Periodic Reporting for period 3 - MOZART (MesopOrous matrices for localiZed pH-triggered releAse of theRapeuTic ions and drugs)
Reporting period: 2018-11-01 to 2019-10-31
5-10% of the overall fractures result in a delayed bone healing or in a non –union fracture. The current clinical approach is not always successful and patients may suffer from extra surgeries and may experience disability and pain.
The strategy proposed in MOZART to solve these problems is the introduction of a local, dual ion/drug release smart system into the injured site to improve the therapy. Hence, the objective of the MOZART project is to develop a library of innovative nanomatrices (NMs) to be used as a smart platform technology for effective, highly targeted therapies in the biomedical field. The developed NMs are characterized by innovative compositions containing several therapeutic ions able to elicit a specific biological response and also by the presence of a high volume of nanopores that can be exploited to upload a specific payload.
The advantages of such a treatment include a synergistic effect between ions and biomolecules released from the biomaterial, high delivery efficiency, continuous action in situ, fine control of the amount of therapeutic agents incorporated (and released), reduced toxicity and overall convenience to the patients. In order to vehicle the NMs in the surgical site avoiding their dispersion, a thermosensitive, resorbable and injectable gel has been developed. As proof of concept, the MOZART project had addressed two well-defined and global clinical challenges, i.e. non-healing bone and chronic non-healing skin wounds, developing two different medical devices.
In such pathological states, with particular reference to wound infection, an endogenous pH value change due to inflammatory or hypoxic conditions was found to be present, with niche of both acidic and basic pHs and has been used to trigger the drug release. In MOZART the synergistic release of ions and drugs has been exploited to demonstrate the potential for a radical improvement in therapy for those patients with chronic skin wounds that fail to heal and bone healing defects that resist conventional therapy. Both these fields involve a very large patient numbers which are increasing with an ageing population.
Detailed cost estimations have been made for each material and include the costs of chemicals employed in the synthesis (precursors, templating agent, solvent etc), energy consumption during each process, waste management (disposal of solvents or solid garbage etc.), sterilisation and packaging of the MOZART devices. Product scalability is not the only factor in industrial applications, it is also important to maintain efficiency in cost and resource usage. Safety consideration have been constantly considered as well as standards and regulatory matters.
15 papers have been published in international Journals with high impact factors and other two have been submitted before the end of the project. Two workshops have been organised, one for a more scientific audience and the second one for the industrial community.
MOZART NMs have been translated to TRL5 using a robotic cell developed able to produce 500g/day (TRL5) compared to 1g/day (TRL3). In such a way, a safe and resource efficient manufacturing process has been developed, filling the gap between academic and industrial settings concerning the production of these nanomaterials, in terms of industrial and regulatory standards.