Abstract

A Microfluidics-based Approach to Tackle Bone Tumors: Towards New Materials for Bone Metastases

Gabriela Graziani, Assistant Professor, Politecnico di Milano

Tumor relapse after surgical excision of bone metastases poses a key unmet challenge in orthopedic oncology due to its high incidence rate and potentially fatal outcome. Even in advanced cancer state, patients undergo treatment with bone substitutes/implants, to fill gaps resulting from excision surgery. In this groundbreaking study, we propose novel antitumor metal-based coatings to functionalize implanted devices and prevent tumor relapses. For their design and validation, we use a microfluidic-based approach, where chips are designed to select the optimal concentration of metal. To achieve this, we designed and realized a gradient generator microfluidic device, to be used for both tumor (breast cancer cells that metastasize in bone, MDA-MB-231) and healthy cells (mesenchymal stem cells, MSCs). This enables the detection of the optimal concentration for antitumor efficacy while avoiding cytotoxicity. In the chip, cell chambers are designed for cell seeding in a medium (2D configuration) and in a biomimetic gel (3D configuration) for pre-screening and validation, respectively. Coatings, manufactured by Ionized Jet Deposition, are dissolved in a simulated medium to obtain the solution to inject in the device. Cell viability, proliferation and migration are measured by calcein staining and fluorescence microscopy analyses in 6 parallel columns of chambers, each receiving a different dilution of the active compound. Three chambers per column allow for obtaining replicates simultaneously. Results demonstrate that the gradient generator microfluidic can detect the effect of different concentrations of the eluates on cells viability, migration and proliferation, with the latter parameters significantly more affected by metals. Hence, by merging results on MSCs and MDA, the device enables a fine selection of the metal concentration to be used. Cellularised biomimetic gels (collagen and Matrigel based) can be injected into the chambers without creating defects or hampering cell visualization. This new approach appears promising for the design of coatings, and can be easily  transferred to validate different biomaterials.