Novel injectable in-situ forming hydrogel for the treatment of diabetic ulcers

Lower extremity diseases are twice common in diabetic compared with nondiabetic patients, which is known to be related to impaired production of insulin (1). Ulcers frequently become infected, causing great morbidity, and ultimately lower extremity amputation. This work suggests a simple and practical strategy to rebuild the function of tissues in diabetic ulcers using an in situ formed sericin hydrogel, for healing and tissue regeneration, enabling cell recruitment and proliferation. This enzyme-mediated crosslinking hydrogel is capable of gelling in situ by crosslinking polymer hydroxyphenyl groups using horseradish peroxidase (HRP). This system is able to induce fast gelation (~2 min) at physiological temperature (Patent Application (2)). The prepared hydrogels are mainly of amorphous conformation and transparent appearance, stable in PBS (pH 7.4) for 17 days, up to 7 days in protease XIV biological concentration (3.5 U/mg), and 4 days under acute and chronic physiological pH values. These hydrogels will incorporate insulin which is aimed to be released at the diabetic wound site in an attempt to accelerate tissue healing and regeneration. With this, new insights might be found to help explain the connection between diabetes and poor healing. Besides tackling one of today’s major public health issues, this work promotes the re-use and valorization of a textile industrial by-product, sericin, by its integration in the biomedical arena.