- Develop advanced synthetic-natural biohybrid materials with improved biocompatibility and biodegradability (18 – 24 months), regenerative capacity (nerve gaps > 3cm) and mechanical properties (≈ 11.7 MPa) suitable for the generation of 3D micropatterned structures comprising with selective porosity and controlled degradation. Determine the optimal physical parameters required by biomimetical endoneural tubes to pave for an efficient regeneration of both sensory and motor axons. Scale – up biomaterial production to industrial levels
- Develop advanced manufacturing technologies for the generation of biomimetic endoneural tubes with precise morphologies and sizes (intraluminal microchannels or fibers with high aspect ratio). Scale – up manufacturing technologies to industrial levels
- Understand the interplay between scaffolds and the endothelial cells, the Schwann cells and neurons (via in vitro assays) to promote the generation of Bands of Büngner and revascularization inside the Implantable nerve guidance conduits (INGCs), and provide the trophic and tropic conditions for an optimal axonal regeneration and remyelination.
- Design, fabricate and optimize a new generation of Neural Guides composed of two clearly differentiated parts:
i) An outer wall with selective porosity for nutrient exchange and a slow-degrading degradation ratetax to reduce fibrosis, to protect the newly formed nerve cord, and to provide physical stability that avoids the INGC collapse while regeneration progresses;
ii) An innerendoneural-like microstructure to provide a topographical axonal regeneration. This part will be composed of a biomaterial with a regulated degradation tax according to the repaired gap length, being replaced once the Bands of Büngner and the axons have regenerated across the INGC. Afterwards, the system would behave as a natural interstump reconnecting nerve cord, and thus avoid secondary compressive damage of regenerated axons.
- Characterize, in a clinically relevant animal model of sciatic nerve injury, the performance of the produced INGCs for key parameters such as the maximum gap length that can be repaired, their ability to promote the regeneration of both motor and sensory axons, and their ability to pave for precise target reinnervation with as resulting in improved functional recovery. Comparison to regenerative capacity of autografts.
- Scaled up production of the new generation of INGCs taking into account standards, regulatory affair and economical issues. Exploitation plan.