Nanocomposite Hyaluronic Acid based Hydrogel for the Treatment of Esophageal Fistulas

Abstract Fistulas are abnormal connections between two body parts that can impair the quality of life. The use of biological glues represents the least invasive procedure to fill the fistula, however it is limited by the need of multiple injections, the persistence of infection and the failure in the treatment of high-output fistulas. We describe herein the use of an injectable nanocomposite hydrogel able to form in situ a tissue mimicking matrix as an innovative material for the treatment of esophageal fistulas. Injectable hydrogels that have the dual advantage of being implantable with a minimally invasive approach and of adapting their shape to the target cavity, while the introduction of mesoporous silica nanoparticles opens the possibility of drug/biomolecules delivery. The hydrogel is based on hyaluronic acid (HA), the cross-linking process occurs at physiological conditions leading to a hydrogel made of >96% by water and with a large-pore microarchitecture. The kinetic profile of the hydrogel formation is studied as a function of HA molecular weight and concentration with the aim of designing a material that is easily injectable with an endoscopic needle, is formed in a time compatible with the surgical procedure and has final mechanical properties suitable for cell proliferation. The in vivo experiments (porcine model) on esophageal-cutaneous fistulas, showed improved healing in the animals treated with the hydrogel compared with the control group.