Degradable Cell-Adhesive Hybrid Hydrogels by Cross-Linking of Gelatin with Poly(2-isopropenyl-2-oxazoline).

This study focused on the cross-linking of poly(2-isopropenyl-2-oxazoline) (PiPOx) with gelatin to obtain strong, degradable hybrid hydrogels with good cell adhesion. The molecular weight and concentration of PiPOx and the PiPOx-to-gelatin ratio were varied to adjust the mechanical and swelling properties of the hybrid hydrogels. The swelling degree of PiPOx-gelatin hydrogels in water ranged between 1260 and 810%, with the corresponding Young's compressive moduli ranging from 77 to 215 kPa. Rheological measurements demonstrated the mechanical stability of the hydrogels. The hydrogels exhibited substantial degradation in Dulbecco's phosphate-buffered saline (DPBS) and cell culture medium within several weeks, indicating their degradability and responsiveness. The cell adhesion assay with primary human foreskin fibroblasts revealed the hybrid hydrogels are noncytotoxic and support cell attachment and proliferation. These strong hydrogels thus show excellent potential as biomedical cell scaffolds, combining the tunability and strength of PiPOx hydrogels with gelatin's cell-interactive properties while the ester-containing cross-links provide tunable degradability.

In Vitro Assessment of the Hydrolytic Stability of Poly(2-isopropenyl-2-oxazoline).

Poly(2-isopropenyl-2-oxazoline) (PiPOx) is emerging as a promising, versatile polymer platform to design functional materials and particularly biomaterials that rely on the hydrophilic character of the 2-oxazoline side units. To be able to assess the applicability of PiPOx in a biomedical context, it is essential to understand its stability and degradation behavior in physiological conditions. In the present work, the hydrolytic stability of PiPOx was systematically investigated as a function of pH during incubation in various buffers. PiPOx was found to be stable in deionized water (pH 6.9), to have good stability in basic conditions (pH 8 and 9), to be satisfactorily stable in neutral conditions (pH 7.4), and to have moderate to low stability in acidic conditions (decreases drastically from pH 6 to pH 1.2). At pH 4, PiPOx formed a crosslinked network in a timeframe of hours, while at pH 1.2, PiPOx was transformed to a water-soluble poly(N-(2-hydroxyethyl)methacrylamide) type of structure over the course of 2 weeks. In vitro stability assays were performed in phosphate-buffered saline (pH 7.4), simulated body fluid (SBF) (pH 7.4), simulated saliva (pH 6.4), simulated intestinal fluid (pH 6.8), and plasma (pH 7.4) revealing that PiPOx is stable in these SBFs up to 1 week of incubation. When incubated in simulated gastric fluid (pH 1.2), PiPOx exhibited a similar degradation behavior to that observed in the buffer at pH 1.2, rendering a water-soluble structure. The presented results on the stability of PiPOx will be important for future use of PiPOx for the development of drug-delivery systems and biomedical applications, such as hydrogels.

Simultaneous two and three photon resonant enhancement of third-order NLO susceptibility in an azo-dye functionalized polymer film.

We report the observation of simultaneous two and three photon resonances, enhancing the third-order NLO susceptibility in a thin film of an azo-dye polymer. The possibility of 2-3 orders of magnitude increase in χ((3)) susceptibility is sustained by quantum mechanical calculations. This improves the applications of azo-polymers in all optical signal processing as well as in nonlinear optical imaging.

Cationic amino-acid functionalized polymethacrylamide vectors for siRNA transfection based on modification of poly(2-isopropenyl-2-oxazoline).

