Development of Biomaterials for Neural Tissue Engineering

Abstract

Tissues are the building blocks of organs, comprised of cellular and acellular components. The acellular extracellular matrix (ECM) acts to simultaneously provide biological and physical support to cells and drive tissue function. The complex interconnected nature of biochemical & physiomechanical features of human tissue enables maintenance of dynamic architectures, capable of supporting function throughout human lifetimes. When we consider the incredible structural and functional complexity of the human brain, we can only infer that the interconnectedness of features is even more delicately balanced. Recreating complexity of the human CNS in the form of model systems is an invaluable tool for furthering scientific knowledge, in areas including tissue development, pathogenesis, and therapeutic testing. Improved in vitro modelling of the human brain is a particularly powerful tool when we consider the unsuitability of existing models and severity of unmet clinical needs i.e. distinct lack of treatments for neurodegenerative disease. Development of advanced in vitro models of the human CNS is hampered by obscurity surrounding neurophysiology and pathogenesis, particularly the importance of the ECM. Researchers now recognise a multidisciplinary approach is necessary to understand and reproduce complexity of the CNS, utilising biology, chemistry, physics, mathematics, engineering & other fields i.e. material science to develop “soft solid” hydrogel biomaterials to mimic mechanical behaviour of the brain. This project looks to enable engineering of neural tissue via development of hydrogel biomaterials that are capable of mimicking structural and architectural complexity of the CNS. Research here demonstrates suitability of HAMA hydrogels for neural tissue engineering, with biological relevance of HA/laminin components and retained cell viability, alongside replication of biomechanical properties of the CNS. Novelty of work herein arises from the balancing of biological and mechanical properties to develop a tuneable hydrogel system, highlighting potential for further tailoring via additional biofunctionalisation or structuring via bioprinting.