ThermoPIGs: Thermoresponsive polymers imitating gelatins for novel healthcare materials

Gelatins are ubiquitous in healthcare, food and cosmetics. The production of gelatin involves isolation of collagen from an animal source, such as pig skin, and its hydrolysis under acidic or basic conditions. A key property of the gelatin produced is its ability to form a stiff hydrogel state which can be melted and cast into the desired geometry. Not only are gelatin’s physical characteristics desirable for the generation of medicines, such as soft gelatin capsules, but they are frequently exploited in cell therapies and in vitro models, for example as scaffolds for 3D culture. These in vitro models form a central pillar of New Approach Methodologies (NAMs) which seek to replace animal models with human-relevant cellular assays to give meaningful toxicological endpoints for novel therapeutics. Working with ImmuONE, a company which designs NAMs, we have recently demonstrated that bovine gelatin is efficacious as a material to stabilise immune cells for the generation of immunocompetent NAMs. Gelatin allows room temperature survival of these immune cells for four days, in theory allowing worldwide shipping at room temperature. However, given the animal source of these gelatins there are ethical and religious concerns around their use as well as significant scientific limitations where the proteins can be immunogenic and contaminants such as pyrogens can cause unwanted reactions to cells. The material properties of gelatin are also limited. Whilst the melting point of porcine gelatin is ca 30-34 °C this process is slow and gelatin typically requires boiling to allow rapid solubilisation, whilst setting the gel at room temperature takes ca 30 minutes.[1] Furthermore, the rheology of gelatin exhibits large hysteresis in heating/cooling cycles. There exists substantial opportunity in the generation of animal-free alternatives to gelatin which avoids the potential for contamination or immune response whilst improving the material properties.