Development and In vitro Evaluation of an RGD-Functionalized Chitosan Derivative for Wound Healing

Abstract

The aim of the work presented in this thesis, was to develop functionalizednanoparticles with the ability to induce adhesion and migration in normal humankeratinocytes. Using particulate systems to promote and support cell adhesion andmigration in epidermal restoration is a novel approach of tissue engineering.In this view, a water-soluble chitosan derivative functionalized with RGD peptideswas developed. Nanoparticles were formed through complex coacervation betweenthe cationic chitosan derivative and the anionic chondroitin sulfate. The particulatesystem was evaluated in vitro for its ability to change phenotype in cells.In the evaluation of the novel hybrid polymer, the successful synthesis wasconfirmed by the absence of cytotoxicity and a preserved bioactivity specific to theRGD-moieties. Both the polymer and the particles formed thereof induced celladhesion and spreading in human dermal fibroblasts, proving the concept ofbioactive nanoparticles. However, when investigating the interaction between thenanoparticles and keratinocytes, no clear conclusion could be drawn and furtherassays are required. To summarize, a bioactive particulate system was developed. The choice of RGDpeptides to induce migration in keratinocytes needs to be re-evaluated and higherconcentrations, mixtures of adhesion peptides or other adhesion peptides might beconsidered for further investigations.