Design of Immune Modulating Dendritic Networks for future treatment of Diabetic Foot Ulcers

Descripción del proyecto

Redes dendríticas catiónicas para el tratamiento de la úlcera del pie diabético

Las úlceras del pie diabético (UPD) son complicaciones costosas de la diabetes que representan una carga significativa para los pacientes y los sistemas sanitarios. Los apósitos convencionales suelen ser poco efectivos para tratar estas úlceras. Los polímeros dendríticos hiperramificados ofrecen ventajas como la mejora de las interacciones, la baja viscosidad y la rentabilidad. En el proyecto HYPERNET, financiado por las acciones Marie Skłodowska-Curie, se pretende desarrollar redes dendríticas catiónicas para combatir las infecciones y mejorar la modulación inmunitaria durante la cicatrización de las UPD. El equipo del proyecto sintetizará copolímeros dendrítico-lineales-dendríticos hiperramificados catiónicos a partir de polietilenglicol y ácido 2,2-bis(metilol) propiónico que, a continuación, se hibridarán con colágeno para crear nanoplataformas dendríticas catiónicas para la liberación localizada de insulina. Estas redes catiónicas actúan como agentes antibacterianos, mientras que el colágeno, la insulina y las estructuras dendríticas contribuyen a la modulación del sistema inmunitario.

Objetivo

Diabetic foot ulcers (DFU) are one of the most severe and costly long-term diabetic complications, causing a considerable financial burden to patients and healthcare sectors globally. Most commercial wound dressing materials are based on linear natural or synthetic polymers, and they are not capable of treating DFU efficiently. Innovative material design and therapeutic methodologies are critical to provide improved treatments for DFU. Hyperbranched dendritic polymers show advantages of having multiple terminal groups for multivalent interactions, low viscosity, cost-effectiveness and large-scale production in high yield, which are important features in practical biomedical applications. The aim of this proposal is to develop advanced cationic dendritic networks (CDNs) which are designed to eliminate infections and stimulate favorable immune modulation during the DFU healing process. In this context, a library of cationic heterofunctional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) based on polyethylene glycol (PEG) and 2,2-bismethylol propionic acid (bis-MPA) will be synthesized and hybridized with collagen to fabricate well-defined CDNs to deliver insulin locally for improving DFU treatment. The cations will provide long-term antibacterial activity; collagen, insulin and the dendritic structures and cationic charges are envisioned to provide the immune modulation during DFU healing process. I will study the effects of the CDNs on skin cells at molecular level, and identify functional groups and structures of materials that can actively promote DFU healing. Proof-of concept wound dressings will be designed based on the material properties and gelation mechanism, and methods for large scale production of the optimized hydrogels will be explored. It is promising that this project will provide a better treatment for DFU and potentially other chronic wounds.