Boronic acid and diol-containing polymers: how to choose the correct couple to form "strong" hydrogels at physiological pH.

Dynamic covalent hydrogels crosslinked by boronate ester bonds are promising materials for biomedical applications. However, little is known about the impact of the crosslink structure on the mechanical behaviour of the resulting network. Herein, we provide a mechanistic study on boronate ester crosslinking upon mixing hyaluronic acid (HA) backbones modified, on the one hand, with two different arylboronic acids, and on the other hand, with three different saccharide units. Combining rheology, NMR and computational analysis, we demonstrate that carefully selecting the arylboronic-polyol couple allows for tuning the thermodynamics and molecular exchange kinetics of the boronate ester bond, thereby controlling the rheological properties of the gel. In particular, we report the formation of "strong" gels (i.e. featuring slow relaxation dynamics) through the formation of original complex structures (tridentate or bidentate complexes). These findings offer new prospects for the rational design of hydrogel scaffolds with tailored mechanical response.

Injectable Self-Healing Hydrogels Based on Boronate Ester Formation between Hyaluronic Acid Partners Modified with Benzoxaborin Derivatives and Saccharides.

We demonstrate here, for the first time, formation of injectable dynamic covalent hydrogels at physiological pH using benzoxaborin-saccharide complexation as a reversible cross-linking method. The gels were prepared by simply mixing hyaluronic acid modified with an original boronic acid derivative, 3,4-dihydro-2H-benzo[e][1,2]oxaborinin-2-ol (1,2-ABORIN), and HA functionalized with 1-amino-1-deoxy-d-fructose. Dynamic rheological experiments confirmed the gel-like behavior (storage modulus (G') > loss modulus (G″) in the frequency window explored) for the designed HA-1,2-ABORIN/HA-fructose network. Furthermore, this hydrogel exhibited excellent self-healing and injectability behaviors in aqueous conditions and was found to be responsive to pH. Additionally, fibroblast cells encapsulated in the HA network showed high viability (>80% after 7 days of cell culture), as monitored by Live/Dead staining. Taken together, this new class of boronate ester cross-linked hydrogel provides promising future for diverse biomedical applications.

Reversible Bioconjugation: Biodegradable Poly(phosphate)-Protein Conjugates.

Protein-polymer conjugates are widely used to improve the pharmacokinetic properties of therapeutic proteins. Commercially available conjugates employ poly(ethylene glycol) (PEG) as the protective polymer; however, PEG has a number of shortcomings, including non-biodegradability and immunogenicity, that call for the development of alternatives. Here, the synthesis of biodegradable poly(phosphate), that is, poly(ethyl ethylene phosphate) (PEEP), by organo-catalyzed anionic ring-opening polymerization exhibiting dispersity values Ð < 1.3 is reported. Polymers with molecular weights between 2000 and 33 200 g mol-1 are then ω-functionalized with a succinimidyl carbonate group and subsequently conjugated to model proteins. These are the first conjugates based on polyphosphates which degraded upon exposure to phosphodiesterase. As is the case for PEGylated therapeutics, residual in vitro activity of the PPEylated conjugates depends on the extent of protein modification. These results suggest that PEEP exhibits the desired properties of a biopolymer for use in next generation, fully degradable drug delivery systems.

A study of the effects of aeration and agitation on the properties and production of xanthan gum from crude glycerin derived from biodiesel using the response surface methodology.

The effects of aeration and agitation on the properties and production of xanthan gum from crude glycerin biodiesel (CGB) by Xanthomonas campestris mangiferaeindicae 2103 were investigated and optimized using a response surface methodology. The xanthan gum was produced from CGB in a bioreactor at 28 °C for 120 h. Optimization procedures indicated that 0.97 vvm at 497.76 rpm resulted in a xanthan gum production of 5.59 g L(-1) and 1.05 vvm at 484.75 rpm maximized the biomass to 3.26 g L(-1). Moreover, the combination of 1.05 vvm at 499.40 rpm maximized the viscosity of xanthan at 0.5% (m/v), 25 °C, and 25 s(-1) (255.40 mPa s). The other responses did not generate predictive models. Low agitation contributed to the increase of xanthan gum production, biomass, viscosity, molecular mass, and the pyruvic acid concentration. Increases in the agitation contributed to the formation of xanthan gum with high mannose concentration. Decreases in the aeration contributed to the xanthan gum production and the formation of biopolymer with high mannose and glucose concentrations. Increases in aeration contributed to increased biomass, viscosity, and formation of xanthan gum with greater resistance to thermal degradation. Overall, aeration and agitation of CGB fermentation significantly influenced the production of xanthan gum and its properties.