Poly(2-isopropenyl-2-oxazoline) (PiPOx) is a functional polymer showing great potential for the development of smart biomaterials. The straightforward synthesis and post-polymerization functionalization of PiPOx offers many opportunities for tailoring the properties of the polymer towards biomaterials. In this study we report for the first time PiPOx-based cationic charged polymethacrylamides with amino acid side chains that can complex siRNA and promote transfection in vitro. Therefore, PiPOx was fully modified via ring opening addition reactions with the carboxylic acid groups of a series of N-Boc-L-amino acids and their reaction kinetics were investigated. Based on the determined kinetic constants, another series of PiPOx-based copolymers with balanced hydrophilic/hydrophobic content of N-Boc-L-amino acids were obtained via one-pot modification reaction with two different N-Boc-L-amino acids. The N-Boc protected homopolymers and related copolymers were deprotected to obtain (co)polymers with the targeted side chain cationic charged units. The (co)polymers' structures were fully investigated via FT-IR and 1H NMR spectroscopy, size exclusion chromatography (SEC), and TGA-DSC-MS analysis. The polarimetry measurements revealed that the homopolymers retain their chiroptical properties after post-modification, and a sign inversion is noticed from (L) N-Boc-protected analogues to (D) for the TFA cationic charged homopolymers. Generally, cationically charged homopolymers with hydrophilic amino acids on the side chain showed efficient complexation of siRNA, but poor transfection while cationic copolymers having both tryptophan and valine or proline side chains revealed moderate siRNA binding, high transfection efficiency (> 90% of the cells) and potent gene silencing with IC50 values down to 5.5 nM. Particularly, these cationic copolymers showed higher gene silencing potency as compared to the commercial JetPRIME® reference, without reducing cell viability in the concentration range used for transfection, making this a very interesting system for in vitro siRNA transfection.

Advances and opportunities in the exciting world of azobenzenes.

Azobenzenes are archetypal molecules that have a central role in fundamental and applied research. Over the course of almost two centuries, the area of azobenzenes has witnessed great achievements; azobenzenes have evolved from simple dyes to 'little engines' and have become ubiquitous in many aspects of our lives, ranging from textiles, cosmetics, food and medicine to energy and photonics. Despite their long history, azobenzenes continue to arouse academic interest, while being intensively produced for industrial purposes, owing to their rich chemistry, versatile and straightforward design, robust photoswitching process and biodegradability. The development of azobenzenes has stimulated the production of new coloured and light-responsive materials with various applications, and their use continues to expand towards new high-tech applications. In this Review, we highlight the latest achievements in the synthesis of red-light-responsive azobenzenes and the emerging application areas of photopharmacology, photoswitchable adhesives and biodegradable materials for drug delivery. We show how the synthetic versatility and adaptive properties of azobenzenes continue to inspire new research directions, with limits imposed only by one's imagination.

Reduction-Responsive Molecularly Imprinted Poly(2-isopropenyl-2-oxazoline) for Controlled Release of Anticancer Agents.

Trigger-responsive materials are capable of controlled drug release in the presence of a specific trigger. Reduction induced drug release is especially interesting as the reductive stress is higher inside cells than in the bloodstream, providing a conceptual controlled release mechanism after cellular uptake. In this work, we report the synthesis of 5-fluorouracil (5-FU) molecularly imprinted polymers (MIPs) based on poly(2-isopropenyl-2-oxazoline) (PiPOx) using 3,3'-dithiodipropionic acid (DTDPA) as a reduction-responsive functional cross-linker. The disulfide bond of DTDPA can be cleaved by the addition of tris(2-carboxyethyl)phosphine (TCEP), leading to a reduction-induced 5-FU release. Adsorption isotherms and kinetics for 5-FU indicate that the adsorption kinetics process for imprinted and non-imprinted adsorbents follows two different kinetic models, thus suggesting that different mechanisms are responsible for adsorption. The release kinetics revealed that the addition of TCEP significantly influenced the release of 5-FU from PiPOx-MIP, whereas for non-imprinted PiPOx, no statistically relevant differences were observed. This work provides a conceptual basis for reduction-induced 5-FU release from molecularly imprinted PiPOx, which in future work may be further developed into MIP nanoparticles for the controlled release of therapeutic agents.