Biodegradable and bioactive nanostructures for skin wounds functional reconstruction – PaNaCee

The aim of the PaNaCée project is to design « biological dressing » for treating skin wounds when their severity requires an urgent intervention, not facilitated by the localization of the operations and by the absence of local hospital or availability of classical treatment.
A recent field of research, based on the development of new biomaterials for delivering therapeutic agents, has appeared as an alternative towards classical tissue reconstruction approach, such as skin graft. These materials include gels, films, fibrillar matrices or particles made of biodegradable or biocompatible polymer and allowing in situ controlled and sustained release of therapeutic drugs or agents. Such release will stimulate or activate specific cellular and biochemical cascades, initiating tissue regeneration by acting at the core of the process.
Another field of research based on nanomedicine is currently exploring antiseptic or antibiotic delivery to prevent infectious contamination of wounds, by the incorporation of nano devices or particles in pre-existing matrix or biomaterials. The PaNaCée project is aiming to bridge these two fields of research. It will develop an innovative therapeutic tool based on biodegradable particles delivering active compounds and distributed along nanofibers that built matrix support; the nanofibers containing antiseptic/antibiotics drugs. In situ incorporation of drugs and growth factors in biodegradable matrices will be the biological part of the dressing and will favor cells colonization in aseptic environment, therefore facilitating rapid wound healing and creation of a functional derma.
A major innovation of this project is in situ controlled release of therapeutic and antiseptic agents included in poly (lactic acid) particles. Inserted in a structure that mimics the extra cellular matrix, they will provide a local microenvironment favoring the functionality of each attracted cell. The second innovation is brought through the use of nanofibrillar matrices created by jet-spraying, and containing antiseptic/antibiotic drugs, with different kinetic of degradation. This project is based on bio-inspired materials, using degradable polymers, and a “safe by design” approach that will facilitate human translational studies. It is worth noticing that a first proof of concept has been obtained by the coordinator’s laboratory. Indeed, in vivo treatment of wounds (mice model) by PLA particles loaded with FGF-2 has been able to favor the functional recovery of dermal skin after healing.
Based on these preliminary results, PaNaCée aims to develop a multifunctional biomaterial, acting as « biological dressing » with controlled properties to favor wound healing and leading to a functional derma in an aseptic environment.
To reach this ambitious program, a consortium able to analyze wound healing, to evaluate scar functionality and to identify specific transcriptomic signatures in ex vivo human skin settings has been created. It includes three academic partners (CNRS, IRBA, INSERM) and a biotechnology SME (Adjuvatis). The working program has been divided in six tasks, (five scientific objectives and one administrative).
The five tasks aim: 1) to design « biological » PLA particles, able to carry either growth factor or anti-oxidant drugs in their core. 2) to design biodegradable matrix containing antiseptic drugs and able to fix the particles for in situ growth factor release in the wound 3) to develop reproducible excision and burn skin wounds in mice models for, 4) in vivo testing of therapeutic efficacy of the biological dressing elaborated in task 2, and lastly to envision ex vivo human testing 5) by applying these methodology on human skin explant. An administrative task devoted to management, dissemination and intellectual properties will be implemented.