Spinal Cord Injury Engineering Success
The following flow chart demonstrates the Spinal Cord Injury Subgroups methodology in approaching the problem of understanding the microenvironment of the lesion and how we would apply our scaffolding in order to achieve axonal regrowth.
Bioprinting Engineering Success
The Bioprinting Engineering success served to demonstrate the different decisions we took whilst ensuring we were tackling and solving our project problems. We demonstrate how we integrated our research into our engineering design cycle to ultimately build and test our scaffold design through the use of relevant simulations.
MFP Engineering Success
The Mussel Foot Protein Engineering success flow map serves to demonstrate our engineering decisions we had to take, ensuring we were tackling and solving our project problems. We demonstrate how we integrated our research into our engineering design cycle to explore the engineering of our synthetic biology approach incorporating recombinant Mussel Foot Protein PvfP-5β.
Design of Protocols
We developed these protocols to demonstrate how we would design our experiments and evaluate the outcomes that may arise. We will implement these protocols next year in Phase Two to further validate our proposed implementation. In addition to designing our experiments, we have concluded how we would evaluate the outcomes, deal with unexpected results and planning further steps including in vivo studies.
A PDF handbook has been created for all our protocols.
Future Engineering Improvements
Drug Delivery System
Novel therapeutics research has mainly focused on the delivery of pharmacological compounds, known as Drug Delivery System (DDS). Drugs can be delivered systematically, affecting the whole body, or locally. Local delivery results in better achievements, as it represents a way to decrease side effects of drug toxicity as well as maximising the effectiveness of the treatment. The development of a successful drug delivery nanosystems results in the scaffold having beneficial neuro-protective and neuro-regenerative effects.
Because of properties such as nontoxicity and biodegradability, PCL has been very popular in the field of drug delivery. Numerous drugs have already been incorporated in PCL scaffold, in the form of nanoparticles or nanofibers. Although, current fabrication of a 3D printed porous scaffold including drug delivery system has not been developed. Taking this into account, if we were to include a DDS into our project some drugs which we would particularly investigate would be melatonin and dexamethasone acetate. Melatonin is a versatile hormone with many properties such as antioxidative, antiapoptotic, neuroprotective, and anti-inflammatory. Different studies have suggested the restoration of neurologic functions after SCI, involving mechanisms such as antioxidant effects, regulation of iNOS, inhibition of proinflammatory cytokines, blood vessel repair, restoration of the blood-brain barrier, inhibition of cell apoptosis, edema resistance and inhibition of cell autophagy. As well as melatonin, dexamethasone acetate it’s known to have neuroprotective effects by inhibiting lipid peroxidation and inflammation due to the reduction of cytokine release and expression. However, it has some limitations caused by its hydrophobicity, biocompatibility and numerous side effects if using large dosage.
Implementation of Stem Cells
In order to further investigate axonal regrowth, stem cells can be implemented alongside our scaffold design. We have researched different stem cells, particularly mesenchymal (MSCs) and neural stem cells (NSCs). These are effective as MSCs are easy to isolate and do not raise any ethical concerns (Cofano et al.,2019), whilst NSCs show evidence of promoting neural differentiation and synaptogenesis in scaffoldings (Shrestha et al., 2014). You can learn more about the proposed implementation of both these stem cells in the SCI Pathophysiology page.
- Angela Faccendini et al. (2017) ‘Nanofiber Scaffolds as Drug Delivery Systems to Bridge Spinal Cord Injury’, Pharmaceuticals, 10(4), p. 63. doi: 10.3390/ph10030063.
- Cofano, F., Boido, M., Monticelli, M., Zenga, F., Ducati, A., Vercelli, A., & Garbossa, D. (2019). Mesenchymal stem cells for spinal cord injury: Current options, limitations, and future of cell therapy. International Journal of Molecular Sciences, 20(11), 2698.
- Shrestha, B., Coykendall, K., Li, Y., Moon, A., Priyadarshani, P., & Yao, L. (2014). Repair of injured spinal cord using biomaterial scaffolds and stem cells. Stem Cell Research & Therapy, 5(4), 91.
- Wang, Y. et al. (2017) ‘Effective improvement of the neuroprotective activity after spinal cord injury by synergistic effect of glucocorticoid with biodegradable amphipathic nanomicelles’, Drug Delivery, 24(1), pp. 391–401. doi: 10.1080/10717544.2016.1256003.
- Wong, B. S., Teoh, S.-H. and Kang, L. (2012) ‘Polycaprolactone scaffold as targeted drug delivery system and cell attachment scaffold for postsurgical care of limb salvage’, Drug Delivery and Translational Research, 2(4), pp. 272–283. doi: 10.1007/s13346-012-0096-9.
- Zhang, Y. et al. (2018) ‘Melatonin for the treatment of spinal cord injury’, Neural Regeneration Research, 13(10), p. 1685. doi: 10.4103/1673-5374.238603.