Introduction

The present invention consists in the use of a Neuregulin 1 protein conjugated with iron oxide nanoparticles, externally coated in dextran to promote the regeneration of axons in a damaged peripheral nerve. Compared to the protein alone, this conjugate has an enhanced effect in the treatment of these lesions since it increases the stability of the protein and therefore the duration of the action.

Technical features

Peripheral nerve injury affects many people and is due to conditions such as diabetes, hereditary genetic diseases, infectious diseases and inflammatory disorders. The use of tissue engineering and the construction of a regenerative environment can be achieved through a multidisciplinary approach that combines the use of tissue engineering with the construction of an optimized regenerative environment. One of the key aspects is to provide the release of molecules that are able to promote the regeneration of the nerve, and remain stable and active over time.

A specific isoform of Neuregulin 1, a protein essential for the development and regeneration of the nervous system, was conjugated by Michael reaction to iron oxide nanoparticles externally coated with dextran, previously prepared as described in Molday et al, Immunol. Methods 1982; 52 (3): 353-67. This formulation increases the stability of the protein and its stability. Indeed, the conjugate object of the invention has demonstrated prolonged biological efficacy, compared to the unconjugated recombinant protein, in inducing three-dimensional migration. In vitro experiments then demonstrated the biocompatibility of this conjugate, highlighting a rapid cell internalization and subsequent collection in the compartments where iron is demolished and transformed. This long-lasting, biocompatible and non-toxic release system represents a significant improvement with respect to molecules commercially available.

Possible Applications

• Tissue Engineering;
• Peripheral Nerve regeneration.

Advantages

• Improved stability and efficacy of the protein;
• Biocompatibility;
• No Toxicity;
• Single injection;
• Possibility to direct it in situ by applying a local magnetic field in the point where its action is required.