Microfuidic devices and three dimensional-printing strategies for in vitro models of bone

Abstract

Bone is a complex and highly dynamic tissue, which has been worldwide studied, from fundamental biology to tissue engineering fields. Even so, current in vitro models do not truly replicate the native bone tissue environment. For so, new and improved in vitro tissue models are necessary to obtain more reliable data, not only in a development point of view, but also to fasten the translation of new drugs into the clinics. In this reasoning, tissue-engineering strategies were applied to develop mimetic and three-dimensional (3D) microenvironments, which were associated with microfluidic devices for the development of more complex and realistic systems. Such devices mimic blood vessels that are present in the native tissue, thus enabling the study of complex biological mechanism as such as bone angiogenesis. More recently, 3D printing has been pursued to produce more intricate microfluidic devices and engineered tissues in a single step. The ability to print spatially controlled structures composed of different biomaterials, growth factors and cells caught the attention of scientists for the development of more efficient in vitro models. Additionally, it allows obtaining microfluidic devices and/or engineered tissues with the desired architecture within a small amount of time and with reduced costs. Recently, the use of high-resolution scanning boosted the production of patient-specific implants. Despite the difficulties associated with 3D printed structures that still need to be overcome, it has been proven to be a valuable tool to accomplish a new generation of 3D bioprinted bone-on-a-chip platforms.The authors thank the funds obtained through the FROnTHERA (NORTE-01-0145- FEDER-0000232) project supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). FRM acknowledges Portuguese Foundation for Science and Technology (FCT) for her post-doc grant (SFRH/ BPD/117492/2016), JMO thanks FCT for the distinction attributed under the Investigator FCT program (IF/01285/2015) and VMC acknowledges Investigator FCT program (IF/01214/2014)