Engineering Amyloid Fibrils for Nanotechnology and Neuronal Cell Regeneration

Biomaterials based on self-assembling peptides are promising in the development of different therapeutics in regenerative medicine. Peptide scaffolds are a network of nano fibers that mimics the natural extracellular matrix much superior to microfiber based polymer scaffold. The limited regenerative capacity of the brain in neurodegenerative diseases is due to the loss of the neural extra cellular matrix (ECM) to promote cell division and remodeling of tissue. Stem cell transplantation holds promise as a therapy but it must be given suitable biochemical and contact mediated cues so that they suitably develop to restore functional tissue. Here, we report the development of an amyloid inspired small peptide based hydrogel, designed and based on α-synuclein protein, where hydrogel formation is triggered by different stimuli such as heating/cooling or changes in pH. The peptides reflect cross-β sheet rich amyloid and assemble into a nano-fibrous meshwork mimicking the natural extra-cellular matrix that helps in the differentiation of stem cells towards neuronal lineage without the addition of any growth factors. Amyloid hydrogels are thixotropic and provide bio-mechanical cues to promote differentiation of mesenchymal stem cells towards neurons. In the current study, when we implanted amyloid hydrogel in the rat brain via minimally invasive surgery, we observed that the inflammatory response is comparable to sham control. We also performed a 3D culture of mesenchymal stem cells with the hydrogel, harnessing its thixotropic behavior and finally studied the efficacy of the amyloid hydrogel as a vehicle for successful stem cell transplantation in a Parkinsonian animal model. When hMSCs were implanted in Parkinsonian mouse model with this amyloid hydrogel, the hydrogel not only supports the survival of the hMSCs but also promoted the stem cell differentiation towards neuronal lineages. Amyloid hydrogels could also be used for encapsulating various growth factors and culture cells in 3D for optimal differentiation. Our data suggest the suitability of the present class of hydrogel for neuronal tissue engineering applications and could, therefore, be used for development of stem cell based therapeutics against neurodegenerative diseases like Parkinson’s disease.