Bionic implants are widely used to replace or restore impaired neurological functions.
However, they normally rely on stiff metallic electrodes, which can trigger inflammatory
responses hindering long-term device performance. Although different material and form factor design strategies have been explored, the establishment of a chronically stable device-tissue interface remains challenging. It has been proposed that tissue-engineered coatings composed of hydrogel matrices embedded with neural cells could enhance the biointegration and hence long-term performance of implantable electrodes. Furthermore, establishing synaptic connectivity between the implant and the host tissue would enable novel and more biomimetic mechanisms of tissue neuromodulation. However, the lack of
biomaterials able to support the development of functional neural networks hinders the
implementation of these 'living electrode' constructs.
This thesis aimed to design a biosynthetic hydrogel carrier with key physicochemical
cues to guide the development of primary neuroprogenitor cells into functional neural
networks. To investigate the influence of cell-material interactions in neural development,
neuroprogenitor cells were encapsulated in hydrolytically degradable poly(vinyl alcohol)
(PVA) hydrogels functionalised with low amounts (10%) of sericin and gelatin (PVA-SG).
The results indicated that the limited biological content and the restrictive polymer network impaired the growth of encapsulated astrocytes, which in turn hindered neural
development. Therefore, an enzymatically degradable PVA-gelatin hydrogel (PVA-GEL) with tuneable mechanospatial properties was developed. By systematically varying the
gelatin content from 0 to 100%, it was found that only hydrogels with greater than
50% gelatin could promote the growth of encapsulated primary mature astrocytes while
maintaining mechanical stability. Furthermore, neuroprogenitor cells co-encapsulated with
mature astrocytes in PVA-GEL hydrogels were able to grow into synaptically active neural
networks. Finally, PVA-GEL hydrogels were shown to interface with and support the
ingrowth of brain tissue ex vivo, highlighting their potential in the design of biointegrative
electrode coatings for more efficacious and longer-lasting bionic devices.