A bioactivated nano-layered hydrogel for dermal regeneration in hard-to-heal ulcers

Several strategies have been developed to restore dermal function. These include collagen membranes, decellularized dermis from donors or synthetic graft alternatives. So far, these approaches have been unreliable at best and auto-grafts and transplants (that both create their own problems with donor site morbidity, risk for disease transfer and infections and graft rejection) remain the only predictable method for treating hard-to-heal ulcers today. The major reasons for the failures of these approaches are most probably lack of physical strength combined with poor integration with the subjacent tissues and lack of biological signals that can home in precursor cells (e.g. stem cells and fibroblasts) from surrounding healthy tissues, and finally, the lack of biological signals for epidermis formation. The BioNaNOR project aims at using a dermis-matrix-mimicking hydrogel based on nano-layered and chemically modified chitosan. This artificial dermis analogue will be designed with one “deeper” part that provide biological signals for homing and differentiation of mesoderm derived stem cells, and one “superficial” part that includes molecules that stimulate epithelial cell growth and migration. The nano-layered chitosan matrix is bio-degradable and is ultimately replaced by natural dermal tissue that is later covered by epidermis. During this process, the material slowly releases the embedded bioactive molecules together with chitosan metabolites that are known to favour healing by reducing inflammation and supressing bacterial growth. Moreover, as treatment for hard-to-heal “Full-thickness” ulcers also requires a material that immediately restores and maintain the barrier function and provide tissue strength, stability and elasticity during healing, the BioNaNOR approach include an ultra-strong, nano-layered material that interacts well with the underlaying stratum and restore the tissue barrier until the healing tissues have restored their normal function.

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