial properties showed potent activity against Methicillin-resistant Staphylococcus aureus (MRSA), with MIC values as low as 78 μg mL 1. Related to their biodegradability, the cationic polymers biodegraded fast under compost conditions and even a priming effect was observed in the compost. Thermal properties, characterized by DSC and TGA, showed that the copolymers thermally degraded at temperature relatively low; nevertheless, they are able to be processed at temperatures up to ~150 ◦C. Subsequently, these antibacterial polymers were successfully blended as minor active component (10 wt%) with PBAT by melt-extrusion and press-compression molding. The resulting biopolymeric films exhibit potent antibacterial activity, which confirm that the cationic polymers incorporated as active component are able to perverse this activity after the processing and impart antibacterial properties to PBAT bioplastic. Therefore, these antibacterial biobased polymers derived from itaconic acid seem to be good candidates for applications related to active food packaging or even for biomedical devices.MICINNAgencia Estatal de Investigación (AEI, Spain)Fondo Europeo de Desarrollo Regional (FEDER, EU)CSICDepto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu