The aging of society and related chronic diseases will predominate in the near future, increasing the costs of health care.

Chronic diseases such as diabetes and cancer are associated with chronic wounds. In addition, surgery and burns often lead to injuries that are difficult to heal. The proposed and patented platform develops nanofibrous scaffolds entirely based on polysaccharides as skin substitutes to achieve healing of such lesions.

The developed scaffolds are based on glycosaminoglycan (chondroitin sulfate or hyaluronic acid) associated to chitosan, pullulan in presence of citric acid and electrospun starting from an aqueous/acetic polymeric solution. The nanofibrous membranes are crosslinked by sterilized heating.

Patent Status

Pending

Priority Number

PCT/IT2017/000160

Priority Date

28/07/2017

License

International

Market

The global advanced wound care market will have a cagr of 4.6% between 2020 and 2024, reaching $ 24.8 billion from $ 19.8 billion in 2019.

Among the key product types, advanced wound dressings are currently leading the global market due to the growing prevalence of acute and chronic wounds, as well as the need for innovative and technologically advanced wound management products.

Problem

In scientific literature, there are many works that have electrospinning as their topic with the aim of preparing “scaffolds” suitable for skin repair. Chitosan is one of the most widely used polymers and also described for this purpose. However, there are no examples of “scaffolds” totally prepared starting from mixtures of hydrosolubile cationic and anionic polysaccharide polymers, capable of forming a poly-electrolytic complex, and electrospun in the absence of organic solvents.

The invention makes it possible to obtain insoluble nanofibers from aqueous polymeric solutions in the absence of toxic organic solvents, avoiding solvent residues in the preparation and allowing an “environmentally friendly” process.

Solvent residues can also adversely affect the interaction with the cells that should proliferate on the membrane.

Another novelty of the invention consists in the possibility of associating polymers with different ionic natures (cationic chitosan and anionic glycosaminoglycans) and being able to electrospin the resulting solution being able to exploit the bioactive properties of all components in the treatment of lesions.

Current technology limits/ solutions

Currently, in the world stage, there are various solutions for the treatment of chronic lesions, from traditional dressings (e.g. cotton gauze or tnt), to advanced dressings (e.g. hydrocolloids based on alginates able to control the hydration of the lesion) up to dermal substitutes (scaffolds for implantation) and skin transplantation. none of these are currently identified as gold standards. in particular, advanced dressings determine very long healing times and expose the lesion to a possible infection for prolonged times, while dermal substitutes have the advantage of being implanted in the lesion and allow to ensure partial or total replacement of the skin covering, in transient or definitive way. however, the latter, which are the most efficient in healing, have a high cost, a protein-based composition (especially collagen) that can give immune reactions, aseptic production and preservation in a hydrated state and at a controlled temperature.

Killer Application

This invention could be exploited in the treatment of the following injuries:

  • Diabetic foot;
  • Venous and / or arterial lesions of the lower limbs;
  • Pressure ulcers;
  • Extensive burns.

Developed products could be registered as:

Medical devices:

– Dermal substitutes (class iii) (systems able to promote the healing of injuries of various kinds as “scaffold”)

– Advanced dressings also loaded with antimicrobials (class iia or iib) (eg silver).

Pharmaceutical:

Therapeutic systems loaded with antimicrobial drugs for promoting healing of acute or chronic infected injuries

Our Technology and Solution

The developed scaffolds are based on glycosaminoglycan (chondroitin sulfate or hyaluronic acid) associated with chitosan and pullulan in the presence of citric acid and electrospun from an aqueous/acetic polymer solution. The nanofibrous membranes are reticulated by heat treatment which can also be used as a sterilization process.

The scaffolds have mechanical properties suitable for in vivo application and support in vitro adhesion and proliferation of fibroblasts and endothelial cells. They have also been shown to promote the healing of skin lesions in an in vivo burn/excision model (rats). The scaffolds can be easily loaded with antimicrobial agents (such as silver) or chemotherapeutic agents (such as norfloxacin). Furthermore, the systems can be reinforced with inorganic particles.

The production by electrospinning uses a simple, single-phase and free of toxic solvents process to obtain ultra-fine, long fibers as a non-woven structure, similar to the extracellular matrix.  The critical quality attributes has been assessed. Moreover, the efficacy of the prototype has been compared to a marked product.

The scale-up is ongoing.

Advantages

  • Use of poorly immunogenic polysaccharide materials;
  • Production without toxic solvents (water / acetic acid);
  • Ease of sterilization (moist heat with standard cycle);
  • Storage at room temperature in the dry state;
  • Ease of sizing;
  • Reduced production cost.
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