In pathological situations, where bacterial infection is a common, often highly serious complication (e.g. osteomyelitis following bone reconstructive surgery and infected chronic wounds), conventional treatments include systemic antibiotic administration, surgical debridement, wound drainage and implant removal (if present). The over-use of antibiotics (with the development of antibiotic resistance) is a world-wide problem hence the drive for alternative antimicrobials is a must.
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.