Julien Picard

Controlled remodeling of a protein-polysaccharide mixed gel: examples of gelatin-hyaluronic acid mixtures

The gelation of gelatin was studied in the presence of a polysaccharide, hyaluronic acid through rheology measurements. The influence of the polysaccharide on the obtaining of two different gel networks was evaluated: a chemical gel due to enzyme-catalyzed covalent bonding and of a physical gel due to triple helix formation induced by a temperature decrease were both formed in presence of hyaluronic acid. At the liquid state, the rheological properties (shear thinning/viscoelasticity) of the protein-polysaccharide mixture are dictated by the polysaccharide while gelatin modifies viscosity only from a quantitative point of view. Hyaluronic acid does not modify the gelation mechanism of gelatin. It is mainly present in the sol phase of the protein gel where it induces an entangled state which influences the overall viscoelasticity of the system. The impact of the polysaccharide enzymatic degradation on the mechanical properties of the mixture has been evaluated. Hyaluronidase allows a controlled modification of the loss modulus without affecting the storage modulus of gelatin gels. These experiments demonstrate that the mechanical properties of a mixed hydrogel can be a controlled through enzymatic remodeling.

Gelatin‐Alginate Gels and Their Enzymatic Modifications: Controlling the Delivery of Small Molecules

The release of molecules entrapped within biogels is dictated by diffusion laws. Innovative biogel architectures are conceived and tested to control small molecule delivery from gelatin gels. The ionic interactions modulate the release of small molecules. Alginate is then added to gelatin gels and further hydrolyzed; the influence of viscosity is discussed. Next, various mixed gels are compared, such as a gelatin-alginate IPN and the original architecture of an alginate gel entrapped in a gelatin gel with or without a polysaccharidase. The relative influence of ionic interactions and diffusional constraints on the delivery of small charged molecules is explored, and a solution for controlling diffusion is proposed for any situation.

Mastered proteolysis of gelatin gel can control delivery kinetics of entrapped large molecules

Biogels are useful reservoirs for molecular delivery as they can entrap a large variety of compounds in their liquid phase. The delivery kinetics of these molecules is dictated by diffusion laws and thus depends on their molecular size. An original strategy to accelerate the release of large molecules from a gelatin gel is here described. The gel solid network is progressively degraded by enzymes which allows for the delivery of large to very large molecules in a well-controlled way. Diffusion by burst is thus made possible even for very large molecules. Finally, a mathematical model is elaborated to predict the diffusion of molecules entrapped inside a gel undergoing a gel–sol transition.

Ephemeral biogels to control anti-biofilm agent delivery: From conception to the construction of an active dressing

Chronic wound colonization by bacterial biofilms is common and can cause various complications. An anti-biofilm strategy was developed around the co-entrapment of a commercially available antiseptic, PHMB (polyhexamethylene biguanide 4mgmL-1), with EDTA (Ethylen diamine tetra acetic acid, 20mM) in a gelatin gel. The two active compounds act synergistically against bacterial biofilms, but their efficiency is strongly reduced (16-fold) when entrapped inside the 5% gelatin gel, and they weaken the mechanical properties (50-fold) of the gel. Increasing the gelatin concentration to 7% allows for good mechanical properties but large diffusional constraints. An active ephemeral gel, a chemical gel with controlled hydrolysis, was conceived and developed. When the ephemeral gel was solubilized after 48h, PHMB delivery increased, leading to good anti-biofilm activity. The various gels were examined over 24 and 48h of contact with P. aeruginosa and S. aureus biofilms, two types of bacterial biofilms frequently encountered in chronic wounds. The ephemeral gel eradicated the dense biofilms (>6.107CFU·cm-2) produced by either single or mixed strains; a similar efficiency was measured for biofilms from strains of both laboratory and clinical origin. The formulation was then adapted to develop a dressing prototype that is active against biofilms and fulfils the requirements of an efficient wound care system.