The BIOHYBRID consortium was build up with the overall aim to develop, in a preclinical perspective, an innovative biohybrid artificial nerve device for the regenerative treatment of traumatic injuries of peripheral nerves. This consortium consists of three active and well integrated SMEs as well as six academic partners that are recognised leaders in the scientific areas of interest for this project. Furthermore, another partner has substantiated expertises to meet the regulatory work for ATMP development.
Traumatic injuries of peripheral nerves represent a major cause for morbidity and morbility
in Europe and their social impact is considerably high. It has been estimated that the incidence of peripheral nerve injuries derived from trauma is about 300,000 cases per year. Moreover, nerve injuries are an important component of traumatic limb amputations, with an incidence of 2/100,000 persons per year described for hand amputations. Therefore, repair and regeneration of peripheral nerve injuries represent a major field where clinical application of innovative therapies in regenerative medicine should be sought.
Peripheral nerve fibers are able to regenerate and lead to functional recovery provided that an
appropriate milieu and guide is available. However, the clinical outcome of neural repair after
extended substance loss after nerve injury is often unsatisfactory and therefore innovative strategies for improving the outcome after neural damage are in demand.
The main objective of the BIOHYBRID project is the development of a regenerative therapy using an innovative biohybrid artificial nerve device with the goal of repairing damaged nerve trunks. The work program includes an integrated experimental approach bringing together the main aspects of regenerative medicine: a) reconstructive microsurgery, b) regenerative scaffolds and c) transplantation. This approach will allow the biological pre-fabrication of biohybrid nerve devices, their transplantation into nerve gaps in various animal models and the comprehensive evaluation of the regenerative outcome. The SME involvement, for the first time in this biomedical field, will not be limited to production and supply of materials and services but includes also active participation in the conduction of the experiments for in vivo preclinical assessment and follow-up. Based on the extensive basic and clinical experience within this consortium a biohybrid artificial nerve device will be developed together with standardised application and evaluation parameters. A key objective of this study will be to generate, for the first time, a protocol that can serve as a template for future clinical trials in the regenerative therapy of damaged peripheral nerves. The BIOHYBRID project with its consortium partners combines excellent expertise to successfully reach the objectives and stands therfore on the front line of regenerative medicine approaches.The conceptual framework for the proposed project could be summarised as in the following schematic drawing:
Development of innovative biohybrid artificial nerve.
We are looking for the production of a bio-inspired and bio-active nerve graft device, e.g. an artificial organ which not only passively substitutes the damaged nerve tissue but also activates the biological processes inside the receiving tissue (bio-activation). As shown in the figure above, we aim to promote the regeneration process through various strategies: (1) Creating a construct – with optimal porosity and layers degrading at a programmed rate – which activates the biological repair process by its 3D-structure formed by a hydrogel or nanofibres; manipulating the main properties of the construct (e.g., length, diameter, rigidity, permeability, degradability, interior surface morphology, luminal constitution, etc.) in order to meet the clinical requirements; in particular, the components which are most suitable to promote nerve regeneration are cells (especially glial cells) and bio-active molecules (such as neurotrophic factors) that are main players in the degeneration/regeneration scenario after nerve injury; the artificial nerve guide device can thus be enhanced with the enrichment of supportive cells and exogenous neurotrophic factors into the lumen. A neurotrophic factor delivery system and/or preformed instructive neurotrophic factor gradients should be part of the biohybrid artificial nerve in order to provide temporally optimised neurotrophic factor supply. Transplantation of supportive cells further creates the potential to induce the synthesis of various factors which are important for the activation of biological regeneration processes through gene transfer.