WP3: Materials formulation and functionalization
Task 3.1: Development of the engineered hydrogel (PISAS)
The preparation conditions have to lead to a stable hydrogel layer showing:
- a good biocompatibility;
- a Young’s modulus of ~ 1 kPa, in order to match the stiffness of nerve tissue;
- the possibility to covalently attach them to the polyimide surface.
The hydrogels will be based on:
- zwitterionic polymers;
- 2-oxazoline polymers.
Both these materials have currently been considered to outperform the well-known poly(ethylene glycol) in in vivo applications, in terms of both stability and performance. PISAS has a strong experience with both polymers.
Task 3.2: Degradable linkers and drug embodiment (PISAS)
This task will be centered on the development of degradable linkers within the hydrogel matrix to allow incorporation of neurotrophic factors (NGF, GDNF, etc.) - in order to promote neural migration and axonal health - and anti-inflammatory factors (VES, IL-10, etc.) – in order to suppress the inflammatory reaction leading to fibrotic overgrowth and deterioration of the functionality of the electrode. The controlled release of neurotrophic and anti-inflammatory factors from a hydrogel covalently attached to the polyimide surface will be achieved by employing biodegradable linkers being a part of the hydrogel structure. Two main types of linkers will be developed:
- GFLG peptide linkers:
As a first option, an oligopeptide linker will be used for the controlled release of a drug by enzymatic degradation of peptide bonds. The kinetics of the release depends on the aminoacid sequence used. For example, the enzymatic degradation of a GFLG peptide used for conjugation of doxorubicin can be completed within 30 hours.
- Aliphatic polyester linkers:
The second option is represented by biodegradable aliphatic polyesters. It was reported previously that macromonomers based on aliphatic polyester are suitable for preparation of nanoparticles with tunable degradation. This work shows that the time of biodegradation is dependent on the monomer type and on the length of the chain. Degradation time increases in the following order: polyglycolic acid (PGA) < polylactic acid (PLA) < polycaprolactone (PCL) from few hours to more than one month. Linkers with different degradation times will be prepared and tested
Task 3.3: Ex vivo tests: hydrogel stability (SSSA)
In order to evaluate the stability of the above coatings, SSSA will perform ex vivo tests on explanted rat peripheral nerves. During these tests, polyimide substrates coated with the engineered hydrogels will be inserted in explanted animal tissues, closely resembling the procedure that will be followed during in vivo tests. Afterwards, the sample will be extracted and the coating analyzed by optical microscopy and Fourier Transform-Infrared (FT-IR) methods, to assess if its integrity will be compromised by the insertion.