Speaker
Description
Introduction:
Cancer is one of the leading causes of death worldwide and although developing new therapies can help fight this disease, cancers which origins from breast, lung or prostate can undergo metastasis process leading to development of secondary tumors in other parts of the human body [1]. Bone is the organ to which cancer often metastases and to pioneer cancer therapies, creation of functional bone tissue models is crucial. Several studies aimed at understanding this process have already been conducted using cell cultures and/or animal models. These include basic 3D tissue models representing bone, blood vessels, and cancer. Yet, both 2D and 3D in vitro models have their limitations and currently there are few functional bone in vitro models fully reflecting hierarchical structure of the bone [2]. Here, we propose a new 3D bioprinted perfusable bone model as a promising tool for study cancer metastasis to bone.
Methods:
The developed bioprinted perfusable bone model is consisting of three different compartments, each one built from different materials and reproducing subtissues of the bone: GelMA with β-TCP (calcified region of the bone), GelMA (bone/vessel interface) and fibrin with alginate (vessel). Extrusion bioprinting was used for fabrication of the structures of the model and for verification of obtained structures in perfusion environment the commercially available bioreactor chamber (Polbionica, Poland) was used. The structural, chemical and mechanical properties of obtained bioinks were investigated by FTIR, SEM and microscope imaging as well as degradation and swelling studies. Additionally, for further research the CFD studies were provided in order to optimalize the thickness of printed structures and their distribution inside the bioreactor chamber for future optimal cell seeding and bioprinting with cells. Moreover, as the proof of concept, the simulation studies in what way circulating tumor cells behave in the vessel’s lumen of the fabricated perfusable bone model were provided revealing how possibly secondary tumor can develop in the bone.
Results:
All of the prepared bioinks display a proper rheological behavior, making it possible to overcome the negative effects affecting viability of the cells during bioprinting. SEM images allowed to conclude that total porosity and the size of the pores are suitable for cell proliferation. Calculated printing accuracy from microscope images of printed structures revealed that extrusion bioprinting may be successfully applied for creation of such models. The CFD studies allowed to optimize distribution of the printed structures as well as put insight into cancer cells attachment depending on fluid flow inside perfusable blood vessel leading to conclusion what parameters are potentially crucial for secondary tumor development. The presented results add important insight into fabrication parameters as well as optimalization for creation of perfusabale tissue models. Therefore, the proposed 3D bioprinted bone model can be successfully considered for cancer metastasis studies.
References:
[1] Salvador, F. et al. „From latency to overt bone metastasis in breast cancer: potential for treatment and prevention.” J. Pathol. 2019, 249, 6–18.
[2] Tang, D., et al. "Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration." Biomaterials 2016, 83, 363–382.