Bioengineering-enhanced neurosurgical solutions

The advancements in basic sciences and the availability of sophisticated technological aids have led over the last few years to the rise of innovative surgical strategies, the identification of better prognostic/predictive biomolecular factors, and the development of novel drugs all meant to profoundly impact the outcome of neurosurgical patients. This thesis touches upon the window of opportunity to exploit bioengineering techniques in three subspecialties of this vast discipline: neuro-oncology, radiosurgery and neuro-traumatology. After a thorough identification of some unresolved clinical problems and the limits of current management strategies in those areas, some technical solutions are proposed and defined from either experimental hypothesis or clinical research investigations. The neuro-oncology section presents the exciting topic of nanodrugs for adjuvant chemotherapy in high-grade gliomas, the most aggressive primary brain tumours. The use of hyaluronic acid nanoshells is proposed to encapsulate prodrugs and exploit the mechanisms of interaction between glioma cells and hyaluronic acid, a natural component of extracellular matrix. The theoretical advantages of this approach are discussed with details regarding the possible scalability of this technique to increase the efficacy and biodegradability of other molecules suitable as contrast media for neuro-imaging and radiotracers for nuclear medicine investigations. The radiosurgery section in fact continues the previous one, highlighting the rationale for further implementation of radiosurgical protocols thanks to nanoshell-encapsulated radioenhancers and multi-imaging fusion protocols. Experimental data on the optimization of radiosurgical plans for artero-venous malformations close to the motor strip or basal ganglia are presented, demonstrating the dramatic reduction in radiation dose to the pyramidal tract and supporting the anticipated benefits in terms of radioprotection, and avoidance of post-radiosurgical deficits. Finally the neurotrauma section presents the clinical results from a prospective study on an innovative device for non-invasive monitoring of intracranial pressure, a tool that given the high reliability demonstrated in this research might find a role in preclinical or neurointensive care settings and reduce the need for serial neuroimaging in traumatic brain injured patients. The last chapter concludes this thesis duly outlining some forecasts and supporting literature for the widespread application of bioengineering enhanced solutions in neurosurgical theatres, wards or outpatient clinics.