An in vitro and ex vivo model of biomimetic regenerative devices to treat bone metastases and soft tissue tumors: BIOBOS PROJECT (Moh GR-2016-02364704)

Biobos is a project funded by Italian MoH GR-2016-02364704 Other Italian Institutes involved: Istituto Ortopedico Rizzoli, Bologna CNR, Faenza

The hypothesis of BIOBOS is that the development of nanostructured biomimetic materials medicated with a chemotherapeutic drug and with one used for tissue regeneration will be an innovative strategy to be integrated with the current multidisciplinary treatment options on patients with bone metastases from breast cancer and on patients with soft tissue sarcomas. Three types of medicated materials have been developed: i) porous scaffolds and ii) self-regulating biomimetic pastes (bone cements) with anti-osteoporotic functions to be applied in the future in patients with bone metastases; both materials were functionalized with the standard chemotherapy doxorubicin, and an anti-RANKL antibody, which by blocking osteoclast differentiation, helps tissue regeneration in lytic-type metastases; iii) polymeric nanofibrous tissue-nonwoven mesh functionalized with the chemotherapeutic epirubicin and the anti-inflammatory diclofenac, used to evaluate its regenerative potential. After the synthesis and characterization of the materials, the functionalization of the drugs at optimal concentrations for local release was optimized for the bone cements and for the meshes, so as to have the release of the chemotherapeutic and subsequently of the regenerative drug. Meanwhile, on non-medicated materials, the monoculture and coculture conditions of tumor cells (of breast cancer for bone metastasis applications; an epithelial sarcoma cell line for application on sarcomas) and stromal cells (osteoclasts and osteoblasts for applications on bone metastases, a cell line of healthy murine fibroblasts for application on sarcomas. For both pathologies, after approval by the Local Ethics Committee, biological samples were collected to test the ex vivo efficacy of the materials medicated on explants or primary cultures.