Local injection of a hexametaphosphate formulation reduces heterotopic ossification in vivo.

Heterotopic ossification (HO), the pathological formation of ectopic bone, is a debilitating condition which can cause chronic pain, limit joint movement, and prevent prosthetic limb fitting. The prevalence of this condition has risen in the military population, due to increased survivorship following blast injuries. Current prophylaxes, which aim to target the complex upstream biological pathways, are inconsistently effective â€‹and have a range of side-effects that make them unsuitable for combat-injured personnel. As such, many patients must undergo further surgery to remove the formed ectopic bone. In this study, a non-toxic, U.S. Food and Drug Administration (FDA) -approved calcium chelator, hexametaphosphate (HMP), is explored as a novel treatment paradigm for this condition, which targets the chemical, rather that biological, â€‹bone formation pathways. This approach allows not only prevention of pathological bone formation â€‹but also uniquely facilitates reversal, which current drugs cannot achieve. Targeted, minimally invasive delivery is achieved by loading HMP into an injectable colloidal alginate. These formulations significantly reduce â€‹the length of the ectopic bone formed in a rodent model of HO, with no effect on the adjacent skeletal bone. This study demonstrates the potential of localized dissolution as a new treatment â€‹and an alternative to surgery â€‹for pathological ossification and calcification conditions.

A gellan-based fluid gel carrier to enhance topical spray delivery.

Autologous cell transplantation was introduced to clinical practice nearly four decades ago to enhance burn wound re-epithelialisation. Autologous cultured or uncultured cells are often delivered to the surface in saline-like suspensions. This delivery method is limited because droplets of the sprayed suspension form upon deposition and run across the wound bed, leading to uneven coverage and cell loss. One way to circumvent this problem would be to use a gel-based material to enhance surface retention. Fibrin systems have been explored as co-delivery system with keratinocytes or as adjunct to 'seal' the cells following spray delivery, but the high costs and need for autologous blood has impeded its widespread use. Aside from fibrin gel, which can exhibit variable properties, it has not been possible to develop a gel-based carrier that solidifies on the skin surface. This is because it is challenging to develop a material that is sprayable but gels on contact with the skin surface. The manuscript reports the use of an engineered carrier device to deliver cells via spraying, to enhance retention upon a wound. The device involves shear-structuring of a gelling biopolymer, gellan, during the gelation process; forming a yield-stress fluid with shear-sensitive behaviours, known as a fluid gel. In this study, a formulation of gellan gum fluid gels are reported, formed with from 0.75 or 0.9% (w/v) polymer and varying the salt concentrations. The rheological properties and the propensity of the material to wet a surface were determined for polymer modified and non-polymer modified cell suspensions. The gellan fluid gels had a significantly higher viscosity and contact angle when compared to the non-polymer carrier. Viability of cells was not impeded by encapsulation in the gellan fluid gel or spraying. The shear thinning property of the material enabled it to be applied using an airbrush and spray angle, distance and air pressure were optimised for coverage and viability. STATEMENT OF SIGNIFICANCE: Spray delivery of skin cells has successfully translated to clinical practice. However, it has not yet been widely accepted due to limited retention and disputable cell viability in the wound. Here, we report a method for delivering cells onto wound surfaces using a gellan-based shear-thinning gel system. The viscoelastic properties allow the material to liquefy upon spraying and restructure rapidly on the surface. Our results demonstrate reduced run-off from the surface compared to currently used low-viscosity cell carriers. Moreover, encapsulated cells remain viable throughout the process. Although this paper studies the encapsulation of one cell type, a similar approach could potentially be adopted for other cell types. Our data supports further studies to confirm these results in in vivo models.