Objective 1: In the first phase of the project, the best technological solutions for the production of polymeric electrospun scaffolds of different geometry, fiber diameter and chemical composition have been studied together with the compatibility of conjugation process with 2 drugs (anti-inflammatory and pro-myelinating agent). In the second phase, various conjugation strategies were developed, based on blending processes and chemical conjugation of molecules and polimers. The analytical techniques for measuring drug concentrations were then validated and the release curves from the functionalized scaffolds were defined, leading to the production of electrospun polymeric fibers functionalized with the drugs, having a release kinetic compatible with the expected results. Therefore, in vitro tests on cellular systems that have been validated for the screening of the anti-inflammatory and pro-myelinating activity of the compounds are underway. The last phase of the project involves the implantation of the optimal solution for release kinetics and biological effect, in rat spinal cord contusion model, standardized for the lesion volume and locomotor parameters. The industrial scalability of the optimized electrospunning technique of the "scaffold", therefore considered as a "medical device", will be tested at RiMos company; the industrial scalability of the "scaffold" conjugation process with pharmacologically active molecules, thus considered as "advanced therapy/drug product", will be tested at ValPharma. In vitro toxicity tests of "scaffolds" will be performed according to the Good Laboratory Practice (GLP) regulations at the TransMed Research company.
Objective 2: A system for assessing the evidence-based rehabilitation pathway will be developed and validated. These demonstrators will allow an evaluation of the evidence-based rehabilitation pathway to support existing clinical scales and to the degree of injury and neurological picture (ASIA scale). We will pursue a simple and accurate set-up to provide immediate and objective feedback to the operator: a mere natively digital reference represents a major advantage over the clinical evaluation of current locomotor performance. In order to develop methods and data processing algorithms from inertial sensors in the injured subject, the data acquisition activity is ongoing at the Montecatone Rehabilitation Institute. In particular, in order to validate the inertial measurements for the estimation of space-time parameters of the step, of the articular kinematics of the lower limbs during gait and the mobility of the trunk, acquisitions were carried out in which the sensors were coated with stereophytogrammetric shots during functional tests. In addition, test-retest was performed to determine intra-operator reliability and repeatability of the measurements during "10-m walk test" and "6-min walk test". Inertial sensor data was also collected during waterborne tasks. Developed algorithms will allow a useful report to support diagnosis in relation to lesion and neurological scale (ASIA scale) and to more accurately define the rehabilitation pathway.
