Axona+P3:P19l guidance using 3D bioprinting of rationally designed hydrogels
Nerve injury repair remains a challenge to modern medicine. Up to 300,000 peripheral nerve injuries happen in Europe every year (Mohanna, 2003). Despite good surgical advances, complete success in motor reinnervation is still limited with loss of function of donor site in autografting (Ray, 2010) and miswiring of regenerating nerves or synkinesis resulting to uncoordinated muscular movements and poor functional outcome (De Medinaceli, 1987). Accurate and timely reinnervation is particularly important in highly specialised surgical procedures such as transplantation of complex organs like face, limb, or larynx.
Among biomaterials reported for regenerative medicine, hydrogels hold huge potential as being structurally similar to extracellular matrix and processed in relatively mild conditions (Rufaihah, 2015). However, a major limitation in tissue engineering is delivery of nutrients and extraction of waste in the complex construct.
Implantable scaffolds beyond 200?500 ?m in thickness, for example, must be accompanied by host angiogenesis in order to provide adequate nutrient/waste exchange in the newly forming tissue (Kumar, 2015).
I have been part of the team in Bristol University who developed a rationally designed peptide-based self-assembling fibres (hSAF) which allow coupling of molecules that influence neuronal cell differentiation and behaviour (Banwell, 2009; Mehrban, 2014). The hSAF hydrogels are made up of natural amino acid residues which overcome the problem of disease transmission, unwanted immune response, and non-biodegradability. Recently, a group in Cardiff University tried the same hSAF hydrogels in neural stem cells and confirmed what I have established in my MD project in Bristol University that these ?intelligent biomaterials? hold a promise in overcoming the limitations in current approaches to nerve-tissue repair (Mehrban, 2015).
On a macro level, fabrication of clinically relevant complex multicellular tissues and organs is a huge architectural challenge since cells and other bioactive compounds need to be precisely arranged in three-dimensional scaffolds while maintaining structural support. Advances in medical engineering employ 3D bioprinting technology to generate spatially-controlled cell patterns and biologic three-dimensional constructs. Fortunately, Swansea University has pioneering works in bioprinting technology and is a recognised leader in this field (Rees, 2015).
In this study, I intend to combine the wealth of knowledge on peptide nanofibre formation and biomimetic functionalisation developed in Bristol University, neural stem cell engineering strategies established in Cardiff University and University College London with world-class bioprinting technology and technical skills on regenerative medicine in Swansea University, to create a vascularised nerve construct as artificial nerve channels. This collaborative project is a continuation of my previous successful studies on material science in pursuit of closing the gap between the bench and bedside and bringing forward translational research findings to clinically significant constructs.
Objective: To engineer a hydrogel that can guide the direction of regenerating axon tips to a specified course thereby guiding them to appropriate distal endoneural tube regeneration.